Healthcare analytics, AI solutions for biological big data, providing an AI platform for the biotech, life sciences, medical and pharmaceutical industries, as well as for related technological approaches, i.e., curation and text analysis with machine learning and other activities related to AI applications to these industries.
Biological data is complex. Possibly some of the most complex genomics data is that which tries to capture the RNA, or transcriptome, that is active in a sample. A central theme to our research and development is representing large complex data in new ways in order to aid in assessment and discovery. Below are 3 pictures that tell a story of transcriptomes and in my opinion do so in a way that can not be as effectively told in either text or numbers. Enjoy.
A. microRNA in mouse model of disease
B. Transcription of Fungal pathogen prior and post infection of wheat host
C. Biological Replicates of Algal strains.
(1) MicroRNA in mouse model of disease. Best Behaved. Replicates are usually well behaved, but this experiment showed just how well behaved things could be. A sharp spire over 5 orders of magnitude.
(2) Transcription of Fungal pathogen prior and post infection of wheat host. A picture of Discovery! This is a favorite for two reasons, one because it is the result of a comparative expression study using a transcriptome assembly we built for the project (ie no genome necessary) and two because it shows a clustering of genes showing differential expression (70% of which were previously implicated in other studies). A beautiful picture of expression that resulted in a great publication:
Bruce M, Neugebauer KA, Joly DL, Migeon P, Cuomo CA, Wang S, Akhunov E,
Bakkeren G, Kolmer JA, Fellers JP. Using transcription of six Puccinia triticina
races to identify the effective secretome during infection of wheat. Front Plant
Sci. 2014 Jan 13;4:520. doi: 10.3389/fpls.2013.00520. eCollection 2014 Jan 13.
PubMed PMID: 24454317; PubMed Central PMCID: PMC3888938.
(3) Biological Replicates of Algal strains. Biology can be messy. This project reminds me that transcriptomes can be complex (especially when you fish it out of a pond), and therefore you have to understand complexity and variability of the transcriptome(s) before thinking you can find the one gene or pathway responsible for the difference in phenotype.
Related
6 Changes That’ll Make a Big Difference With Your RNA-seq; Part 6
6 Changes That’ll Make a Big Difference With Your RNA-seq; Part 2
6 Changes That’ll Make a Big Difference With Your RNA-seq; Part 1
CSHL, UCLA & Einstein to Lead Roundtable Discussions on Single-Cell Sequencing
Interactive discussions on three of the key questions researchers are facing when considering single-cell analysis will be held on the second day of the Single-Cell Sequencing Conference at Next Generation Dx Summit, taking place August 20-21, 2014 in Washington, DC. For full program details and to register, please visit NextGenerationDx.com/Single-Cell-Sequencing.Making Single-Cell Analysis Cost Effective for Clinical Use
Moderator: James Hicks, Ph.D., Research Professor, Cancer Genomics, Cold Spring Harbor Laboratory
Methods for capture: What are the tradeoffs?
Combining RNA, DNA and protein analysis
What genomic assays are most informative?
Can assays be certifiable?
Finding a Needle in a Haystack: Towards Diagnosing Rare Soft Tissue Cancer Stem Cells (CSCs) Moderator: Michael Masterman-Smith, Ph.D., Entrepreneurial Scientist, UCLA California NanoSystems Institute
Rethinking companion diagnostics for cancer to incorporate analysis of CSCs
Current direct methodologies of CSC detection/isolation
Current proxy methodologies of CSC detection/isolation
The hope and promise of single-cell assay tools and technologies
Why Single-Cell Sequencing? Moderator: Jan Vijg, Ph.D., Professor and Chairman, Genetics, Albert Einstein College of Medicine
Sample limitations, e.g., prenatal diagnostics and CTCs
Sample limitations, e.g., prenatal diagnostics and CTCs
To study cell-to-cell variation, e.g., in tumors as well as normal tissues
To overcome technological constraints, e.g., detecting somatic mutations
Cell-to-cell fluctuations in gene expression can easily impair function, yet can be undetectable by measuring averages
Sequencing data from bulk DNA or RNA from multiple cells provide global information on average states of cell populations. But with whole-genome amplification and NGS, researchers can detect variation in individual cancer cells and dissect tumor evolution. Such cancer genome sequencing will improve oncology by detecting rare tumor cells early, measuring intra-/intertumor heterogeneity, guiding chemotherapy and controlling drug resistance. The Single-Cell Sequencing conference explores the latest strategies, data analyses and clinical considerations that influence and aid cancer diagnosis, prognosis and prediction and will lead to individualized cancer therapy.
