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Relevance of Twitter.com forthcoming Payment System for Scientific Content Promotion and Monetization

Highlighted Text in BLUE, BLACK, GREEN, RED by Aviva Lev-Ari, PhD, RN

GIASOURCEN M. VOLPICELLI

Gian M. Volpicelli

SENIOR WRITER

Gian M. Volpicelli is a senior writer at WIRED, where he covers cryptocurrency, decentralization, politics, and technology regulation. He received a master’s degree in journalism from City University of London after studying politics and international relations in Rome. He lives in London.

SOURCE

https://www.wired.com/story/twitter-crypto-strategy/

 

BUSINESS

APR 5, 2022 7:00 AM

What Twitter Is Really Planning for Crypto

The duo behind Twitter Crypto say NFT profile pics and crypto tipping are just the beginning.

 

YOU MIGHT HAVE heard of crypto Twitter, the corner of the social network where accounts have Bored Apes as profile pictures, posts are rife with talk of tokens, blockchains, and buying the Bitcoin dip, and Elon Musk is venerated.

Then again, you might have heard of Twitter Crypto, the business unit devoted to developing the social network’s strategy for cryptocurrency, blockchains, and that grab-bag of decentralized technologies falling under the rubric of Web3. The team’s unveiling came in November 2021 via a tweet from the newly hired project lead, Tess Rinearson, a Berlin-based American computer scientist whose career includes stints at blockchain companies such as Tendermint and Interchain.

Rinearson joined Twitter at a crucial moment. Jack Dorsey, the vociferously pro-Bitcoin company CEO, would leave a few weeks later, to be replaced by CTO Parag Agrawal. Agrawal had played an instrumental role in Bluesky, a Twitter-backed project to create a protocol—possibly with blockchain components—to build decentralized social networks.

As crypto went mainstream globally and crypto Twitter burgeoned, the company tried to dominate the space. Under the stewardship of product manager Esther Crawford, in September 2021 Twitter introduced a “tipping” feature that helps creators on Twitter to receive Bitcoin contributions through Lightning—a network for fast Bitcoin payments. In January, Twitter allowed subscribers of Twitter’s premium service, Twitter Blue, to flaunt their NFTs as hexagonal profile pictures, through a partnership with NFT marketplace OpenSea.

Twitter Crypto is just getting started. While Rinearson works with people all across the company, her team is still under 10 people, although more hires are in the pipeline, judging from recent job postings. So it’s worth asking what is next. I caught up over a video call with Rinearson and Crawford to talk about where Twitter Crypto is headed. 

The conversation has been edited for clarity and brevity.

WIRED: Let’s start with the basics. Why does Twitter have a crypto unit?

Tess Rinearson: We really see crypto—and what we’re now calling Web3— as something that could be this incredibly powerful tool that would unlock a lot for our users. The whole crypto world is like an internet of money, an internet of value that our users can potentially tap into to create new ways of owning their content, monetizing their content, owning their own identity, and even relating to each other.

One of my goals is to build Twitter’s crypto unit in such a way that it caters to communities that go beyond just that core crypto community. I love the crypto Twitter space, obviously—I’m a very proud member of the crypto community. And at the same time, I recognize that people who are really deep in the crypto space may not relate to concepts, like for instance blockchain’s immutability, in the same way that someone who’s less intensely involved might feel about those things.

So a lot of what we try to think about is, what can we learn from this group of people who are super engaged and really, really, creative? And then, how can we translate some of that stuff into a format or a mechanism or a product that’s a little bit more accessible to people who don’t have that background?

How are you learning from crypto Twitter? Do you just follow a lot of accounts, do you actually talk to them? How does that learning experience play out?

Esther Crawford: It’s a combination. We have an amazing research team that sets up panel interviews and surveys. But we’re also embedded in the community itself and follow a bunch of accounts, sit on Twitter spaces, go to conferences and events, engage with customers in that way. That’s the way the research piece of it works. But we also encounter it as end users: Twitter is the discovery platform today for all things crypto.

One of the things we do differently at Twitter is we build out in the open. And so this means having dialog with customers in real time—designers will take something that is very early-stage and post it as a tweet and then get real-time feedback. They’ll hop into spaces with product managers and engineering managers, talk about it live with real customers, and then incorporate that feedback into the designs and what ultimately we end up launching.

Rinearson: One of the things I wanted to make sure of before I came to Twitter was to know that we would be able to build features in the open and solicit feedback and show rough drafts. And so this is something I asked Parag Agrawal, who’s now the CEO, and was the person who hired me. Pretty early in the job interview process, I said this was going to be really important, and he said, “If you think it’s important to the success of this work, great, do it—thumbs up.” He also shares that openness.

As you said, Tess, you come from crypto. When you were out there, what did you think Twitter was getting right? What did you think Twitter was getting wrong?

Rinearson: I had been a Twitter power user for a really long time. The thing that I saw was a lot of aesthetic alignment between how Twitter exists in the world and the way that crypto exists in the world. Twitter has decentralized user experiences in its DNA. And, this is a bit cheesy, but people use Twitter sometimes in ways that they use a public blockchain, as a public database where everything’s time stamped and people can agree on what happened.

And for most people it’s open, it is there for public conversation. And then obviously it was also the place—a place—where the crypto community really found its footing. I think it’s been a place where an enormous amount of discovery happens, and education and learning for the whole community. I joined when there were some murmurings about Twitter starting to do crypto stuff, mostly stuff Esther had led actually, and I was excited to see where it was going. And then Twitter’s investment in Bluesky also gave me a lot of confidence.

Let’s talk about the two main things you have delivered so far: The crypto tipping feature and NFT pictures. Can you give me just a potted history of how each came about and why?

Crawford: Those are our first set of early explorations, and the reason why we started there was we really wanted to make sure that what we built benefited creators, their audiences, and then all the conversations that are happening on Twitter. For creators in particular, we know that they rely on platforms like Twitter to monetize and earn a living, and not all people are able to use traditional currencies. Not everybody has a traditional banking account setup.

And so we wanted to provide an opportunity for a borderless payment solution, and that’s why we decided to go ahead and use Bitcoin Lightning as our first big integration. One of the reasons we chose Bitcoin Lightning was also because of the low transaction fees. And we have Bitcoin and Ethereum addresses that you can also put in there [on your Twitter “tipping jar”]. We noticed that people were actually adding information about their crypto wallet addresses in their profiles. And so we wanted to make a more seamless experience, so that people could just tip through the platform, so that it felt native.

With NFT profile pictures, the way that came about was, again, looking at user behavior. People were adding NFTs that they owned as avatars, but you didn’t really know whether they owned those NFTs or not. So we decided to go ahead and build out that feature so that one could actually prove ownership.

That’s similar to how other things developed on Twitter, right? The hashtag, or even even the retweet, were initially just things users invented—by adding the # sign, or by pasting other users’ tweets—and then Twitter made that a feature.

Crawford: Yeah, exactly. Many of the best ideas come from watching user behavior on the platform, and then we just productize that.

Rinearson: Sometimes I’ve heard people call that the “help wanted signs,” and like, keeping an eye out for the “help wanted signs” across the platform. The NFT profile picture was a clear example of that.

How do all these things—these two things and possibly other crypto features coming further down the line—really help Twitter’s bottom line?

Crawford: With creator monetization our goal was to help creators get paid, not Twitter. But Twitter takes a really small cut of earnings. For more successful creators, we take a larger percentage. The way we think about this is, it is part of our revenue diversification.

Twitter today is a wholly ad-based business. In the future we imagine Twitter making money from a variety of different product areas. So Twitter Blue is one of those products—you can pay $2.99 a month and you get additional features, such as the NFT profile pictures. We really think that revenue diversification sits across a variety of areas, and creator monetization is one really small component of that.

As you said, these are just early experiments. Where is Twitter Crypto going next? What’s your vision for crypto technology’s role within Twitter?

Rinearson: The real trick here is to find the right parts of Twitter to decentralize, and to not try to decentralize everything at once—or, you know, make every user suddenly responsible for taking care of some private keys or something like that.

We have to find the right ways to open up some access to a decentralized economic layer, or give people ways that they can take their identity with them, without relying on a single centralized service.

We’re really early in these explorations, and even looking at things like Bitcoin tipping or the NFT profile pictures—we view those features as experiments themselves in a lot of ways and learning experiences. We’re learning things about how our users relate to these concepts, what they understand about them, what they find confusing, and what’s most useful to them. We really want to try to use this technology to bring utility to people and you know, not just like, sprinkle a little blockchain on it for the sake of it. So creator monetization is an area that I’m really excited about because I think there’s a really clear path forward. But again, we’re looking beyond that: We’re also looking at using crypto technology in fields like [digital] identity and [digital] ownership space and also figuring out how we can better serve crypto communities on the platform.

Are you going to put Twitter verified users’ blue ticks on a blockchain, then?

[Laughter]

No?

[More laughter]

OK, moving on. How does the kind of work you do dovetail with Bluesky’s plan to create a protocol for a decentralized social media platform? Is there any synergy there?

Rinearson: I have known Jay [Graber], the Bluesky lead, for a long time, and she and I are in pretty close contact. We check in with each other regularly and talk a lot about problems we might have in common that we’ll both need to solve. There’s an overlap looking at things in the identity area, but at the end of the day, it’s a separate project. She’s pretty focused on hiring her team, and they’re very focused on building a prototype of a protocol. That is different from what Esther and I are thinking about, which is like: There are all these blockchain protocols that exist, and we need to figure out how to make them useful and accessible for real people.

And when I say “real people,” I mean that in a sort of tongue-in-cheek contrast to hardcore crypto nerds like me. Jay is thinking much more about building for people who are creating decentralized networks. That is a very different focus area. Beyond that, I would just say it’s too early to say what Bluesky will mean for Twitter as a product. We are in touch, we have aligned values. But at the end of the day—separate teams.

Why is a centralized Silicon Valley company like Twitter the right place to start to bring more decentralization to internet users? Don’t we have just to start from scratch, build a new platform that is already decentralized?

Rinearson: I started in crypto in 2015, and I have a very vivid memory from those years of watching some of my coworkers—crypto engineers—trying to figure out how to secure some of their Bitcoin like before one of the Bitcoin forks [in which the Bitcoin blockchain split, creating new currencies], and they were panicking and freaking out. I thought there was no way that a normal person would be able to handle this in a way that would be safe. And so I was a little bit disillusioned with crypto, especially from a consumer perspective.

And then last year, I started seeing more interest from people whom I’ve known for a long time and weren’t crypto people. They were just starting to perk their heads up and take notice and start creating NFTs or start talking about DAOs. And I thought that that was interesting, that we were coming around a corner, and it might be time to start thinking about what this could mean for people beyond that hardcore crypto group.

And that was when Twitter reached out. You know, I don’t think that just any centralized platform would be able to bring crypto to the masses, so to speak. But I think Twitter has the right stuff. I think you have to meet people where they are with new technologies: find ways to onboard them and bring them along and show them what this might mean for them. make things accessible. And it’s really, really hard to do that with just a protocol. You need to have some kind of community, you need to have some kind of user base, you need to have some kind of platform. And Twitter’s just right there.

I don’t think I would say that a centralized platform is definitely the way to “bring crypto to the masses.” I do think that Twitter is the way to do it.

But why do the masses need crypto right now?

Rinearson: I don’t know that anyone  needs crypto, and our goal is not to get everyone into crypto. Let’s be clear about that. But I do think that crypto is a potentially very powerful tool for people. And so I think what we are trying to do is show people how powerful it is and unlock those possibilities. It’s also possible that we create some products and features, where people actually don’t even really know what’s happening under the hood.

Like maybe we’re using crypto as a payment rail or again as an identity layer—users don’t necessarily need to know all of those implementation details. And that’s actually something we come back to a lot: What level of abstraction are we talking about with users? What story are we telling them about what’s happening under the hood? But yeah, I would just like to reiterate that the goal is not to just shovel everyone into crypto. We want to provide value for people.

Do you think there is a case for Twitter to launch its own cryptocurrency— a Twittercoin?

Rinearson: I think there’s a case for a lot of things—honestly, there’s a case for a lot of things. We’re trying to think really, really broadly about it.

Crawford: We’re actively exploring a lot of things. It’s not it’s not something we would be making an announcement about.

Rinearson: I think it is really important to stress that when you say “Twittercoin” you probably have a slightly different idea of what it is than we do. And are we exploring those ideas? Yes, we want to think about all of them. Do we have road maps for them? No. But are we trying to think about things really creatively and be really, really open-minded? Yes. We have this new economic technology that we think could unlock a lot of things for people. And we want to go down a bunch of rabbit holes and see what we come up with.

Gian M. Volpicelli is a senior writer at WIRED, where he covers cryptocurrency, decentralization, politics, and technology regulation. He received a master’s degree in journalism from City University of London after studying politics and international relations in Rome. He lives in London.

 

Highlighted Text in BLUE, BLACK, GREEN, RED by Aviva Lev-Ari, PhD, RN

SOURCE

https://www.wired.com/story/twitter-crypto-strategy/

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Data Science: Step by Step – A Resource for LPBI Group One-Year Internship in IT, IS, DS

Reporter: Aviva Lev-Ari, PhD, RN

9 free Harvard courses: learning Data Science

In this article, I will list 9 free Harvard courses that you can take to learn data science from scratch. Feel free to skip any of these courses if you already possess knowledge of that subject.

Step 1: Programming

The first step you should take when learning data science is to learn to code. You can choose to do this with your choice of programming language?—?ideally Python or R.

If you’d like to learn R, Harvard offers an introductory R course created specifically for data science learners, called Data Science: R Basics.

This program will take you through R concepts like variables, data types, vector arithmetic, and indexing. You will also learn to wrangle data with libraries like dplyr and create plots to visualize data.

If you prefer Python, you can choose to take CS50’s Introduction to Programming with Python offered for free by Harvard. In this course, you will learn concepts like functions, arguments, variables, data types, conditional statements, loops, objects, methods, and more.

Both programs above are self-paced. However, the Python course is more detailed than the R program, and requires a longer time commitment to complete. Also, the rest of the courses in this roadmap are taught in R, so it might be worth learning R to be able to follow along easily.

Step 2: Data Visualization

Visualization is one of the most powerful techniques with which you can translate your findings in data to another person.

With Harvard’s Data Visualization program, you will learn to build visualizations using the ggplot2 library in R, along with the principles of communicating data-driven insights.

Step 3: Probability

In this course, you will learn essential probability concepts that are fundamental to conducting statistical tests on data. The topics taught include random variables, independence, Monte Carlo simulations, expected values, standard errors, and the Central Limit Theorem.

