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Archive for the ‘Artificial Intelligence – General’ Category


Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

The term ‘antibiotic’ was introduced by Selman Waksman as any small molecule, produced by a microbe, with antagonistic properties on the growth of other microbes. An antibiotic interferes with bacterial survival via a specific mode of action but more importantly, at therapeutic concentrations, it is sufficiently potent to be effective against infection and simultaneously presents minimal toxicity. Infectious diseases have been a challenge throughout the ages. From 1347 to 1350, approximately one-third of Europe’s population perished to Bubonic plague. Advances in sanitary and hygienic conditions sufficed to control further plague outbreaks. However, these persisted as a recurrent public health issue. Likewise, infectious diseases in general remained the leading cause of death up to the early 1900s. The mortality rate shrunk after the commercialization of antibiotics, which given their impact on the fate of mankind, were regarded as a ‘medical miracle’. Moreover, the non-therapeutic application of antibiotics has also greatly affected humanity, for instance those used as livestock growth promoters to increase food production after World War II.

 

Currently, more than 2 million North Americans acquire infections associated with antibiotic resistance every year, resulting in 23,000 deaths. In Europe, nearly 700 thousand cases of antibiotic-resistant infections directly develop into over 33,000 deaths yearly, with an estimated cost over €1.5 billion. Despite a 36% increase in human use of antibiotics from 2000 to 2010, approximately 20% of deaths worldwide are related to infectious diseases today. Future perspectives are no brighter, for instance, a government commissioned study in the United Kingdom estimated 10 million deaths per year from antibiotic resistant infections by 2050.

 

The increase in antibiotic-resistant bacteria, alongside the alarmingly low rate of newly approved antibiotics for clinical usage, we are on the verge of not having effective treatments for many common infectious diseases. Historically, antibiotic discovery has been crucial in outpacing resistance and success is closely related to systematic procedures – platforms – that have catalyzed the antibiotic golden age, namely the Waksman platform, followed by the platforms of semi-synthesis and fully synthetic antibiotics. Said platforms resulted in the major antibiotic classes: aminoglycosides, amphenicols, ansamycins, beta-lactams, lipopeptides, diaminopyrimidines, fosfomycins, imidazoles, macrolides, oxazolidinones, streptogramins, polymyxins, sulphonamides, glycopeptides, quinolones and tetracyclines.

 

The increase in drug-resistant pathogens is a consequence of multiple factors, including but not limited to high rates of antimicrobial prescriptions, antibiotic mismanagement in the form of self-medication or interruption of therapy, and large-scale antibiotic use as growth promotors in livestock farming. For example, 60% of the antibiotics sold to the USA food industry are also used as therapeutics in humans. To further complicate matters, it is estimated that $200 million is required for a molecule to reach commercialization, with the risk of antimicrobial resistance rapidly developing, crippling its clinical application, or on the opposing end, a new antibiotic might be so effective it is only used as a last resort therapeutic, thus not widely commercialized.

 

Besides a more efficient management of antibiotic use, there is a pressing need for new platforms capable of consistently and efficiently delivering new lead substances, which should attend their precursors impressively low rates of success, in today’s increasing drug resistance scenario. Antibiotic Discovery Platforms are aiming to screen large libraries, for instance the reservoir of untapped natural products, which is likely the next antibiotic ‘gold mine’. There is a void between phenotanypic screening (high-throughput) and omics-centered assays (high-information), where some mechanistic and molecular information complements antimicrobial activity, without the laborious and extensive application of various omics assays. The increasing need for antibiotics drives the relentless and continuous research on the foreground of antibiotic discovery. This is likely to expand our knowledge on the biological events underlying infectious diseases and, hopefully, result in better therapeutics that can swing the war on infectious diseases back in our favor.

 

During the genomics era came the target-based platform, mostly considered a failure due to limitations in translating drugs to the clinic. Therefore, cell-based platforms were re-instituted, and are still of the utmost importance in the fight against infectious diseases. Although the antibiotic pipeline is still lackluster, especially of new classes and novel mechanisms of action, in the post-genomic era, there is an increasingly large set of information available on microbial metabolism. The translation of such knowledge into novel platforms will hopefully result in the discovery of new and better therapeutics, which can sway the war on infectious diseases back in our favor.