Sessions include presentations spanning the opportunities of clinical single-cell analysis from:
Sunney Xie, Ph.D., Mallinckrodt Professor. Chemistry and Chemical Biology, Harvard University
Maximilian Diehn, M.D., Ph.D., Assistant Professor, Radiation Oncology, Stanford Cancer Institute, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University
Denis Smirnov, Associate Scientific Director, US Biomarker Oncology, Janssen R&D US
James Hicks, Ph.D., Research Professor, Cancer Genomics, Cold Spring Harbor Laboratory
Jan Vijg, Ph.D., Professor and Chairman, Genetics, Albert Einstein College of Medicine
John F. Zhong, Ph.D., Associate Professor, Pathology, University of Southern California School of Medicine
Mark Hills, Ph.D., Research Scientist, Peter M. Lansdorp Laboratory, BC Cancer Research Centre
Michael Masterman-Smith, Ph.D., Entrepreneurial Scientist, UCLA California NanoSystems Institute
Parveen Kumar, Research Scientist, Thierry Voet Laboratory, Human Genetics, University of Leuven
Peter Nemes, Ph.D., Assistant Professor, Chemistry, George Washington University
Theresa Zhang, Ph.D., Vice President, Research Services, Personal Genome Diagnostics
Yong Wang, Ph.D., Senior Postdoctoral Fellow, Nicholas E. Navin Laboratory, Genetics, Bioinformatics, MD Anderson Cancer Center
Zivana Tezak, Ph.D., Associate Director, Science and Technology, Personalized Medicine, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), Center for Devices and Radiological Health (CDRH), FDA
Recommended Pre-Conference Courses
NGS Data Analysis – Determining Clinical Utility of Genome Variants Monday, August 18 | 9:00am – 12:00pm This course will explore the strategies of genomic data analysis and interpretation, an emergent discipline that seeks to deliver better answers from NGS data so that patients and their physicians can determine informed healthcare decisions. View Details
NGS as a Diagnostics Platform Monday, August 18 | 2:00pm – 5:00pm The focus of this short course will be on understanding the use of NGS in clinical diagnosis, practical implementation of NGS in clinical laboratories and analysis of large data sets by using bioinformatics tools to parse and interpret data in relation to the clinical phenotype. The concluding presentation will be dedicated to quality and standardization of NGS assays. View Details
Prediction of the Winner RNA Technology, the FRONTIER of SCIENCE on RNA Biology, Cancer and Therapeutics & The Start Up Landscape in Boston
Curator: Aviva Lev-Ari, PhD, RN
Article 21.1.4- Prediction of the Winner RNA Technology, the FRONTIER of SCIENCE on RNA Biology, Cancer and Therapeutics & The Start Up Landscape in BostonGene Editing – New Technology The Missing link for Gene Therapy
The FRONTIER of SCIENCE on RNA Biology, Cancer and Therapeutic Implications was presented in Lecture Contents delivered at
Koch Institute for Integrative Cancer Research, Summer Symposium 2014 @MIT, 6/13/2014.
REVIEW the LECTURES
Lecture Contents delivered at Koch Institute for Integrative Cancer Research, Summer Symposium 2014: RNA Biology, Cancer and Therapeutic Implications, June 13, 2014 @MIT
Dicerna Therapeutics Inc. — a company developing drugs using a gene-silencing technology called RNA interference — became the first Massachusetts biotech to go public this year. Its shares surged a stunning 207 percent on the first day of trading.