The concepts above will be introduced with the help of a case study, which means that you will be able to apply everything you learned to an actual real-world dataset.

Step 4: Statistics

After learning probability, you can take this course to learn the fundamentals of statistical inference and modelling.
This program will teach you to define population estimates and margin of errors, introduce you to Bayesian statistics, and provide you with the fundamentals of predictive modeling.

Step 5: Productivity Tools (Optional)

I’ve included this project management course as optional since it isn’t directly related to learning data science. Rather, you will be taught to use Unix/Linux for file management, Github, version control, and creating reports in R.

The ability to do the above will save you a lot of time and help you better manage end-to-end data science projects.

Step 6: Data Pre-Processing

The next course in this list is called Data Wrangling, and will teach you to prepare data and convert it into a format that is easily digestible by machine learning models.

You will learn to import data into R, tidy data, process string data, parse HTML, work with date-time objects, and mine text.

As a data scientist, you often need to extract data that is publicly available on the Internet in the form of a PDF document, HTML webpage, or a Tweet. You will not always be presented with clean, formatted data in a CSV file or Excel sheet.

By the end of this course, you will learn to wrangle and clean data to come up with critical insights from it.

Step 7: Linear Regression

Linear regression is a machine learning technique that is used to model a linear relationship between two or more variables. It can also be used to identify and adjust the effect of confounding variables.

This course will teach you the theory behind linear regression models, how to examine the relationship between two variables, and how confounding variables can be detected and removed before building a machine learning algorithm.

Step 8: Machine Learning

Finally, the course you’ve probably been waiting for! Harvard’s machine learning program will teach you the basics of machine learning, techniques to mitigate overfitting, supervised and unsupervised modelling approaches, and recommendation systems.

Step 9: Capstone Project

After completing all the above courses, you can take Harvard’s data science capstone project, where your skills in data visualization, probability, statistics, data wrangling, data organization, regression, and machine learning will be assessed.

With this final project, you will get the opportunity to put together all the knowledge learnt from the above courses and gain the ability to complete a hands-on data science project from scratch.

Note: All the courses above are available on an online learning platform from edX and can be audited for free. If you want a course certificate, however, you will have to pay for one.

Building a data science learning roadmap with free courses offered by MIT.

8 Free MIT Courses to Learn Data Science Online

 enrolled into an undergraduate computer science program and decided to major in data science. I spent over $25K in tuition fees over the span of three years, only to graduate and realize that I wasn’t equipped with the skills necessary to land a job in the field.

I barely knew how to code, and was unclear about the most basic machine learning concepts.

I took some time out to try and learn data science myself — with the help of YouTube videos, online courses, and tutorials. I realized that all of this knowledge was publicly available on the Internet and could be accessed for free.

It came as a surprise that even Ivy League universities started making many of their courses accessible to students worldwide, for little to no charge. This meant that people like me could learn these skills from some of the best institutions in the world, instead of spending thousands of dollars on a subpar degree program.

In this article, I will provide you with a data science roadmap I created using only freely available MIT online courses.

Step 1: Learn to code

I highly recommend learning a programming language before going deep into the math and theory behind data science models. Once you learn to code, you will be able to work with real-world datasets and get a feel of how predictive algorithms function.

MIT Open Courseware offers a beginner-friendly Python program for beginners, called Introduction to Computer Science and Programming.

This course is designed to help people with no prior coding experience to write programs to tackle useful problems.

Step 2: Statistics

Statistics is at the core of every data science workflow — it is required when building a predictive model, analyzing trends in large amounts of data, or selecting useful features to feed into your model.

MIT Open Courseware offers a beginner-friendly course called Introduction to Probability and Statistics. After taking this course, you will learn the basic principles of statistical inference and probability. Some concepts covered include conditional probability, Bayes theorem, covariance, central limit theorem, resampling, and linear regression.

This course will also walk you through statistical analysis using the R programming language, which is useful as it adds on to your tool stack as a data scientist.

Another useful program offered by MIT for free is called Statistical Thinking and Data Analysis. This is another elementary course in the subject that will take you through different data analysis techniques in Excel, R, and Matlab.

You will learn about data collection, analysis, different types of sampling distributions, statistical inference, linear regression, multiple linear regression, and nonparametric statistical methods.

Step 3: Foundational Math Skills

Calculus and linear algebra are two other branches of math that are used in the field of machine learning. Taking a course or two in these subjects will give you a different perspective of how predictive models function, and the working behind the underlying algorithm.

To learn calculus, you can take Single Variable Calculus offered by MIT for free, followed by Multivariable Calculus.

Then, you can take this Linear Algebra class by Prof. Gilbert Strang to get a strong grasp of the subject.

All of the above courses are offered by MIT Open Courseware, and are paired with lecture notes, problem sets, exam questions, and solutions.

Step 4: Machine Learning

Finally, you can use the knowledge gained in the courses above to take MIT’s Introduction to Machine Learning course. This program will walk you through the implementation of predictive models in Python.

The core focus of this course is in supervised and reinforcement learning problems, and you will be taught concepts such as generalization and how overfitting can be mitigated. Apart from just working with structured datasets, you will also learn to process image and sequential data.

MIT’s machine learning program cites three pre-requisites — Python, linear algebra, and calculus, which is why it is advisable to take the courses above before starting this one.

Are These Courses Beginner-Friendly?

Even if you have no prior knowledge of programming, statistics, or mathematics, you can take all the courses listed above.

MIT has designed these programs to take you through the subject from scratch. However, unlike many MOOCs out there, the pace does build up pretty quickly and the courses cover a large depth of information.

Due to this, it is advisable to do all the exercises that come with the lectures and work through all the reading material provided.

SOURCE

Natassha Selvaraj is a self-taught data scientist with a passion for writing. You can connect with her on LinkedIn.

https://www.kdnuggets.com/2022/03/8-free-mit-courses-learn-data-science-online.html

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From the journal Nature: NFT, Patents, and Intellectual Property: Potential Design

Reporter: Stephen J. Williams, Ph.D.

 

From the journal Nature

Source: https://www.nature.com/articles/s41598-022-05920-6

Patents and intellectual property assets as non-fungible tokens; key technologies and challenges

Scientific Reports volume 12, Article number: 2178 (2022)

Abstract

With the explosive development of decentralized finance, we witness a phenomenal growth in tokenization of all kinds of assets, including equity, funds, debt, and real estate. By taking advantage of blockchain technology, digital assets are broadly grouped into fungible and non-fungible tokens (NFT). Here non-fungible tokens refer to those with unique and non-substitutable properties. NFT has widely attracted attention, and its protocols, standards, and applications are developing exponentially. It has been successfully applied to digital fantasy artwork, games, collectibles, etc. However, there is a lack of research in utilizing NFT in issues such as Intellectual Property. Applying for a patent and trademark is not only a time-consuming and lengthy process but also costly. NFT has considerable potential in the intellectual property domain. It can promote transparency and liquidity and open the market to innovators who aim to commercialize their inventions efficiently. The main objective of this paper is to examine the requirements of presenting intellectual property assets, specifically patents, as NFTs. Hence, we offer a layered conceptual NFT-based patent framework. Furthermore, a series of open challenges about NFT-based patents and the possible future directions are highlighted. The proposed framework provides fundamental elements and guidance for businesses in taking advantage of NFTs in real-world problems such as grant patents, funding, biotechnology, and so forth.

Introduction

Distributed ledger technologies (DLTs) such as blockchain are emerging technologies posing a threat to existing business models. Traditionally, most companies used centralized authorities in various aspects of their business, such as financial operations and setting up a trust with their counterparts. By the emergence of blockchain, centralized organizations can be substituted with a decentralized group of resources and actors. The blockchain mechanism was introduced in Bitcoin white paper in 2008, which lets users generate transactions and spend their money without the intervention of banks1. Ethereum, which is a second generation of blockchain, was introduced in 2014, allowing developers to run smart contracts on a distributed ledger. With smart contracts, developers and businesses can create financial applications that use cryptocurrencies and other forms of tokens for applications such as decentralized finance (DeFi), crowdfunding, decentralized exchanges, data records keeping, etc.2. Recent advances in distributed ledger technology have developed concepts that lead to cost reduction and the simplification of value exchange. Nowadays, by leveraging the advantages of blockchain and taking into account the governance issues, digital assets could be represented as tokens that existed in the blockchain network, which facilitates their transmission and traceability, increases their transparency, and improves their security3.

In the landscape of blockchain technology, there could be defined two types of tokens, including fungible tokens, in which all the tokens have equal value and non-fungible tokens (NFTs) that feature unique characteristics and are not interchangeable. Actually, non-fungible tokens are digital assets with a unique identifier that is stored on a blockchain4. NFT was initially suggested in Ethereum Improvement Proposals (EIP)-7215, and it was later expanded in EIP-11556. NFTs became one of the most widespread applications of blockchain technology that reached worldwide attention in early 2021. They can be digital representations of real-world objects. NFTs are tradable rights of digital assets (pictures, music, films, and virtual creations) where ownership is recorded in blockchain smart contracts7.

In particular, fungibility is the ability to exchange one with another of the same kind as an essential currency feature. The non-fungible token is unique and therefore cannot be substituted8. Recently, blockchain enthusiasts have indicated significant interest in various types of NFTs. They enthusiastically participate in NFT-related games or trades. CryptoPunks9, as one of the first NFTs on Ethereum, has developed almost 10,000 collectible punks and helped popularize the ERC-721 Standard. With the gamification of the breeding mechanics, CryptoKitties10 officially placed NFTs at the forefront of the market in 2017. CryptoKitties is an early blockchain game that enables users to buy, sell, collect, and digital breed cats. Another example is NBA Top Shot11, an NFT trading platform for digital short films buying and selling NBA events.

NFTs are developing remarkably and have provided many applications such as artist royalties, in-game assets, educational certificates, etc. However, it is a relatively new concept, and many areas of application need to be explored. Intellectual Property, including patent, trademark, and copyright, is an important area where NFTs can be applied usefully and solve existing problems.

Although NFTs have had many applications so far, it rarely has been used to solve real-world problems. In fact, an NFT is an exciting concept about Intellectual Property (IP). Applying for a patent and trademark is a time-consuming and lengthy process, but it is also costly. That is, registering a copyright or trademark may take months, while securing a patent can take years. On the contrary, with the help of unique features of NFT technology, it is possible to accelerate this process with considerable confidence and assurance about protecting the ownership of an IP. NFTs can offer IP protection while an applicant waits for the government to grant his/her more formal protection. It is cause for excitement that people who believe NFTs and Blockchain would make buying and selling patents easier, offering new opportunities for companies, universities, and inventors to make money off their innovations12. Patent holders will benefit from such innovation. It would give them the ability to ‘tokenize’ their patents. Because every transaction would be logged on a blockchain, it will be much easier to trace patent ownership changes. However, NFT would also facilitate the revenue generation of patents by democratizing patent licensing via NFT. NFTs support the intellectual property market by embedding automatic royalty collecting methods inside inventors’ works, providing them with financial benefits anytime their innovation is licensed. For example, each inventor’s patent would be minted as an NFT, and these NFTs would be joined together to form a commercial IP portfolio and minted as a compounded NFT. Each investor would automatically get their fair share of royalties whenever the licensing revenue is generated without tracking them down.

The authors in13, an overview of NFTs’ applications in different aspects such as gambling, games, and collectibles has been discussed. In addition4, provides a prototype for an event-tracking application based on Ethereum smart contract, and NFT as a solution for art and real estate auction systems is described in14. However, these studies have not discussed existing standards or a generalized architecture, enabling NFTs to be applied in diverse applications. For example, the authors in15 provide two general design patterns for creating and trading NFTs and discuss existing token standards for NFT. However, the proposed designs are limited to Ethereum, and other blockchains are not considered16. Moreover, different technologies for each step of the proposed procedure are not discussed. In8, the authors provide a conceptual framework for token designing and managing and discuss five views: token view, wallet view, transaction view, user interface view, and protocol view. However, no research provides a generalized conceptual framework for generating, recording, and tracing NFT based-IP, in blockchain network.

Even with the clear benefits that NFT-backed patents offer, there are a number of impediments to actually achieving such a system. For example, convincing patent owners to put current ownership records for their patents into NFTs poses an initial obstacle. Because there is no reliable framework for NFT-based patents, this paper provides a conceptual framework for presenting NFT-based patents with a comprehensive discussion on many aspects, ranging from the background, model components, token standards to application domains and research challenges. The main objective of this paper is to provide a layered conceptual NFT-based patent framework that can be used to register patents in a decentralized, tamper-proof, and trustworthy peer-to-peer network to trade and exchange them in the worldwide market. The main contributions of this paper are highlighted as follows:

  • Providing a comprehensive overview on tokenization of IP assets to create unique digital tokens.
  • Discussing the components of a distributed and trustworthy framework for minting NFT-based patents.
  • Highlighting a series of open challenges of NFT-based patents and enlightening the possible future trends.

The rest of the paper is structured as follows: “Background” section describes the Background of NFTs, Non-Fungible Token Standards. The NFT-based patent framework is described in “NFT-based patent framework” section. The Discussion and challenges are presented in “Discussion” section. Lastly, conclusions are given in “Conclusion” section.

Background

Colored Coins could be considered the first steps toward NFTs designed on the top of the Bitcoin network. Bitcoins are fungible, but it is possible to mark them to be distinguishable from the other bitcoins. These marked coins have special properties representing real-world assets like cars and stocks, and owners can prove their ownership of physical assets through the colored coins. By utilizing Colored Coins, users can transfer their marked coins’ ownership like a usual transaction and benefit from Bitcoin’s decentralized network17. Colored Coins had limited functionality due to the Bitcoin script limitations. Pepe is a green frog meme originated by Matt Furie that; users define tokens for Pepes and trade them through the Counterparty platform. Then, the tokens that were created by the picture of Pepes are decided if they are rare enough. Rare Pepe allows users to preserve scarcity, manage the ownership, and transfer their purchased Pepes.

In 2017, Larva Labs developed the first Ethereum-based NFT named CryptoPunks. It contains 10,000 unique human-like characters generated randomly. The official ownership of each character is stored in the Ethereum smart contract, and owners would trade characters. CryptoPunks project inspired CryptoKitties project. CryptoKitties attracts attention to NFT, and it is a pioneer in blockchain games and NFTs that launched in late 2017. CryptoKitties is a blockchain-based virtual game, and users collect and trade characters with unique features that shape kitties. This game was developed in Ethereum smart contract, and it pioneered the ERC-721 token, which was the first standard token in the Ethereum blockchain for NFTs. After the 2017 hype in NFTs, many projects started in this context. Due to increased attention to NFTs’ use-cases and growing market cap, different blockchains like EOS, Algorand, and Tezos started to support NFTs, and various marketplaces like SuperRare and Rarible, and OpenSea are developed to help users to trade NFTs. As mentioned, in general, assets are categorized into two main classes, fungible and non-fungible assets. Fungible assets are the ones that another similar asset can replace. Fungible items could have two main characteristics: replicability and divisibility.

Currency is a fungible item because a ten-dollar bill can be exchanged for another ten-dollar bill or divided into ten one-dollar bills. Despite fungible items, non-fungible items are unique and distinguishable. They cannot be divided or exchanged by another identical item. The first tweet on Twitter is a non-fungible item with mentioned characteristics. Another tweet cannot replace it, and it is unique and not divisible. NFT is a non-fungible cryptographic asset that is declared in a standard token format and has a unique set of attributes. Due to transparency, proof of ownership, and traceable transactions in the blockchain network, NFTs are created using blockchain technology.

Blockchain-based NFTs help enthusiasts create NFTs in the standard token format in blockchain, transfer the ownership of their NFTs to a buyer, assure uniqueness of NFTs, and manage NFTs completely. In addition, there are semi-fungible tokens that have characteristics of both fungible and non-fungible tokens. Semi-fungible tokens are fungible in the same class or specific time and non-fungible in other classes or different times. A plane ticket can be considered a semi-fungible token because a charter ticket can be exchanged by another charter ticket but cannot be exchanged by a first-class ticket. The concept of semi-fungible tokens plays the main role in blockchain-based games and reduces NFTs overhead. In Fig. 1, we illustrate fungible, non-fungible, and semi-fungible tokens. The main properties of NFTs are described as follows15:

figure 1
Figure 1

Ownership: Because of the blockchain layer, the owner of NFT can easily prove the right of possession by his/her keys. Other nodes can verify the user’s ownership publicly.

  • Transferable: Users can freely transfer owned NFTs ownership to others on dedicated markets.
  • Transparency: By using blockchain, all transactions are transparent, and every node in the network can confirm and trace the trades.
  • Fraud Prevention: Fraud is one of the key problems in trading assets; hence, using NFTs ensures buyers buy a non-counterfeit item.
  • Immutability: Metadata, token ID, and history of transactions of NFTs are recorded in a distributed ledger, and it is impossible to change the information of the purchased NFTs.

Non-fungible standards

Ethereum blockchain was pioneered in implementing NFTs. ERC-721 token was the first standard token accepted in the Ethereum network. With the increase in popularity of the NFTs, developers started developing and enhancing NFTs standards in different blockchains like EOS, Algorand, and Tezos. This section provides a review of implemented NFTs standards on the mentioned blockchains.

Ethereum

ERC-721 was the first Standard for NFTs developed in Ethereum, a free and open-source standard. ERC-721 is an interface that a smart contract should implement to have the ability to transfer and manage NFTs. Each ERC-721 token has unique properties and a different Token Id. ERC-721 tokens include the owner’s information, a list of approved addresses, a transfer function that implements transferring tokens from owner to buyer, and other useful functions5.

In ERC-721, smart contracts can group tokens with the same configuration, and each token has different properties, so ERC-721 does not support fungible tokens. However, ERC-1155 is another standard on Ethereum developed by Enjin and has richer functionalities than ERC-721 that supports fungible, non-fungible, and semi-fungible tokens. In ERC-1155, IDs define the class of assets. So different IDs have a different class of assets, and each ID may contain different assets of the same class. Using ERC-1155, a user can transfer different types of tokens in a single transaction and mix multiple fungible and non-fungible types of tokens in a single smart contract6. ERC-721 and ERC-1155 both support operators in which the owner can let the operator originate transferring of the token.

EOSIO

EOSIO is an open-source blockchain platform released in 2018 and claims to eliminate transaction fees and increase transaction throughput. EOSIO differs from Ethereum in the wallet creation algorithm and procedure of handling transactions. dGood is a free standard developed in the EOS blockchain for assets, and it focuses on large-scale use cases. It supports a hierarchical naming structure in smart contracts. Each contract has a unique symbol and a list of categories, and each category contains a list of token names. Therefore, a single contract in dGoods could contain many tokens, which causes efficiency in transferring a group of tokens. Using this hierarchy, dGoods supports fungible, non-fungible, and semi-fungible tokens. It also supports batch transferring, where the owner can transfer many tokens in one operation18.

Algorand

Algorand is a new high-performance public blockchain launched in 2019. It provides scalability while maintaining security and decentralization. It supports smart contracts and tokens for representing assets19. Algorand defines Algorand Standard Assets (ASA) concept to create and manage assets in the Algorand blockchain. Using ASA, users are able to define fungible and non-fungible tokens. In Algorand, users can create NFTs or FTs without writing smart contracts, and they should run just a single transaction in the Algorand blockchain. Each transaction contains some mutable and immutable properties20.

Each account in Algorand can create up to 1000 assets, and for every asset, an account creates or receives, the minimum balance of the account increases by 0.1 Algos. Also, Algorand supports fractional NFTs by splitting an NFT into a group of divided FTs or NFTs, and each part can be exchanged dependently21. Algorand uses a Clawback Address that operates like an operator in ERC-1155, and it is allowed to transfer tokens of an owner who has permitted the operator.

Tezos

Tezos is another decentralized open-source blockchain. Tezos supports the meta-consensus concept. In addition to using a consensus protocol on the ledger’s state like Bitcoin and Ethereum, It also attempts to reach a consensus about how nodes and the protocol should change or upgrade22. FA2 (TZIP-12) is a standard for a unified token contract interface in the Tezos blockchain. FA2 supports different token types like fungible, non-fungible, and fractionalized NFT contracts. In Tezos, tokens are identified with a token contract address and token ID pair. Also, Tezos supports batch token transferring, which reduces the cost of transferring multiple tokens.

Flow

Flow was developed by Dapper Labs to remove the scalability limitation of the Ethereum blockchain. Flow is a fast and decentralized blockchain that focuses on games and digital collectibles. It improves throughput and scalability without sharding due to its architecture. Flow supports smart contracts using Cadence, which is a resource-oriented programming language. NFTs can be described as a resource with a unique id in Cadence. Resources have important rules for ownership management; that is, resources have just one owner and cannot be copied or lost. These features assure the NFT owner. NFTs’ metadata, including images and documents, can be stored off-chain or on-chain in Flow. In addition, Flow defines a Collection concept, in which each collection is an NFT resource that can include a list of resources. It is a dictionary that the key is resource id, and the value is corresponding NFT.

The collection concept provides batch transferring of NFTs. Besides, users can define an NFT for an FT. For instance, in CryptoKitties, a unique cat as an NFT can own a unique hat (another NFT). Flow uses Cadence’s second layer of access control to allow some operators to access some fields of the NFT23. In Table 1, we provide a comparison between explained standards. They are compared in support of fungible-tokens, non-fungible tokens, batch transferring that owner can transform multiple tokens in one operation, operator support in which the owner can approve an operator to originate token transfer, and fractionalized NFTs that an NFT can divide to different tokens and each exchange dependently.Table 1 Comparing NFT standards.

Full size table

NFT-based patent framework

In this section, we propose a framework for presenting NFT-based patents. We describe details of the proposed distributed and trustworthy framework for minting NFT-based patents, as shown in Fig. 2. The proposed framework includes five main layers: Storage Layer, Authentication Layer, Verification Layer, Blockchain Layer, and Application Layer. Details of each layer and the general concepts are presented as follows.

figure 2
Figure 2

Storage layer

The continuous rise of the data in blockchain technology is moving various information systems towards the use of decentralized storage networks. Decentralized storage networks were created to provide more benefits to the technological world24. Some of the benefits of using decentralized storage systems are explained: (1) Cost savings are achieved by making optimal use of current storage. (2) Multiple copies are kept on various nodes, avoiding bottlenecks on central servers and speeding up downloads. This foundation layer implicitly provides the infrastructure required for the storage. The items on NFT platforms have unique characteristics that must be included for identification.

Non-fungible token metadata provides information that describes a particular token ID. NFT metadata is either represented on the On-chain or Off-chain. On-chain means direct incorporation of the metadata into the NFT’s smart contract, which represents the tokens. On the other hand, off-chain storage means hosting the metadata separately25.

Blockchains provide decentralization but are expensive for data storage and never allow data to be removed. For example, because of the Ethereum blockchain’s current storage limits and high maintenance costs, many projects’ metadata is maintained off-chain. Developers utilize the ERC721 Standard, which features a method known as tokenURI. This method is implemented to let applications know the location of the metadata for a specific item. Currently, there are three solutions for off-chain storage, including InterPlanetary File System (IPFS), Pinata, and Filecoin.

IPFS

InterPlanetary File System (IPFS) is a peer-to-peer hypermedia protocol for decentralized media content storage. Because of the high cost of storing media files related to NFTS on Blockchain, IPFS can be the most affordable and efficient solution. IPFS combines multiple technologies inspired by Gita and BitTorrent, such as Block Exchange System, Distributed Hash Tables (DHT), and Version Control System26. On a peer-to-peer network, DHT is used to coordinate and maintain metadata.

In other words, the hash values must be mapped to the objects they represent. An IPFS generates a hash value that starts with the prefix {Q}_{m} and acts as a reference to a specific item when storing an object like a file. Objects larger than 256 KB are divided into smaller blocks up to 256 KB. Then a hash tree is used to interconnect all the blocks that are a part of the same object. IPFS uses Kamdelia DHT. The Block Exchange System, or BitSwap, is a BitTorrent-inspired system that is used to exchange blocks. It is possible to use asymmetric encryption to prevent unauthorized access to stored content on IPFS27.

Pinata

Pinata is a popular platform for managing and uploading files on IPFS. It provides secure and verifiable files for NFTs. Most data is stored off-chain by most NFTs, where a URL of the data is pointed to the NFT on the blockchain. The main problem here is that some information in the URL can change.

This indicates that an NFT supposed to describe a certain patent can be changed without anyone knowing. This defeats the purpose of the NFT in the first place. This is where Pinata comes in handy. Pinata uses the IPFS to create content-addressable hashes of data, also known as Content-Identifiers (CIDs). These CIDs serve as both a way of retrieving data and a means to ensure data validity. Those looking to retrieve data simply ask the IPFS network for the data associated with a certain CID, and if any node on the network contains that data, it will be returned to the requester. The data is automatically rehashed on the requester’s computer when the requester retrieves it to make sure that the data matches back up with the original CID they asked for. This process ensures the data that’s received is exactly what was asked for; if a malicious node attempts to send fake data, the resulting CID on the requester’s end will be different, alerting the requester that they’re receiving incorrect data28.

Filecoin

Another decentralized storage network is Filecoin. It is built on top of IPFS and is designed to store the most important data, such as media files. Truffle Suite has also launched NFT Development Template with Filecoin Box. NFT.Storage (Free Decentralized Storage for NFTs)29 allows users to easily and securely store their NFT content and metadata using IPFS and Filecoin. NFT.Storage is a service backed by Protocol Labs and Pinata specifically for storing NFT data. Through content addressing and decentralized storage, NFT.Storage allows developers to protect their NFT assets and associated metadata, ensuring that all NFTs follow best practices to stay accessible for the long term. NFT.Storage makes it completely frictionless to mint NFTs following best practices through resilient persistence on IPFS and Filecoin. NFT.Storage allows developers to quickly, safely, and for free store NFT data on decentralized networks. Anyone can leverage the power of IPFS and Filecoin to ensure the persistence of their NFTs. The details of this system are stated as follows30:

Content addressing

Once users upload data on NFT.Storage, They receive a CID, which is an IPFS hash of the content. CIDs are the data’s unique fingerprints, universal addresses that can be used to refer to it regardless of how or where it is stored. Using CIDs to reference NFT data avoids problems such as weak links and “rug pulls” since CIDs are generated from the content itself.

Provable storage

NFT.Storage uses Filecoin for long-term decentralized data storage. Filecoin uses cryptographic proofs to assure the NFT data’s durability and persistence over time.

Resilient retrieval

This data stored via IPFS and Filecoin can be fetched directly in the browser via any public IPFS.

Authentication Layer

The second layer is the authentication layer, which we briefly highlight its functions in this section. The Decentralized Identity (DID) approach assists users in collecting credentials from a variety of issuers, such as the government, educational institutions, or employers, and saving them in a digital wallet. The verifier then uses these credentials to verify a person’s validity by using a blockchain-based ledger to follow the “identity and access management (IAM)” process. Therefore, DID allows users to be in control of their identity. A lack of NFT verifiability also causes intellectual property and copyright infringements; of course, the chain of custody may be traced back to the creator’s public address to check whether a similar patent is filed using that address. However, there is no quick and foolproof way to check an NFTs creator’s legitimacy. Without such verification built into the NFT, an NFT proves ownership only over that NFT itself and nothing more.

Self-sovereign identity (SSI)31 is a solution to this problem. SSI is a new series of standards that will guide a new identity architecture for the Internet. With a focus on privacy, security interoperability, SSI applications use public-key cryptography with public blockchains to generate persistent identities for people with private and selective information disclosure. Blockchain technology offers a solution to establish trust and transparency and provide a secure and publicly verifiable KYC (Know Your Customer). The blockchain architecture allows you to collect information from various service providers into a single cryptographically secure and unchanging database that does not need a third party to verify the authenticity of the information.

The proposed platform generates patents-related smart contracts acting as a program that runs on the blockchain to receive and send transactions. They are unalterable privately identifying clients with a thorough KYC process. After KYC approval, then mint an NFT on the blockchain as a certificate of verification32. This article uses a decentralized authentication solution at this layer for authentication. This solution has been used for various applications in the field of the blockchain (exp: smart city, Internet of Things, etc.3334, but we use it here for the proposed framework (patent as NFTs). Details of this solution will be presented in the following.

Decentralized authentication

This section presents the authentication layer similar35 to build validated communication in a secure and decentralized manner via blockchain technology. As shown in Fig. 3, the authentication protocol comprises two processes, including registration and login.

figure 3
Figure 3
Registration

In the registration process of a suggested authentication protocol, we first initialize a user’s public key as their identity key (UserName). Then, we upload this identity key on a blockchain, in which transactions can be verified later by other users. Finally, the user generates an identity transaction.