Companies are deploying a range of technologies in the complex realm of RNA drugs. But the goal of all of them is to
battle diseases such as cancer and rare genetic disorders by turning on and off the genes that regulate proteins in people’s cells.
Cambridge-based Alnylam Pharmaceuticals Inc. and
Moderna Therapeutics Inc. — has generated new optimism about bringing RNA therapies to the market.
At the J.P. Morgan Healthcare Conference in San Francisco last month, several firms drew attention by disclosing investments and positive data from clinical trials. One study by
Sarepta Therapeutics Inc. of Cambridge found its experimental RNA drug to treat a form of muscular dystrophy in young boys helped them retain their ability to walk.
“You can see all of the RNA stocks trending up,” said Bruce Booth, partner in the life sciences group at Atlas Venture, a Cambridge venture capital firm that has invested in RNA start-ups. “We’re finally seeing the signal that RNA can open up new therapeutic pathways.”
The successful initial public offering of Dicerna, whose technology blocks disease-causing overproduction of protein in cells, shows investor appetite for RNA drug companies is high. A decade after the mapping of the human genome, scientists are finally gaining the “molecular understanding” to produce “precision medicines,” said Christoph Westphal, a partner in the Boston venture firm Longwood Fund, which has bankrolled RNA research.
Alnylam Deal: Genzyme took a 12 percent stake in Alnylam and won the rights to eventually market several of its drugs being developed to treat rare blood disorders such as hemophilia and porphyria.
Alnylam separately said it was plunking down $175 million in cash and stock to acquire San Francisco biotech Sirna Therapeutics Inc. and its pipeline of RNA drug candidates from pharmaceutical giant Merck & Co.
Venture-backed Moderna also joined in by pocketing a $125 million investment from Alexion Pharmaceuticals Inc. of Cheshire, Conn., to deploy a different technology, messenger RNA, which seeks to battle rare diseases by stimulating protein growth.
Moderna promptly spun out its cancer-fighting messenger RNA research program into a separate company, Onkaido Therapeutics, which will work on 15 experimental drugs.
Onkaido will start out wholly owned by Moderna, but Moderna may soon seek to partner with other investors or larger drug makers to speed its progress.
Chief executive Stephane Bancel said Moderna is creating a technology “platform,” akin to an operating system, that can help multiple business partners develop medicines. The partners include Anglo-Swedish drug maker AstraZeneca plc, with which Moderna has a collaboration on RNA drugs to fight cardiovascular, metabolic, and kidney disorders.
Bancel and others in the field say RNA therapeutics offer advantages over traditional small molecule drugs or biotech medicines grown from organic materials.
“We can do hundreds, if not thousands, of drugs the biotechnology industry can’t do, by injecting messenger RNA into cells,” Bancel said. The messenger RNA contains instructions telling cells how to make protein and whether to leave it in the cell or carry it into the bloodstream. As for companies working in RNAi research, such as Alnylam, he said, “We see them as collaborators. We’re doing the opposite of one another, but we’re working in the same field.”
Another local company, Atlas-funded RaNA Therapeutics Inc. of Cambridge, is working on a technology called long non-coding RNA to create a class of targeted medicines that can selectively activate protein in cells.
Even the largest Massachusetts biotech, Cambridge-based Biogen Idec Inc., secured a foothold in the emerging RNA space last year by striking a partnership with Isis Pharmaceuticals Inc. of Carlsbad, Calif., which is pioneering yet another RNA technology, called antisense, to combat neurological disorders.
“RNA is hot,” said Chris Garabedian, chief executive of Sarepta, which also works on antisense technology, using “splice switching” to move a gene’s coding around and let it regulate protein levels. “We are hitting the RNA space at a unique time. Several companies over the past year and a half have started to turn the corner with some very compelling [clinical] data.” Garabedian moved the company to Cambridge from Bothell, Wash., outside Seattle, two years ago because he concluded it would be easier to attract RNA research talent in the Boston area. Sarepta is building a new lab near Kendall Square. He, too, sees the small cluster of RNA drug companies in the area less as rivals than as partners in an emerging field. “We can play in anybody’s sandbox,” he said.
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