Login

After registration, a user logs in to the system. The login process is described as follows:

  • 1. The user commits identity information and imports their secret key into the service application to log in.
  • 2. A user who needs to log in sends a login request to the network’s service provider.
  • 3. The service provider analyzes the login request, extracts the hash, queries the blockchain, and obtains identity information from an identity list (identity transactions).
  • 4. The service provider responds with an authentication request when the above process is completed. A timestamp (to avoid a replay attack), the user’s UserName, and a signature are all included in the authentication request.
  • 5. The user creates a signature with five parameters: timestamp, UserName, and PK, as well as the UserName and PK of the service provider. The user authentication credential is used as the signature.
  • 6. The service provider verifies the received information, and if the received information is valid, the authentication succeeds; otherwise, the authentication fails, and the user’s login is denied.

The World Intellectual Property Organization (WIPO) and multiple target patent offices in various nations or regions should assess a patent application, resulting in inefficiency, high costs, and uncertainty. This study presented a conceptual NFT-based patent framework for issuing, validating, and sharing patent certificates. The platform aims to support counterfeit protection as well as secure access and management of certificates according to the needs of learners, companies, education institutions, and certification authorities.

Here, the certification authority (CA) is used to authenticate patent offices. The procedure will first validate a patent if it is provided with a digital certificate that meets the X.509 standard. Certificate authorities are introduced into the system to authenticate both the nodes and clients connected to the blockchain network.

Verification layer

In permissioned blockchains, just identified nodes can read and write in the distributed ledger. Nodes can act in different roles and have various permissions. Therefore, a distributed system can be designed to be the identified nodes for patent granting offices. Here the system is described conceptually at a high level. Figure 4 illustrates the sequence diagram of this layer. This layer includes four levels as below:

figure 4
Figure 4

Digitalization

For a patent to publish as an NFT in the blockchain, it must have a digitalized format. This level is the “filling step” in traditional patent registering. An application could be designed in the application layer to allow users to enter different patent information online.

Recording

Patents provide valuable information and would bring financial benefits for their owner. If they are publicly published in a blockchain network, miners may refuse the patent and take the innovation for themselves. At least it can weaken consensus reliability and encourage miners to misbehave. The inventor should record his innovation privately first using proof of existence to prevent this. The inventor generates the hash of the patent document and records it in the blockchain. As soon as it is recorded in the blockchain, the timestamp and the hash are available for others publicly. Then, the inventor can prove the existence of the patent document whenever it is needed.

Furthermore, using methods like Decision Thinking36, an inventor can record each phase of patent development separately. In each stage, a user generates the hash of the finished part and publishes the hash regarding the last part’s hash. Finally, they have a coupled series of hashes that indicate patent development, and they can prove the existence of each phase using the original related documents. This level should be done to prevent others from abusing the patent and taking it for themselves. The inventor can make sure that their patent document is recorded confidentially and immutably37.

Different hash algorithms exist with different architecture, time complexity, and security considerations. Hash functions should satisfy two main requirements: Pre-Image Resistance: This means that it should be computationally hard to find the input of a hash function while the output and the hash algorithm are known publicly. Collision Resistance: This means that it is computationally hard to find two arbitrary inputs, x, and y, that have the same hash output. These requirements are vital for recording patents. First, the hash function should be Pre-Image Resistance to make it impossible for others to calculate the patent documentation. Otherwise, everybody can read the patent, even before its official publication. Second, the hash function should satisfy Collision Resistance to preclude users from changing their document after recording. Otherwise, users can upload another document, and after a while, they can replace it with another one.

There are various hash algorithms, and MD and SHA families are the most useful algorithms. According to38, Collisions have been found for MD2, MD4, MD5, SHA-0, and SHA-1 hash functions. Hence, they cannot be a good choice for recording patents. SHA2 hash algorithm is secure, and no collision has been found. Although SHA2 is noticeably slower than prior hash algorithms, the recording phase is not highly time-sensitive. So, it is a better choice and provides excellent security for users.

Validating

In this phase, the inventors first create NFT for their patents and publish it to the miners/validators. Miners are some identified nodes that validate NFTs to record in the blockchain. Due to the specialization of the patent validation, miners cannot be inexpert public persons. In addition, patent offices are not too many to make the network fully decentralized. Therefore, the miners can be related specialist persons that are certified by the patent offices. They should receive a digital certificate from patent offices that show their eligibility to referee a patent.

Digital certificate

Digital certificates are digital credentials used to verify networked entities’ online identities. They usually include a public key as well as the owner’s identification. They are issued by Certification Authorities (CAs), who must verify the certificate holder’s identity. Certificates contain cryptographic keys for signing, encryption, and decryption. X.509 is a standard that defines the format of public-key certificates and is signed by a certificate authority. X.509 standard has multiple fields, and its structure is shown in Fig. 5. Version: This field indicated the version of the X.509 standard. X.509 contains multiple versions, and each version has a different structure. According to the CA, validators can choose their desired version. Serial Number: It is used to distinguish a certificate from other certificates. Thus, each certificate has a unique serial number. Signature Algorithm Identifier: This field indicates the cryptographic encryption algorithm used by a certificate authority. Issuer Name: This field indicates the issuer’s name, which is generally certificate authority. Validity Period: Each certificate is valid for a defined period, defined as the Validity Period. This limited period partly protects certificates against exposing CA’s private key. Subject Name: Name of the requester. In our proposed framework, it is the validator’s name. Subject Public Key Info: Shows the CA’s or organization’s public key that issued the certificate. These fields are identical among all versions of the X.509 standard39.

figure 5
Figure 5

Certificate authority

A Certificate Authority (CA) issues digital certificates. CAs encrypt the certificate with their private key, which is not public, and others can decrypt the certificates containing the CA’s public key.

Here, the patent office creates a certificate for requested patent referees. The patent office writes the information of the validator in their certificate and encrypts it with the patent offices’ private key. The validator can use the certificate to assure others about their eligibility. Other nodes can check the requesting node’s information by decrypting the certificate using the public key of the patent office. Therefore, persons can join the network’s miners/validators using their credentials. In this phase, miners perform Formal Examinations, Prior Art Research, and Substantive Examinations and vote to grant or refuse the patent.

Miners perform a consensus about the patent and record the patent in the blockchain. After that, the NFT is recorded in the blockchain with corresponding comments in granting or needing reformations. If the miners detect the NFT as a malicious request, they do not record it in the blockchain.

Blockchain layer

This layer plays as a middleware between the Verification Layer and Application Layer in the patents as NFTs architecture. The main purpose of the blockchain layer in the proposed architecture is to provide IP management. We find that transitioning to a blockchain-based patent as a NFTs records system enables many previously suggested improvements to current patent systems in a flexible, scalable, and transparent manner.

On the other hand, we can use multiple blockchain platforms, including Ethereum, EOS, Flow, and Tezos. Blockchain Systems can be mainly classified into two major types: Permissionless (public) and Permissioned (private) Blockchains based on their consensus mechanism. In a public blockchain, any node can participate in the peer-to-peer network, where the blockchain is fully decentralized. A node can leave the network without any consent from the other nodes in the network.

Bitcoin is one of the most popular examples that fall under the public and permissionless blockchain. Proof of Work (POW), Proof-of-Stake (POS), and directed acyclic graph (DAG) are some examples of consensus algorithms in permissionless blockchains. Bitcoin and Ethereum, two famous and trustable blockchain networks, use the PoW consensus mechanism. Blockchain platforms like Cardano and EOS adopt the PoS consensus40.

Nodes require specific access or permission to get network authentication in a private blockchain. Hyperledger is among the most popular private blockchains, which allow only permissioned members to join the network after authentication. This provides security to a group of entities that do not completely trust one another but wants to achieve a common objective such as exchanging information. All entities of a permissioned blockchain network can use Byzantine-fault-tolerant (BFT) consensus. The Fabric has a membership identity service that manages user IDs and verifies network participants.

Therefore, members are aware of each other’s identity while maintaining privacy and secrecy because they are unaware of each other’s activities41. Due to their more secure nature, private blockchains have sparked a large interest in banking and financial organizations, believing that these platforms can disrupt current centralized systems. Hyperledger, Quorum, Corda, EOS are some examples of permissioned blockchains42.

Reaching consensus in a distributed environment is a challenge. Blockchain is a decentralized network with no central node to observe and check all transactions. Thus, there is a need to design protocols that indicate all transactions are valid. So, the consensus algorithms are considered as the core of each blockchain43. In distributed systems, the consensus has become a problem in which all network members (nodes) agree on accept or reject of a block. When all network members accept the new block, it can append to the previous block.

As mentioned, the main concern in the blockchains is how to reach consensus among network members. A wide range of consensus algorithms has been designed in which each of them has its own pros and cons42. Blockchain consensus algorithms are mainly classified into three groups shown in Table 2. As the first group, proof-based consensus algorithms require the nodes joining the verifying network to demonstrate their qualification to do the appending task. The second group is voting-based consensus that requires validators in the network to share their results of validating a new block or transaction before making the final decision. The third group is DAG-based consensus, a new class of consensus algorithms. These algorithms allow several different blocks to be published and recorded simultaneously on the network.Table 2 Consensus algorithms in blockchain networks.

Full size table

The proposed patent as the NFTs platform that builds blockchain intellectual property empowers the entire patent ecosystem. It is a solution that removes barriers by addressing fundamental issues within the traditional patent ecosystem. Blockchain can efficiently handle patents and trademarks by effectively reducing approval wait time and other required resources. The user entities involved in Intellectual Property management are Creators, Patent Consumers, and Copyright Managing Entities. Users with ownership of the original data are the patent creators, e.g., inventors, writers, and researchers. Patent Consumers are the users who are willing to consume the content and support the creator’s work. On the other hand, Users responsible for protecting the creators’ Intellectual Property are the copyright management entities, e.g., lawyers. The patents as NFTs solution for IP management in blockchain layer works by implementing the following steps62:

Creators sign up to the platform

Creators need to sign up on the blockchain platform to patent their creative work. The identity information will be required while signing up.

Creators upload IP on the blockchain network

Now, add an intellectual property for which the patent application is required. The creator will upload the information related to IP and the data on the blockchain network. Blockchain ensures traceability and auditability to prevent data from duplicity and manipulation. The patent becomes visible to all network members once it is uploaded to the blockchain.

Consumers generate request to use the content

Consumers who want to access the content must first register on the blockchain network. After Signing up, consumers can ask creators to grant access to the patented content. Before the patent owner authorizes the request, a Smart Contract is created to allow customers to access information such as the owner’s data. Furthermore, consumers are required to pay fees in either fiat money or unique tokens in order to use the creator’s original information. When the creator approves the request, an NDA (Non-Disclosure Agreement) is produced and signed by both parties. Blockchain manages the agreement and guarantees that all parties agree to the terms and conditions filed.

Patent management entities leverage blockchain to protect copyrights and solve related disputes

Blockchain assists the patent management entities in resolving a variety of disputes that may include: sharing confidential information, establishing proof of authorship, transferring IP rights, and making defensive publications, etc. Suppose a person used an Invention from a patent for his company without the inventor’s consent. The inventor can report it to the patent office and claim that he is the owner of that invention.

Application layer

The patent Platform Global Marketplace technology would allow many enterprises, governments, universities, and Small and medium-sized enterprises (SMEs) worldwide to tokenize patents as NFTs to create an infrastructure for storing patent records on a blockchain-based network and developing a decentralized marketplace in which patent holders would easily sell or otherwise monetize their patents. The NFTs-based patent can use smart contracts to determine a set price for a license or purchase.

Any buyer satisfied with the conditions can pay and immediately unlock the rights to the patent without either party ever having to interact directly. While patents are currently regulated jurisdictionally around the world, a blockchain-based patent marketplace using NFTs can reduce the geographical barriers between patent systems using as simple a tool as a search query. The ease of access to patents globally can help aspiring inventors accelerate the innovative process by building upon others’ patented inventions through licenses. There are a wide variety of use cases for patent NFTs such as SMEs, Patent Organization, Grant & Funding, and fundraising/transferring information relating to patents. These applications keep growing as time progresses, and we are constantly finding new ways to utilize these tokens. Some of the most commonly used applications can be seen as follows.

SMEs

The aim is to move intellectual property assets onto a digital, centralized, and secure blockchain network, enabling easier commercialization of patents, especially for small or medium enterprises (SMEs). Smart contracts can be attached to NFTs so terms of use and ownership can be outlined and agreed upon without incurring as many legal fees as traditional IP transfers. This is believed to help SMEs secure funding, as they could more easily leverage the previously undisclosed value of their patent portfolios63.

Transfer ownership of patents

NFTs can be used to transfer ownership of patents. The blockchain can be used to keep track of patent owners, and tokens would include self-executing contracts that transfer the legal rights associated with patents when the tokens are transferred. A partnership between IBM and IPwe has spearheaded the use of NFTs to secure patent ownership. These two companies have teamed together to build the infrastructure for an NFT-based patent marketplace.

Discussion

There are exciting proposals in the legal and economic literature that suggest seemingly straightforward solutions to many of the issues plaguing current patent systems. However, most solutions would constitute major administrative disruptions and place significant and continuous financial burdens on patent offices or their users. An NFT-based patents system not only makes many of these ideas administratively feasible but can also be examined in a step-wise, scalable, and very public manner.

Furthermore, NFT-based patents may facilitate reliable information sharing among offices and patentees worldwide, reducing the burden on examiners and perhaps even accelerating harmonization efforts. NFT-based patents also have additional transparency and archival attributes baked in. A patent should be a privilege bestowed on those who take resource-intensive risks to explore the frontier of technological capabilities. As a reward for their achievements, full transparency of these rewards is much public interest. It is a society that pays for administrative and economic inefficiencies that exist in today’s systems. NFT-based patents can enhance this transparency. From an organizational perspective, an NFT-based patent can remove current bottlenecks in patent processes by making these processes more efficient, rapid, and convenient for applicants without compromising the quality of granted patents.

The proposed framework encounters some challenges that should be solved to reach a developed patent verification platform. First, technical problems are discussed. The consensus method that is used in the verification layer is not addressed in detail. Due to the permissioned structure of miners in the NFT-based patents, consensus algorithms like PBFT, Federated Consensus, and Round Robin Consensus are designed for permissioned blockchains can be applied. Also, miners/validators spend some time validating the patents; hence a protocol should be designed to profit them. Some challenges like proving the miners’ time and effort, the price that inventors should pay to miners, and other economic trade-offs should be considered.

Different NFT standards were discussed. If various patent services use NFT standards, there will be some cross-platform problems. For instance, transferring an NFT from Ethereum blockchain (ERC-721 token) to EOS blockchain is not a forward and straight work and needs some considerations. Also, people usually trade NFTs in marketplaces such as Rarible and OpenSea. These marketplaces are centralized and may prompt some challenges because of their centralized nature. Besides, there exist some other types of challenges. For example, the novelty of NFT-based patents and blockchain services.

Blockchain-based patent service has not been tested before. The patent registration procedure and concepts of the Patent as NFT system may be ambiguous for people who still prefer conventional centralized patent systems over decentralized ones. It should be noted that there are some problems in the mining part. Miners should receive certificates from the accepted organizations. Determining these organizations and how they accept referees as validators need more consideration. Some types of inventions in some countries are prohibited, and inventors cannot register them. In NFT-based patents, inventors can register their patents publicly, and maybe some collisions occur between inventors and the government. There exist some misunderstandings about NFT’s ownership rights. It is not clear that when a person buys an NFT, which rights are given to them exactly; for instance, they have property rights or have moral rights, too.

Conclusion

Blockchain technology provides strong timestamping, the potential for smart contracts, proof-of-existence. It enables creating a transparent, distributed, cost-effective, and resilient environment that is open to all and where each transaction is auditable. On the other hand, blockchain is a definite boon to the IP industry, benefitting patent owners. When blockchain technology’s intrinsic characteristics are applied to the IP domain, it helps copyrights. This paper provided a conceptual framework for presenting an NFT-based patent with a comprehensive discussion of many aspects: background, model components, token standards to application areas, and research challenges. The proposed framework includes five main layers: Storage Layer, Authentication Layer, Verification Layer, Blockchain Layer, and Application. The primary purpose of this patent framework was to provide an NFT-based concept that could be used to patent a decentralized, anti-tamper, and reliable network for trade and exchange around the world. Finally, we addressed several open challenges to NFT-based inventions.

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Acknowledgements

This work has been partially supported by CAS President’s International Fellowship Initiative, China [grant number 2021VTB0002, 2021] and National Natural Science Foundation of China (No. 61902385).

Author information

Affiliations

  1. Department of Industrial Management, Yazd University, Yazd City, IranSeyed Mojtaba Hosseini Bamakan
  2. Department of Electrical and Computer Engineering, Isfahan University of Technology, Isfahan City, IranNasim Nezhadsistani
  3. School of Electrical and Computer Engineering, University of Tehran, Tehran City, IranOmid Bodaghi
  4. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, ChinaSeyed Mojtaba Hosseini Bamakan & Qiang Qu
  5. Huawei Blockchain Lab, Huawei Cloud Tech Co., Ltd., Shenzhen, ChinaQiang Qu

Contributions

NFT: Redefined Format of IP Assets

The collaboration between National Center for Advancing Translational Sciences (NCATS) at NIH and BurstIQ

2.0 LPBI is a Very Unique Organization 

 

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Reporter: Stephen J. Williams, Ph.D.

From: Heidi Rheim et al. GA4GH: International policies and standards for data sharing across genomic research and healthcare. (2021): Cell Genomics, Volume 1 Issue 2.

Source: DOI:https://doi.org/10.1016/j.xgen.2021.100029

Highlights

  • Siloing genomic data in institutions/jurisdictions limits learning and knowledge
  • GA4GH policy frameworks enable responsible genomic data sharing
  • GA4GH technical standards ensure interoperability, broad access, and global benefits
  • Data sharing across research and healthcare will extend the potential of genomics

Summary

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

In order for genomic and personalized medicine to come to fruition it is imperative that data siloes around the world are broken down, allowing the international collaboration for the collection, storage, transferring, accessing and analying of molecular and health-related data.

We had talked on this site in numerous articles about the problems data siloes produce. By data siloes we are meaning that collection and storage of not only DATA but intellectual thought are being held behind physical, electronic, and intellectual walls and inacessible to other scientisits not belonging either to a particular institituion or even a collaborative network.

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

Standardization and harmonization of data is key to this effort to sharing electronic records. The EU has taken bold action in this matter. The following section is about the General Data Protection Regulation of the EU and can be found at the following link:

https://ec.europa.eu/info/law/law-topic/data-protection/data-protection-eu_en

Fundamental rights

The EU Charter of Fundamental Rights stipulates that EU citizens have the right to protection of their personal data.

Protection of personal data

Legislation

The data protection package adopted in May 2016 aims at making Europe fit for the digital age. More than 90% of Europeans say they want the same data protection rights across the EU and regardless of where their data is processed.

The General Data Protection Regulation (GDPR)

Regulation (EU) 2016/679 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data. This text includes the corrigendum published in the OJEU of 23 May 2018.

The regulation is an essential step to strengthen individuals’ fundamental rights in the digital age and facilitate business by clarifying rules for companies and public bodies in the digital single market. A single law will also do away with the current fragmentation in different national systems and unnecessary administrative burdens.

The regulation entered into force on 24 May 2016 and applies since 25 May 2018. More information for companies and individuals.

Information about the incorporation of the General Data Protection Regulation (GDPR) into the EEA Agreement.

EU Member States notifications to the European Commission under the GDPR

The Data Protection Law Enforcement Directive

Directive (EU) 2016/680 on the protection of natural persons regarding processing of personal data connected with criminal offences or the execution of criminal penalties, and on the free movement of such data.

The directive protects citizens’ fundamental right to data protection whenever personal data is used by criminal law enforcement authorities for law enforcement purposes. It will in particular ensure that the personal data of victims, witnesses, and suspects of crime are duly protected and will facilitate cross-border cooperation in the fight against crime and terrorism.

The directive entered into force on 5 May 2016 and EU countries had to transpose it into their national law by 6 May 2018.

The following paper by the organiztion The Global Alliance for Genomics and Health discusses these types of collaborative efforts to break down data silos in personalized medicine. This organization has over 2000 subscribers in over 90 countries encompassing over 60 organizations.

Enabling responsible genomic data sharing for the benefit of human health

The Global Alliance for Genomics and Health (GA4GH) is a policy-framing and technical standards-setting organization, seeking to enable responsible genomic data sharing within a human rights framework.

he Global Alliance for Genomics and Health (GA4GH) is an international, nonprofit alliance formed in 2013 to accelerate the potential of research and medicine to advance human health. Bringing together 600+ leading organizations working in healthcare, research, patient advocacy, life science, and information technology, the GA4GH community is working together to create frameworks and standards to enable the responsible, voluntary, and secure sharing of genomic and health-related data. All of our work builds upon the Framework for Responsible Sharing of Genomic and Health-Related Data.

GA4GH Connect is a five-year strategic plan that aims to drive uptake of standards and frameworks for genomic data sharing within the research and healthcare communities in order to enable responsible sharing of clinical-grade genomic data by 2022. GA4GH Connect links our Work Streams with Driver Projects—real-world genomic data initiatives that help guide our development efforts and pilot our tools.

From the article on Cell Genomics GA4GH: International policies and standards for data sharing across genomic research and healthcare

Source: Open Access DOI:https://doi.org/10.1016/j.xgen.2021.100029PlumX Metrics

The Global Alliance for Genomics and Health (GA4GH) is a worldwide alliance of genomics researchers, data scientists, healthcare practitioners, and other stakeholders. We are collaborating to establish policy frameworks and technical standards for responsible, international sharing of genomic and other molecular data as well as related health data. Founded in 2013,3 the GA4GH community now consists of more than 1,000 individuals across more than 90 countries working together to enable broad sharing that transcends the boundaries of any single institution or country (see https://www.ga4gh.org).In this perspective, we present the strategic goals of GA4GH and detail current strategies and operational approaches to enable responsible sharing of clinical and genomic data, through both harmonized data aggregation and federated approaches, to advance genomic medicine and research. We describe technical and policy development activities of the eight GA4GH Work Streams and implementation activities across 24 real-world genomic data initiatives (“Driver Projects”). We review how GA4GH is addressing the major areas in which genomics is currently deployed including rare disease, common disease, cancer, and infectious disease. Finally, we describe differences between genomic sequence data that are generated for research versus healthcare purposes, and define strategies for meeting the unique challenges of responsibly enabling access to data acquired in the clinical setting.

GA4GH organization

GA4GH has partnered with 24 real-world genomic data initiatives (Driver Projects) to ensure its standards are fit for purpose and driven by real-world needs. Driver Projects make a commitment to help guide GA4GH development efforts and pilot GA4GH standards (see Table 2). Each Driver Project is expected to dedicate at least two full-time equivalents to GA4GH standards development, which takes place in the context of GA4GH Work Streams (see Figure 1). Work Streams are the key production teams of GA4GH, tackling challenges in eight distinct areas across the data life cycle (see Box 1). Work Streams consist of experts from their respective sub-disciplines and include membership from Driver Projects as well as hundreds of other organizations across the international genomics and health community.

Figure thumbnail gr1
Figure 1Matrix structure of the Global Alliance for Genomics and HealthShow full caption


Box 1
GA4GH Work Stream focus areasThe GA4GH Work Streams are the key production teams of the organization. Each tackles a specific area in the data life cycle, as described below (URLs listed in the web resources).

  • (1)Data use & researcher identities: Develops ontologies and data models to streamline global access to datasets generated in any country9,10
  • (2)Genomic knowledge standards: Develops specifications and data models for exchanging genomic variant observations and knowledge18
  • (3)Cloud: Develops federated analysis approaches to support the statistical rigor needed to learn from large datasets
  • (4)Data privacy & security: Develops guidelines and recommendations to ensure identifiable genomic and phenotypic data remain appropriately secure without sacrificing their analytic potential
  • (5)Regulatory & ethics: Develops policies and recommendations for ensuring individual-level data are interoperable with existing norms and follow core ethical principles
  • (6)Discovery: Develops data models and APIs to make data findable, accessible, interoperable, and reusable (FAIR)
  • (7)Clinical & phenotypic data capture & exchange: Develops data models to ensure genomic data is most impactful through rich metadata collected in a standardized way
  • (8)Large-scale genomics: Develops APIs and file formats to ensure harmonized technological platforms can support large-scale computing

For more articles on Open Access, Science 2.0, and Data Networks for Genomics on this Open Access Scientific Journal see:

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

Icelandic Population Genomic Study Results by deCODE Genetics come to Fruition: Curation of Current genomic studies

eScientific Publishing a Case in Point: Evolution of Platform Architecture Methodologies and of Intellectual Property Development (Content Creation by Curation) Business Model 

UK Biobank Makes Available 200,000 whole genomes Open Access

Systems Biology Analysis of Transcription Networks, Artificial Intelligence, and High-End Computing Coming to Fruition in Personalized Oncology

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UK Biobank Makes Available 200,000 whole genomes Open Access

Reporter: Stephen J. Williams, Ph.D.

The following is a summary of an article by Jocelyn Kaiser, published in the November 26, 2021 issue of the journal Science.

To see the full article please go to https://www.science.org/content/article/200-000-whole-genomes-made-available-biomedical-studies-uk-effort

The UK Biobank (UKBB) this week unveiled to scientists the entire genomes of 200,000 people who are part of a long-term British health study.

The trove of genomes, each linked to anonymized medical information, will allow biomedical scientists to scour the full 3 billion base pairs of human DNA for insights into the interplay of genes and health that could not be gleaned from partial sequences or scans of genome markers. “It is thrilling to see the release of this long-awaited resource,” says Stephen Glatt, a psychiatric geneticist at the State University of New York Upstate Medical University.

Other biobanks have also begun to compile vast numbers of whole genomes, 100,000 or more in some cases (see table, below). But UKBB stands out because it offers easy access to the genomic information, according to some of the more than 20,000 researchers in 90 countries who have signed up to use the data. “In terms of availability and data quality, [UKBB] surpasses all others,” says physician and statistician Omar Yaxmehen Bello-Chavolla of the National Institute for Geriatrics in Mexico City.

Enabling your vision to improve public health

Data drives discovery. We have curated a uniquely powerful biomedical database that can be accessed globally for public health research. Explore data from half a million UK Biobank participants to enable new discoveries to improve public health.

Data Showcase

Future data releases

This UKBB biobank represents genomes collected from 500,000 middle-age and elderly participants for 2006 to 2010. The genomes are mostly of a European descent. Other large scale genome sequencing ventures like Iceland’s DECODE, which collected over 100,000 genomes, is now a subsidiary of Amgen, and mostly behind IP protection, not Open Access as this database represents.

UK Biobank is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants. The database is regularly augmented with additional data and is globally accessible to approved researchers undertaking vital research into the most common and life-threatening diseases. It is a major contributor to the advancement of modern medicine and treatment and has enabled several scientific discoveries that improve human health.

A summary of some large scale genome sequencing projects are show in the table below:

BiobankCompleted Whole GenomesRelease Information
UK Biobank200,000300,000 more in early 2023
TransOmics for
Precision Medicien
161,000NIH requires project
specific request
Million Veterans
Program
125,000Non-Veterans Affairs
researchers get first access
100,000 Genomes
Project
120,000Researchers must join Genomics
England collaboration
All of Us90,000NIH expects to release 2022

Other Related Articles on Genome Biobank Projects in this Open Access Online Scientific Journal Include the Following:

Icelandic Population Genomic Study Results by deCODE Genetics come to Fruition: Curation of Current genomic studies

Exome Aggregation Consortium (ExAC), generated the largest catalogue so far of variation in human protein-coding regions: Sequence data of 60,000 people, NOW is a publicly accessible database

Systems Biology Analysis of Transcription Networks, Artificial Intelligence, and High-End Computing Coming to Fruition in Personalized Oncology

Diversity and Health Disparity Issues Need to be Addressed for GWAS and Precision Medicine Studies

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Developing Machine Learning Models for Prediction of Onset of Type-2 Diabetes

Reporter: Amandeep Kaur, B.Sc., M.Sc.

A recent study reports the development of an advanced AI algorithm which predicts up to five years in advance the starting of type 2 diabetes by utilizing regularly collected medical data. Researchers described their AI model as notable and distinctive based on the specific design which perform assessments at the population level.

The first author Mathieu Ravaut, M.Sc. of the University of Toronto and other team members stated that “The main purpose of our model was to inform population health planning and management for the prevention of diabetes that incorporates health equity. It was not our goal for this model to be applied in the context of individual patient care.”

Research group collected data from 2006 to 2016 of approximately 2.1 million patients treated at the same healthcare system in Ontario, Canada. Even though the patients were belonged to the same area, the authors highlighted that Ontario encompasses a diverse and large population.

The newly developed algorithm was instructed with data of approximately 1.6 million patients, validated with data of about 243,000 patients and evaluated with more than 236,000 patient’s data. The data used to improve the algorithm included the medical history of each patient from previous two years- prescriptions, medications, lab tests and demographic information.

When predicting the onset of type 2 diabetes within five years, the algorithm model reached a test area under the ROC curve of 80.26.

The authors reported that “Our model showed consistent calibration across sex, immigration status, racial/ethnic and material deprivation, and a low to moderate number of events in the health care history of the patient. The cohort was representative of the whole population of Ontario, which is itself among the most diverse in the world. The model was well calibrated, and its discrimination, although with a slightly different end goal, was competitive with results reported in the literature for other machine learning–based studies that used more granular clinical data from electronic medical records without any modifications to the original test set distribution.”

This model could potentially improve the healthcare system of countries equipped with thorough administrative databases and aim towards specific cohorts that may encounter the faulty outcomes.

Research group stated that “Because our machine learning model included social determinants of health that are known to contribute to diabetes risk, our population-wide approach to risk assessment may represent a tool for addressing health disparities.”

Sources:

https://www.cardiovascularbusiness.com/topics/prevention-risk-reduction/new-ai-model-healthcare-data-predict-type-2-diabetes?utm_source=newsletter

Reference:

Ravaut M, Harish V, Sadeghi H, et al. Development and Validation of a Machine Learning Model Using Administrative Health Data to Predict Onset of Type 2 Diabetes. JAMA Netw Open. 2021;4(5):e2111315. doi:10.1001/jamanetworkopen.2021.11315 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780137

Other related articles were published in this Open Access Online Scientific Journal, including the following:

AI in Drug Discovery: Data Science and Core Biology @Merck &Co, Inc., @GNS Healthcare, @QuartzBio, @Benevolent AI and Nuritas

Reporters: Aviva Lev-Ari, PhD, RN and Irina Robu, PhD

https://pharmaceuticalintelligence.com/2020/08/27/ai-in-drug-discovery-data-science-and-core-biology-merck-co-inc-gns-healthcare-quartzbio-benevolent-ai-and-nuritas/

Can Blockchain Technology and Artificial Intelligence Cure What Ails Biomedical Research and Healthcare

Curator: Stephen J. Williams, Ph.D.

https://pharmaceuticalintelligence.com/2018/12/10/can-blockchain-technology-and-artificial-intelligence-cure-what-ails-biomedical-research-and-healthcare/

HealthCare focused AI Startups from the 100 Companies Leading the Way in A.I. Globally

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/01/18/healthcare-focused-ai-startups-from-the-100-companies-leading-the-way-in-a-i-globally/

AI in Psychiatric Treatment – Using Machine Learning to Increase Treatment Efficacy in Mental Health

Reporter: Aviva Lev- Ari, PhD, RN

https://pharmaceuticalintelligence.com/2019/06/04/ai-in-psychiatric-treatment-using-machine-learning-to-increase-treatment-efficacy-in-mental-health/

Vyasa Analytics Demos Deep Learning Software for Life Sciences at Bio-IT World 2018 – Vyasa’s booth (#632)

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/05/10/vyasa-analytics-demos-deep-learning-software-for-life-sciences-at-bio-it-world-2018-vyasas-booth-632/

New Diabetes Treatment Using Smart Artificial Beta Cells

Reporter: Irina Robu, PhD

https://pharmaceuticalintelligence.com/2017/11/08/new-diabetes-treatment-using-smart-artificial-beta-cells/

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Systems Biology analysis of Transcription Networks, Artificial Intelligence, and High-End Computing Coming to Fruition in Personalized Oncology

Curator: Stephen J. Williams, Ph.D.

In the June 2020 issue of the journal Science, writer Roxanne Khamsi has an interesting article “Computing Cancer’s Weak Spots; An algorithm to unmask tumors’ molecular linchpins is tested in patients”[1], describing some early successes in the incorporation of cancer genome sequencing in conjunction with artificial intelligence algorithms toward a personalized clinical treatment decision for various tumor types.  In 2016, oncologists Amy Tiersten collaborated with systems biologist Andrea Califano and cell biologist Jose Silva at Mount Sinai Hospital to develop a systems biology approach to determine that the drug ruxolitinib, a STAT3 inhibitor, would be effective for one of her patient’s aggressively recurring, Herceptin-resistant breast tumor.  Dr. Califano, instead of defining networks of driver mutations, focused on identifying a few transcription factors that act as ‘linchpins’ or master controllers of transcriptional networks withing tumor cells, and in doing so hoping to, in essence, ‘bottleneck’ the transcriptional machinery of potential oncogenic products. As Dr. Castilano states

“targeting those master regulators and you will stop cancer in its tracks, no matter what mutation initially caused it.”

It is important to note that this approach also relies on the ability to sequence tumors  by RNA-seq to determine the underlying mutations which alter which master regulators are pertinent in any one tumor.  And given the wide tumor heterogeneity in tumor samples, this sequencing effort may have to involve multiple biopsies (as discussed in earlier posts on tumor heterogeneity in renal cancer).

As stated in the article, Califano co-founded a company called Darwin-Health in 2015 to guide doctors by identifying the key transcription factors in a patient’s tumor and suggesting personalized therapeutics to those identified molecular targets (OncoTarget™).  He had collaborated with the Jackson Laboratory and most recently Columbia University to conduct a $15 million 3000 patient clinical trial.  This was a bit of a stretch from his initial training as a physicist and, in 1986, IBM hired him for some artificial intelligence projects.  He then landed in 2003 at Columbia and has been working on identifying these transcriptional nodes that govern cancer survival and tumorigenicity.  Dr. Califano had figured that the number of genetic mutations which potentially could be drivers were too vast:

A 2018 study which analyzed more than 9000 tumor samples reported over 1.5 million mutations[2]

and impossible to develop therapeutics against.  He reasoned that you would just have to identify the common connections between these pathways or transcriptional nodes and termed them master regulators.

A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples

Chen H, Li C, Peng X, et al. Cell. 2018;173(2):386-399.e12.

Abstract

The role of enhancers, a key class of non-coding regulatory DNA elements, in cancer development has increasingly been appreciated. Here, we present the detection and characterization of a large number of expressed enhancers in a genome-wide analysis of 8928 tumor samples across 33 cancer types using TCGA RNA-seq data. Compared with matched normal tissues, global enhancer activation was observed in most cancers. Across cancer types, global enhancer activity was positively associated with aneuploidy, but not mutation load, suggesting a hypothesis centered on “chromatin-state” to explain their interplay. Integrating eQTL, mRNA co-expression, and Hi-C data analysis, we developed a computational method to infer causal enhancer-gene interactions, revealing enhancers of clinically actionable genes. Having identified an enhancer ∼140 kb downstream of PD-L1, a major immunotherapy target, we validated it experimentally. This study provides a systematic view of enhancer activity in diverse tumor contexts and suggests the clinical implications of enhancers.

 

A diagram of how concentrating on these transcriptional linchpins or nodes may be more therapeutically advantageous as only one pharmacologic agent is needed versus multiple agents to inhibit the various upstream pathways:

 

 

From: Khamsi R: Computing cancer’s weak spots. Science 2020, 368(6496):1174-1177.

 

VIPER Algorithm (Virtual Inference of Protein activity by Enriched Regulon Analysis)

The algorithm that Califano and DarwinHealth developed is a systems biology approach using a tumor’s RNASeq data to determine controlling nodes of transcription.  They have recently used the VIPER algorithm to look at RNA-Seq data from more than 10,000 tumor samples from TCGA and identified 407 transcription factor genes that acted as these linchpins across all tumor types.  Only 20 to 25 of  them were implicated in just one tumor type so these potential nodes are common in many forms of cancer.

Other institutions like the Cold Spring Harbor Laboratories have been using VIPER in their patient tumor analysis.  Linchpins for other tumor types have been found.  For instance, VIPER identified transcription factors IKZF1 and IKF3 as linchpins in multiple myeloma.  But currently approved therapeutics are hard to come by for targets with are transcription factors, as most pharma has concentrated on inhibiting an easier target like kinases and their associated activity.  In general, developing transcription factor inhibitors in more difficult an undertaking for multiple reasons.

Network-based inference of protein activity helps functionalize the genetic landscape of cancer. Alvarez MJ, Shen Y, Giorgi FM, Lachmann A, Ding BB, Ye BH, Califano A:. Nature genetics 2016, 48(8):838-847 [3]

Abstract

Identifying the multiple dysregulated oncoproteins that contribute to tumorigenesis in a given patient is crucial for developing personalized treatment plans. However, accurate inference of aberrant protein activity in biological samples is still challenging as genetic alterations are only partially predictive and direct measurements of protein activity are generally not feasible. To address this problem we introduce and experimentally validate a new algorithm, VIPER (Virtual Inference of Protein-activity by Enriched Regulon analysis), for the accurate assessment of protein activity from gene expression data. We use VIPER to evaluate the functional relevance of genetic alterations in regulatory proteins across all TCGA samples. In addition to accurately inferring aberrant protein activity induced by established mutations, we also identify a significant fraction of tumors with aberrant activity of druggable oncoproteins—despite a lack of mutations, and vice-versa. In vitro assays confirmed that VIPER-inferred protein activity outperforms mutational analysis in predicting sensitivity to targeted inhibitors.

 

 

 

 

Figure 1 

Schematic overview of the VIPER algorithm From: Alvarez MJ, Shen Y, Giorgi FM, Lachmann A, Ding BB, Ye BH, Califano A: Functional characterization of somatic mutations in cancer using network-based inference of protein activity. Nature genetics 2016, 48(8):838-847.

(a) Molecular layers profiled by different technologies. Transcriptomics measures steady-state mRNA levels; Proteomics quantifies protein levels, including some defined post-translational isoforms; VIPER infers protein activity based on the protein’s regulon, reflecting the abundance of the active protein isoform, including post-translational modifications, proper subcellular localization and interaction with co-factors. (b) Representation of VIPER workflow. A regulatory model is generated from ARACNe-inferred context-specific interactome and Mode of Regulation computed from the correlation between regulator and target genes. Single-sample gene expression signatures are computed from genome-wide expression data, and transformed into regulatory protein activity profiles by the aREA algorithm. (c) Three possible scenarios for the aREA analysis, including increased, decreased or no change in protein activity. The gene expression signature and its absolute value (|GES|) are indicated by color scale bars, induced and repressed target genes according to the regulatory model are indicated by blue and red vertical lines. (d) Pleiotropy Correction is performed by evaluating whether the enrichment of a given regulon (R4) is driven by genes co-regulated by a second regulator (R4∩R1). (e) Benchmark results for VIPER analysis based on multiple-samples gene expression signatures (msVIPER) and single-sample gene expression signatures (VIPER). Boxplots show the accuracy (relative rank for the silenced protein), and the specificity (fraction of proteins inferred as differentially active at p < 0.05) for the 6 benchmark experiments (see Table 2). Different colors indicate different implementations of the aREA algorithm, including 2-tail (2T) and 3-tail (3T), Interaction Confidence (IC) and Pleiotropy Correction (PC).

 Other articles from Andrea Califano on VIPER algorithm in cancer include:

Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state.

Echeverria GV, Ge Z, Seth S, Zhang X, Jeter-Jones S, Zhou X, Cai S, Tu Y, McCoy A, Peoples M, Sun Y, Qiu H, Chang Q, Bristow C, Carugo A, Shao J, Ma X, Harris A, Mundi P, Lau R, Ramamoorthy V, Wu Y, Alvarez MJ, Califano A, Moulder SL, Symmans WF, Marszalek JR, Heffernan TP, Chang JT, Piwnica-Worms H.Sci Transl Med. 2019 Apr 17;11(488):eaav0936. doi: 10.1126/scitranslmed.aav0936.PMID: 30996079

An Integrated Systems Biology Approach Identifies TRIM25 as a Key Determinant of Breast Cancer Metastasis.

Walsh LA, Alvarez MJ, Sabio EY, Reyngold M, Makarov V, Mukherjee S, Lee KW, Desrichard A, Turcan Ş, Dalin MG, Rajasekhar VK, Chen S, Vahdat LT, Califano A, Chan TA.Cell Rep. 2017 Aug 15;20(7):1623-1640. doi: 10.1016/j.celrep.2017.07.052.PMID: 28813674

Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers.

Rodriguez-Barrueco R, Yu J, Saucedo-Cuevas LP, Olivan M, Llobet-Navas D, Putcha P, Castro V, Murga-Penas EM, Collazo-Lorduy A, Castillo-Martin M, Alvarez M, Cordon-Cardo C, Kalinsky K, Maurer M, Califano A, Silva JM.Genes Dev. 2015 Aug 1;29(15):1631-48. doi: 10.1101/gad.262642.115. Epub 2015 Jul 30.PMID: 26227964

Master regulators used as breast cancer metastasis classifier.

Lim WK, Lyashenko E, Califano A.Pac Symp Biocomput. 2009:504-15.PMID: 19209726 Free

 

Additional References

 

  1. Khamsi R: Computing cancer’s weak spots. Science 2020, 368(6496):1174-1177.
  2. Chen H, Li C, Peng X, Zhou Z, Weinstein JN, Liang H: A Pan-Cancer Analysis of Enhancer Expression in Nearly 9000 Patient Samples. Cell 2018, 173(2):386-399 e312.
  3. Alvarez MJ, Shen Y, Giorgi FM, Lachmann A, Ding BB, Ye BH, Califano A: Functional characterization of somatic mutations in cancer using network-based inference of protein activity. Nature genetics 2016, 48(8):838-847.

 

Other articles of Note on this Open Access Online Journal Include:

Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

 

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Live Notes, Real Time Conference Coverage AACR 2020: Tuesday June 23, 2020 3:00 PM-5:30 PM Educational Sessions

Reporter: Stephen J. Williams, PhD

Follow Live in Real Time using

#AACR20

@pharma_BI

@AACR

Register for FREE at https://www.aacr.org/

uesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session
Tumor Biology, Bioinformatics and Systems Biology

The Clinical Proteomic Tumor Analysis Consortium: Resources and Data Dissemination

This session will provide information regarding methodologic and computational aspects of proteogenomic analysis of tumor samples, particularly in the context of clinical trials. Availability of comprehensive proteomic and matching genomic data for tumor samples characterized by the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) program will be described, including data access procedures and informatic tools under development. Recent advances on mass spectrometry-based targeted assays for inclusion in clinical trials will also be discussed.

Amanda G Paulovich, Shankha Satpathy, Meenakshi Anurag, Bing Zhang, Steven A Carr

Methods and tools for comprehensive proteogenomic characterization of bulk tumor to needle core biopsies

Shankha Satpathy
  • TCGA has 11,000 cancers with >20,000 somatic alterations but only 128 proteins as proteomics was still young field
  • CPTAC is NCI proteomic effort
  • Chemical labeling approach now method of choice for quantitative proteomics
  • Looked at ovarian and breast cancers: to measure PTM like phosphorylated the sample preparation is critical

 

Data access and informatics tools for proteogenomics analysis

Bing Zhang
  • Raw and processed data (raw MS data) with linked clinical data can be extracted in CPTAC
  • Python scripts are available for bioinformatic programming

 

Pathways to clinical translation of mass spectrometry-based assays

Meenakshi Anurag

·         Using kinase inhibitor pulldown (KIP) assay to identify unique kinome profiles

·         Found single strand break repair defects in endometrial luminal cases, especially with immune checkpoint prognostic tumors

·         Paper: JNCI 2019 analyzed 20,000 genes correlated with ET resistant in luminal B cases (selected for a list of 30 genes)

·         Validated in METABRIC dataset

·         KIP assay uses magnetic beads to pull out kinases to determine druggable kinases

·         Looked in xenografts and was able to pull out differential kinomes

·         Matched with PDX data so good clinical correlation

·         Were able to detect ESR1 fusion correlated with ER+ tumors

Tuesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session
Survivorship

Artificial Intelligence and Machine Learning from Research to the Cancer Clinic

The adoption of omic technologies in the cancer clinic is giving rise to an increasing number of large-scale high-dimensional datasets recording multiple aspects of the disease. This creates the need for frameworks for translatable discovery and learning from such data. Like artificial intelligence (AI) and machine learning (ML) for the cancer lab, methods for the clinic need to (i) compare and integrate different data types; (ii) scale with data sizes; (iii) prove interpretable in terms of the known biology and batch effects underlying the data; and (iv) predict previously unknown experimentally verifiable mechanisms. Methods for the clinic, beyond the lab, also need to (v) produce accurate actionable recommendations; (vi) prove relevant to patient populations based upon small cohorts; and (vii) be validated in clinical trials. In this educational session we will present recent studies that demonstrate AI and ML translated to the cancer clinic, from prognosis and diagnosis to therapy.
NOTE: Dr. Fish’s talk is not eligible for CME credit to permit the free flow of information of the commercial interest employee participating.

Ron C. Anafi, Rick L. Stevens, Orly Alter, Guy Fish

Overview of AI approaches in cancer research and patient care

Rick L. Stevens
  • Deep learning is less likely to saturate as data increases
  • Deep learning attempts to learn multiple layers of information
  • The ultimate goal is prediction but this will be the greatest challenge for ML
  • ML models can integrate data validation and cross database validation
  • What limits the performance of cross validation is the internal noise of data (reproducibility)
  • Learning curves: not the more data but more reproducible data is important
  • Neural networks can outperform classical methods
  • Important to measure validation accuracy in training set. Class weighting can assist in development of data set for training set especially for unbalanced data sets

Discovering genome-scale predictors of survival and response to treatment with multi-tensor decompositions

Orly Alter
  • Finding patterns using SVD component analysis. Gene and SVD patterns match 1:1
  • Comparative spectral decompositions can be used for global datasets
  • Validation of CNV data using this strategy
  • Found Ras, Shh and Notch pathways with altered CNV in glioblastoma which correlated with prognosis
  • These predictors was significantly better than independent prognostic indicator like age of diagnosis

 

Identifying targets for cancer chronotherapy with unsupervised machine learning

Ron C. Anafi
  • Many clinicians have noticed that some patients do better when chemo is given at certain times of the day and felt there may be a circadian rhythm or chronotherapeutic effect with respect to side effects or with outcomes
  • ML used to determine if there is indeed this chronotherapy effect or can we use unstructured data to determine molecular rhythms?
  • Found a circadian transcription in human lung
  • Most dataset in cancer from one clinical trial so there might need to be more trials conducted to take into consideration circadian rhythms

Stratifying patients by live-cell biomarkers with random-forest decision trees

Stratifying patients by live-cell biomarkers with random-forest decision trees

Guy Fish CEO Cellanyx Diagnostics

 

Tuesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session
Tumor Biology, Molecular and Cellular Biology/Genetics, Bioinformatics and Systems Biology, Prevention Research

The Wound Healing that Never Heals: The Tumor Microenvironment (TME) in Cancer Progression

This educational session focuses on the chronic wound healing, fibrosis, and cancer “triad.” It emphasizes the similarities and differences seen in these conditions and attempts to clarify why sustained fibrosis commonly supports tumorigenesis. Importance will be placed on cancer-associated fibroblasts (CAFs), vascularity, extracellular matrix (ECM), and chronic conditions like aging. Dr. Dvorak will provide an historical insight into the triad field focusing on the importance of vascular permeability. Dr. Stewart will explain how chronic inflammatory conditions, such as the aging tumor microenvironment (TME), drive cancer progression. The session will close with a review by Dr. Cukierman of the roles that CAFs and self-produced ECMs play in enabling the signaling reciprocity observed between fibrosis and cancer in solid epithelial cancers, such as pancreatic ductal adenocarcinoma.

Harold F Dvorak, Sheila A Stewart, Edna Cukierman

 

The importance of vascular permeability in tumor stroma generation and wound healing

Harold F Dvorak

Aging in the driver’s seat: Tumor progression and beyond

Sheila A Stewart

Why won’t CAFs stay normal?

Edna Cukierman

 

Tuesday, June 23

3:00 PM – 5:00 PM EDT

 

 

 

 

 

 

 

Other Articles on this Open Access  Online Journal on Cancer Conferences and Conference Coverage in Real Time Include

Press Coverage
Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Symposium: New Drugs on the Horizon Part 3 12:30-1:25 PM
Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on NCI Activities: COVID-19 and Cancer Research 5:20 PM
Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Evaluating Cancer Genomics from Normal Tissues Through Metastatic Disease 3:50 PM
Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Novel Targets and Therapies 2:35 PM

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Live Notes, Real Time Conference Coverage AACR 2020 #AACR20: Tuesday June 23, 2020 Noon-2:45 Educational Sessions

Live Notes, Real Time Conference Coverage AACR 2020: Tuesday June 23, 2020 Noon-2:45 Educational Sessions

Reporter: Stephen J. Williams, PhD

Follow Live in Real Time using

#AACR20

@pharma_BI

@AACR

Register for FREE at https://www.aacr.org/

 

Presidential Address

Elaine R Mardis, William N Hait

DETAILS

Welcome and introduction

William N Hait

 

Improving diagnostic yield in pediatric cancer precision medicine

Elaine R Mardis
  • Advent of genomics have revolutionized how we diagnose and treat lung cancer
  • We are currently needing to understand the driver mutations and variants where we can personalize therapy
  • PD-L1 and other checkpoint therapy have not really been used in pediatric cancers even though CAR-T have been successful
  • The incidence rates and mortality rates of pediatric cancers are rising
  • Large scale study of over 700 pediatric cancers show cancers driven by epigenetic drivers or fusion proteins. Need for transcriptomics.  Also study demonstrated that we have underestimated germ line mutations and hereditary factors.
  • They put together a database to nominate patients on their IGM Cancer protocol. Involves genetic counseling and obtaining germ line samples to determine hereditary factors.  RNA and protein are evaluated as well as exome sequencing. RNASeq and Archer Dx test to identify driver fusions
  • PECAN curated database from St. Jude used to determine driver mutations. They use multiple databases and overlap within these databases and knowledge base to determine or weed out false positives
  • They have used these studies to understand the immune infiltrate into recurrent cancers (CytoCure)
  • They found 40 germline cancer predisposition genes, 47 driver somatic fusion proteins, 81 potential actionable targets, 106 CNV, 196 meaningful somatic driver mutations

 

 

Tuesday, June 23

12:00 PM – 12:30 PM EDT

Awards and Lectures

NCI Director’s Address

Norman E Sharpless, Elaine R Mardis

DETAILS

Introduction: Elaine Mardis

 

NCI Director Address: Norman E Sharpless
  • They are functioning well at NCI with respect to grant reviews, research, and general functions in spite of the COVID pandemic and the massive demonstrations on also focusing on the disparities which occur in cancer research field and cancer care
  • There are ongoing efforts at NCI to make a positive difference in racial injustice, diversity in the cancer workforce, and for patients as well
  • Need a diverse workforce across the cancer research and care spectrum
  • Data show that areas where the clinicians are successful in putting African Americans on clinical trials are areas (geographic and site specific) where health disparities are narrowing
  • Grants through NCI new SeroNet for COVID-19 serologic testing funded by two RFAs through NIAD (RFA-CA-30-038 and RFA-CA-20-039) and will close on July 22, 2020

 

Tuesday, June 23

12:45 PM – 1:46 PM EDT

Virtual Educational Session

Immunology, Tumor Biology, Experimental and Molecular Therapeutics, Molecular and Cellular Biology/Genetics

Tumor Immunology and Immunotherapy for Nonimmunologists: Innovation and Discovery in Immune-Oncology

This educational session will update cancer researchers and clinicians about the latest developments in the detailed understanding of the types and roles of immune cells in tumors. It will summarize current knowledge about the types of T cells, natural killer cells, B cells, and myeloid cells in tumors and discuss current knowledge about the roles these cells play in the antitumor immune response. The session will feature some of the most promising up-and-coming cancer immunologists who will inform about their latest strategies to harness the immune system to promote more effective therapies.

Judith A Varner, Yuliya Pylayeva-Gupta

 

Introduction

Judith A Varner
New techniques reveal critical roles of myeloid cells in tumor development and progression
  • Different type of cells are becoming targets for immune checkpoint like myeloid cells
  • In T cell excluded or desert tumors T cells are held at periphery so myeloid cells can infiltrate though so macrophages might be effective in these immune t cell naïve tumors, macrophages are most abundant types of immune cells in tumors
  • CXCLs are potential targets
  • PI3K delta inhibitors,
  • Reduce the infiltrate of myeloid tumor suppressor cells like macrophages
  • When should we give myeloid or T cell therapy is the issue
Judith A Varner
Novel strategies to harness T-cell biology for cancer therapy
Positive and negative roles of B cells in cancer
Yuliya Pylayeva-Gupta
New approaches in cancer immunotherapy: Programming bacteria to induce systemic antitumor immunity

 

 

Tuesday, June 23

12:45 PM – 1:46 PM EDT

Virtual Educational Session

Cancer Chemistry

Chemistry to the Clinic: Part 2: Irreversible Inhibitors as Potential Anticancer Agents

There are numerous examples of highly successful covalent drugs such as aspirin and penicillin that have been in use for a long period of time. Despite historical success, there was a period of reluctance among many to purse covalent drugs based on concerns about toxicity. With advances in understanding features of a well-designed covalent drug, new techniques to discover and characterize covalent inhibitors, and clinical success of new covalent cancer drugs in recent years, there is renewed interest in covalent compounds. This session will provide a broad look at covalent probe compounds and drug development, including a historical perspective, examination of warheads and electrophilic amino acids, the role of chemoproteomics, and case studies.

Benjamin F Cravatt, Richard A. Ward, Sara J Buhrlage

 

Discovering and optimizing covalent small-molecule ligands by chemical proteomics

Benjamin F Cravatt
  • Multiple approaches are being investigated to find new covalent inhibitors such as: 1) cysteine reactivity mapping, 2) mapping cysteine ligandability, 3) and functional screening in phenotypic assays for electrophilic compounds
  • Using fluorescent activity probes in proteomic screens; have broad useability in the proteome but can be specific
  • They screened quiescent versus stimulated T cells to determine reactive cysteines in a phenotypic screen and analyzed by MS proteomics (cysteine reactivity profiling); can quantitate 15000 to 20,000 reactive cysteines
  • Isocitrate dehydrogenase 1 and adapter protein LCP-1 are two examples of changes in reactive cysteines they have seen using this method
  • They use scout molecules to target ligands or proteins with reactive cysteines
  • For phenotypic screens they first use a cytotoxic assay to screen out toxic compounds which just kill cells without causing T cell activation (like IL10 secretion)
  • INTERESTINGLY coupling these MS reactive cysteine screens with phenotypic screens you can find NONCANONICAL mechanisms of many of these target proteins (many of the compounds found targets which were not predicted or known)

Electrophilic warheads and nucleophilic amino acids: A chemical and computational perspective on covalent modifier

The covalent targeting of cysteine residues in drug discovery and its application to the discovery of Osimertinib

Richard A. Ward
  • Cysteine activation: thiolate form of cysteine is a strong nucleophile
  • Thiolate form preferred in polar environment
  • Activation can be assisted by neighboring residues; pKA will have an effect on deprotonation
  • pKas of cysteine vary in EGFR
  • cysteine that are too reactive give toxicity while not reactive enough are ineffective

 

Accelerating drug discovery with lysine-targeted covalent probes

 

Tuesday, June 23

12:45 PM – 2:15 PM EDT

Virtual Educational Session

Molecular and Cellular Biology/Genetics

Virtual Educational Session

Tumor Biology, Immunology

Metabolism and Tumor Microenvironment

This Educational Session aims to guide discussion on the heterogeneous cells and metabolism in the tumor microenvironment. It is now clear that the diversity of cells in tumors each require distinct metabolic programs to survive and proliferate. Tumors, however, are genetically programmed for high rates of metabolism and can present a metabolically hostile environment in which nutrient competition and hypoxia can limit antitumor immunity.

Jeffrey C Rathmell, Lydia Lynch, Mara H Sherman, Greg M Delgoffe

 

T-cell metabolism and metabolic reprogramming antitumor immunity

Jeffrey C Rathmell

Introduction

Jeffrey C Rathmell

Metabolic functions of cancer-associated fibroblasts

Mara H Sherman

Tumor microenvironment metabolism and its effects on antitumor immunity and immunotherapeutic response

Greg M Delgoffe
  • Multiple metabolites, reactive oxygen species within the tumor microenvironment; is there heterogeneity within the TME metabolome which can predict their ability to be immunosensitive
  • Took melanoma cells and looked at metabolism using Seahorse (glycolysis): and there was vast heterogeneity in melanoma tumor cells; some just do oxphos and no glycolytic metabolism (inverse Warburg)
  • As they profiled whole tumors they could separate out the metabolism of each cell type within the tumor and could look at T cells versus stromal CAFs or tumor cells and characterized cells as indolent or metabolic
  • T cells from hyerglycolytic tumors were fine but from high glycolysis the T cells were more indolent
  • When knock down glucose transporter the cells become more glycolytic
  • If patient had high oxidative metabolism had low PDL1 sensitivity
  • Showed this result in head and neck cancer as well
  • Metformin a complex 1 inhibitor which is not as toxic as most mito oxphos inhibitors the T cells have less hypoxia and can remodel the TME and stimulate the immune response
  • Metformin now in clinical trials
  • T cells though seem metabolically restricted; T cells that infiltrate tumors are low mitochondrial phosph cells
  • T cells from tumors have defective mitochondria or little respiratory capacity
  • They have some preliminary findings that metabolic inhibitors may help with CAR-T therapy

Obesity, lipids and suppression of anti-tumor immunity

Lydia Lynch
  • Hypothesis: obesity causes issues with anti tumor immunity
  • Less NK cells in obese people; also produce less IFN gamma
  • RNASeq on NOD mice; granzymes and perforins at top of list of obese downregulated
  • Upregulated genes that were upregulated involved in lipid metabolism
  • All were PPAR target genes
  • NK cells from obese patients takes up palmitate and this reduces their glycolysis but OXPHOS also reduced; they think increased FFA basically overloads mitochondria
  • PPAR alpha gamma activation mimics obesity

 

 

Tuesday, June 23

12:45 PM – 2:45 PM EDT

Virtual Educational Session

Clinical Research Excluding Trials

The Evolving Role of the Pathologist in Cancer Research

Long recognized for their role in cancer diagnosis and prognostication, pathologists are beginning to leverage a variety of digital imaging technologies and computational tools to improve both clinical practice and cancer research. Remarkably, the emergence of artificial intelligence (AI) and machine learning algorithms for analyzing pathology specimens is poised to not only augment the resolution and accuracy of clinical diagnosis, but also fundamentally transform the role of the pathologist in cancer science and precision oncology. This session will discuss what pathologists are currently able to achieve with these new technologies, present their challenges and barriers, and overview their future possibilities in cancer diagnosis and research. The session will also include discussions of what is practical and doable in the clinic for diagnostic and clinical oncology in comparison to technologies and approaches primarily utilized to accelerate cancer research.

 

Jorge S Reis-Filho, Thomas J Fuchs, David L Rimm, Jayanta Debnath

DETAILS

Tuesday, June 23

12:45 PM – 2:45 PM EDT

 

High-dimensional imaging technologies in cancer research

David L Rimm

  • Using old methods and new methods; so cell counting you use to find the cells then phenotype; with quantification like with Aqua use densitometry of positive signal to determine a threshold to determine presence of a cell for counting
  • Hiplex versus multiplex imaging where you have ten channels to measure by cycling of flour on antibody (can get up to 20plex)
  • Hiplex can be coupled with Mass spectrometry (Imaging Mass spectrometry, based on heavy metal tags on mAbs)
  • However it will still take a trained pathologist to define regions of interest or field of desired view

 

Introduction

Jayanta Debnath

Challenges and barriers of implementing AI tools for cancer diagnostics

Jorge S Reis-Filho

Implementing robust digital pathology workflows into clinical practice and cancer research

Jayanta Debnath

Invited Speaker

Thomas J Fuchs
  • Founder of spinout of Memorial Sloan Kettering
  • Separates AI from computational algothimic
  • Dealing with not just machines but integrating human intelligence
  • Making decision for the patients must involve human decision making as well
  • How do we get experts to do these decisions faster
  • AI in pathology: what is difficult? =è sandbox scenarios where machines are great,; curated datasets; human decision support systems or maps; or try to predict nature
  • 1) learn rules made by humans; human to human scenario 2)constrained nature 3)unconstrained nature like images and or behavior 4) predict nature response to nature response to itself
  • In sandbox scenario the rules are set in stone and machines are great like chess playing
  • In second scenario can train computer to predict what a human would predict
  • So third scenario is like driving cars
  • System on constrained nature or constrained dataset will take a long time for commuter to get to decision
  • Fourth category is long term data collection project
  • He is finding it is still finding it is still is difficult to predict nature so going from clinical finding to prognosis still does not have good predictability with AI alone; need for human involvement
  • End to end partnering (EPL) is a new way where humans can get more involved with the algorithm and assist with the problem of constrained data
  • An example of a workflow for pathology would be as follows from Campanella et al 2019 Nature Medicine: obtain digital images (they digitized a million slides), train a massive data set with highthroughput computing (needed a lot of time and big software developing effort), and then train it using input be the best expert pathologists (nature to human and unconstrained because no data curation done)
  • Led to first clinically grade machine learning system (Camelyon16 was the challenge for detecting metastatic cells in lymph tissue; tested on 12,000 patients from 45 countries)
  • The first big hurdle was moving from manually annotated slides (which was a big bottleneck) to automatically extracted data from path reports).
  • Now problem is in prediction: How can we bridge the gap from predicting humans to predicting nature?
  • With an AI system pathologist drastically improved the ability to detect very small lesions

 

Virtual Educational Session

Epidemiology

Cancer Increases in Younger Populations: Where Are They Coming from?

Incidence rates of several cancers (e.g., colorectal, pancreatic, and breast cancers) are rising in younger populations, which contrasts with either declining or more slowly rising incidence in older populations. Early-onset cancers are also more aggressive and have different tumor characteristics than those in older populations. Evidence on risk factors and contributors to early-onset cancers is emerging. In this Educational Session, the trends and burden, potential causes, risk factors, and tumor characteristics of early-onset cancers will be covered. Presenters will focus on colorectal and breast cancer, which are among the most common causes of cancer deaths in younger people. Potential mechanisms of early-onset cancers and racial/ethnic differences will also be discussed.

Stacey A. Fedewa, Xavier Llor, Pepper Jo Schedin, Yin Cao

Cancers that are and are not increasing in younger populations

Stacey A. Fedewa

 

  • Early onset cancers, pediatric cancers and colon cancers are increasing in younger adults
  • Younger people are more likely to be uninsured and these are there most productive years so it is a horrible life event for a young adult to be diagnosed with cancer. They will have more financial hardship and most (70%) of the young adults with cancer have had financial difficulties.  It is very hard for women as they are on their childbearing years so additional stress
  • Types of early onset cancer varies by age as well as geographic locations. For example in 20s thyroid cancer is more common but in 30s it is breast cancer.  Colorectal and testicular most common in US.
  • SCC is decreasing by adenocarcinoma of the cervix is increasing in women’s 40s, potentially due to changing sexual behaviors
  • Breast cancer is increasing in younger women: maybe etiologic distinct like triple negative and larger racial disparities in younger African American women
  • Increased obesity among younger people is becoming a factor in this increasing incidence of early onset cancers

 

 

Other Articles on this Open Access  Online Journal on Cancer Conferences and Conference Coverage in Real Time Include

Press Coverage

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Symposium: New Drugs on the Horizon Part 3 12:30-1:25 PM

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on NCI Activities: COVID-19 and Cancer Research 5:20 PM

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Evaluating Cancer Genomics from Normal Tissues Through Metastatic Disease 3:50 PM

Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Novel Targets and Therapies 2:35 PM

 

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Powerful AI Tools Being Developed for the COVID-19 Fight

Curator: Stephen J. Williams, Ph.D.

 

Source: https://www.ibm.com/blogs/research/2020/04/ai-powered-technologies-accelerate-discovery-covid-19/

IBM Releases Novel AI-Powered Technologies to Help Health and Research Community Accelerate the Discovery of Medical Insights and Treatments for COVID-19

April 3, 2020 | Written by: 

IBM Research has been actively developing new cloud and AI-powered technologies that can help researchers across a variety of scientific disciplines accelerate the process of discovery. As the COVID-19 pandemic unfolds, we continue to ask how these technologies and our scientific knowledge can help in the global battle against coronavirus.

Today, we are making available multiple novel, free resources from across IBM to help healthcare researchers, doctors and scientists around the world accelerate COVID-19 drug discovery: from gathering insights, to applying the latest virus genomic information and identifying potential targets for treatments, to creating new drug molecule candidates.

Though some of the resources are still in exploratory stages, IBM is making them available to qualifying researchers at no charge to aid the international scientific investigation of COVID-19.

Today’s announcement follows our recent leadership in launching the U.S. COVID-19 High Performance Computing Consortium, which is harnessing massive computing power in the effort to help confront the coronavirus.

Streamlining the Search for Information

Healthcare agencies and governments around the world have quickly amassed medical and other relevant data about the pandemic. And, there are already vast troves of medical research that could prove relevant to COVID-19. Yet, as with any large volume of disparate data sources, it is difficult to efficiently aggregate and analyze that data in ways that can yield scientific insights.

To help researchers access structured and unstructured data quickly, we are offering a cloud-based AI research resource that has been trained on a corpus of thousands of scientific papers contained in the COVID-19 Open Research Dataset (CORD-19), prepared by the White House and a coalition of research groups, and licensed databases from the DrugBankClinicaltrials.gov and GenBank. This tool uses our advanced AI and allows researchers to pose specific queries to the collections of papers and to extract critical COVID-19 knowledge quickly. Please note, access to this resource will be granted only to qualified researchers. To learn more and request access, please click here.

Aiding the Hunt for Treatments

The traditional drug discovery pipeline relies on a library of compounds that are screened, improved, and tested to determine safety and efficacy. In dealing with new pathogens such as SARS-CoV-2, there is the potential to enhance the compound libraries with additional novel compounds. To help address this need, IBM Research has recently created a new, AI-generative framework which can rapidly identify novel peptides, proteins, drug candidates and materials.

We have applied this AI technology against three COVID-19 targets to identify 3,000 new small molecules as potential COVID-19 therapeutic candidates. IBM is releasing these molecules under an open license, and researchers can study them via a new interactive molecular explorer tool to understand their characteristics and relationship to COVID-19 and identify candidates that might have desirable properties to be further pursued in drug development.

To streamline efforts to identify new treatments for COVID-19, we are also making the IBM Functional Genomics Platform available for free for the duration of the pandemic. Built to discover the molecular features in viral and bacterial genomes, this cloud-based repository and research tool includes genes, proteins and other molecular targets from sequenced viral and bacterial organisms in one place with connections pre-computed to help accelerate discovery of molecular targets required for drug design, test development and treatment.

Select IBM collaborators from government agencies, academic institutions and other organizations already use this platform for bacterial genomic study. And now, those working on COVID-19 can request the IBM Functional Genomics Platform interface to explore the genomic features of the virus. Access to the IBM Functional Genomics Platform will be prioritized for those conducting COVID-19 research. To learn more and request access, please click here.

Drug and Disease Information

Clinicians and healthcare professionals on the frontlines of care will also have free access to hundreds of pieces of evidence-based, curated COVID-19 and infectious disease content from IBM Micromedex and EBSCO DynaMed. Using these two rich decision support solutions, users will have access to drug and disease information in a single and comprehensive search. Clinicians can also provide patients with consumer-friendly patient education handouts with relevant, actionable medical information. IBM Micromedex is one of the largest online reference databases for medication information and is used by more than 4,500 hospitals and health systems worldwide. EBSCO DynaMed provides peer-reviewed clinical content, including systematic literature reviews in 28 specialties for comprehensive disease topics, health conditions and abnormal findings, to highly focused topics on evaluation, differential diagnosis and management.

The scientific community is working hard to make important new discoveries relevant to the treatment of COVID-19, and we’re hopeful that releasing these novel tools will help accelerate this global effort. This work also outlines our long-term vision for the future of accelerated discovery, where multi-disciplinary scientists and clinicians work together to rapidly and effectively create next generation therapeutics, aided by novel AI-powered technologies.

Learn more about IBM’s response to COVID-19: IBM.com/COVID19.

Source: https://www.ibm.com/blogs/research/2020/04/ai-powered-technologies-accelerate-discovery-covid-19/

DiA Imaging Analysis Receives Grant to Accelerate Global Access to its AI Ultrasound Solutions in the Fight Against COVID-19

Source: https://www.grantnews.com/news-articles/?rkey=20200512UN05506&filter=12337

Grant will allow company to accelerate access to its AI solutions and use of ultrasound in COVID-19 emergency settings

TEL AVIV, IsraelMay 12, 2020 /PRNewswire-PRWeb/ — DiA Imaging Analysis, a leading provider of AI based ultrasound analysis solutions, today announced that it has received a government grant from the Israel Innovation Authority (IIA) to develop solutions for ultrasound imaging analysis of COVID-19 patients using Artificial Intelligence (AI).Using ultrasound in point of care emergency settings has gained momentum since the outbreak of COVID-19 pandemic. In these settings, which include makeshift hospital COVID-19 departments and triage “tents,” portable ultrasound offers clinicians diagnostic decision support, with the added advantage of being easier to disinfect and eliminating the need to transport patients from one room to another.However, analyzing ultrasound images is a process that it is still mostly done visually, leading to a growing market need for automated solutions and decision support.As the leading provider of AI solutions for ultrasound analysis and backed by Connecticut Innovations, DiA makes ultrasound analysis smarter and accessible to both new and expert ultrasound users with various levels of experience. The company’s flagship LVivo Cardio Toolbox for AI-based cardiac ultrasound analysis enables clinicians to automatically generate objective clinical analysis, with increased accuracy and efficiency to support decisions about patient treatment and care.

The IIA grant provides a budget of millions NIS to increase access to DiA’s solutions for users in Israel and globally, and accelerate R&D with a focus on new AI solutions for COVID-19 patient management. DiA solutions are vendor-neutral and platform agnostic, as well as powered to run in low processing, mobile environments like handheld ultrasound.Recent data highlights the importance of looking at the heart during the progression of COVID-19, with one study citing 20% of patients hospitalized with COVID-19 showing signs of heart damage and increased mortality rates in those patients. DiA’s LVivo cardiac analysis solutions automatically generate objective, quantified cardiac ultrasound results to enable point-of-care clinicians to assess cardiac function on the spot, near patients’ bedside.

According to Dr. Ami Applebaum, the Chairman of the Board of the IIA, “The purpose of IIA’s call was to bring solutions to global markets for fighting COVID-19, with an emphasis on relevancy, fast time to market and collaborations promising continuity of the Israeli economy. DiA meets these requirements with AI innovation for ultrasound.”DiA has received several FDA/CE clearances and established distribution partnerships with industry leading companies including GE Healthcare, IBM Watson and Konica Minolta, currently serving thousands of end users worldwide.”We see growing use of ultrasound in point of care settings, and an urgent need for automated, objective solutions that provide decision support in real time,” said Hila Goldman-Aslan, CEO and Co-founder of DiA Imaging Analysis, “Our AI solutions meet this need by immediately helping clinicians on the frontlines to quickly and easily assess COVID-19 patients’ hearts to help guide care delivery.”

About DiA Imaging Analysis:
DiA Imaging Analysis provides advanced AI-based ultrasound analysis technology that makes ultrasound accessible to all. DiA’s automated tools deliver fast and accurate clinical indications to support the decision-making process and offer better patient care. DiA’s AI-based technology uses advanced pattern recognition and machine-learning algorithms to automatically imitate the way the human eye detects image borders and identifies motion. Using DiA’s tools provides automated and objective AI tools, helps reduce variability among users, and increases efficiency. It allows clinicians with various levels of experience to quickly and easily analyze ultrasound images.

For additional information, please visit http://www.dia-analysis.com.

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