 

References:

 

https://www.mdpi.com/2079-6382/8/2/45/htm

 

https://www.ncbi.nlm.nih.gov/pubmed/19515346

 

https://www.ajicjournal.org/article/S0196-6553(11)00184-2/fulltext

 

https://www.ncbi.nlm.nih.gov/pubmed/21700626

 

http://www.med.or.jp/english/journal/pdf/2009_02/103_108.pdf

 

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BioInformatic Resources at the Environmental Protection Agency: Tools and Webinars on Toxicity Prediction

Curator Stephen J. Williams Ph.D.

New GenRA Module in EPA’s CompTox Dashboard Will Help Predict Potential Chemical Toxicity

Published September 25, 2018

As part of its ongoing computational toxicology research, EPA is developing faster and improved approaches to evaluate chemicals for potential health effects.  One commonly applied approach is known as chemical read-across. Read-across uses information about how a chemical with known data behaves to make a prediction about the behavior of another chemical that is “similar” but does not have as much data. Current read-across, while cost-effective, relies on a subjective assessment, which leads to varying predictions and justifications depending on who undertakes and evaluates the assessment.

To reduce uncertainties and develop a more objective approach, EPA researchers have developed an automated read-across tool called Generalized Read-Across (GenRA), and added it to the newest version of the EPA Computational Toxicology Dashboard. The goal of GenRA is to encode as many expert considerations used within current read-across approaches as possible and combine these with data-driven approaches to transition read-across towards a more systematic and data-based method of making predictions.

EPA chemist Dr. Grace Patlewicz says it was this uncertainty that motivated the development of GenRA. “You don’t actually know if you’ve been successful at using read-across to help predict chemical toxicity because it’s a judgement call based on one person versus the next. That subjectivity is something we were trying to move away from.” Patlewicz says.

Since toxicologists and risk assessors are already familiar with read-across, EPA researchers saw value in creating a tool that that was aligned with the current read-across workflow but which addressed uncertainty using data analysis methods in what they call a “harmonized-hybrid workflow.”

In its current form, GenRA lets users find analogues, or chemicals that are similar to their target chemical, based on chemical structural similarity. The user can then select which analogues they want to carry forward into the GenRA prediction by exploring the consistency and concordance of the underlying experimental data for those analogues. Next, the tool predicts toxicity effects of specific repeated dose studies. Then, a plot with these outcomes is generated based on a similarity-weighted activity of the analogue chemicals the user selected. Finally, the user is presented with a data matrix view showing whether a chemical is predicted to be toxic (yes or no) for a chosen set of toxicity endpoints, with a quantitative measure of uncertainty.

The team is also comparing chemicals based on other similarity contexts, such as physicochemical characteristics or metabolic similarity, as well as extending the approach to make quantitative predictions of toxicity.

Patlewicz thinks incorporating other contexts and similarity measures will refine GenRA to make better toxicity predictions, fulfilling the goal of creating a read-across method capable of assessing thousands of chemicals that currently lack toxicity data.

“That’s the direction that we’re going in,” Patlewicz says. “Recognizing where we are and trying to move towards something a little bit more objective, showing how aspects of the current read-across workflow could be refined.”

Learn more at: https://comptox.epa.gov

 

A listing of EPA Tools for Air Quality Assessment

Tools

  • Atmospheric Model Evaluation Tool (AMET)
    AMET helps in the evaluation of meteorological and air quality simulations.
  • Benchmark Dose Software (BMDS)
    EPA developed the Benchmark Dose Software (BMDS) as a tool to help estimate dose or exposure of a chemical or chemical mixture associated with a given response level. The methodology is used by EPA risk assessors and is fast becoming the world’s standard for dose-response analysis for risk assessments, including air pollution risk assessments.
  • BenMAP
    BenMAP is a Windows-based computer program that uses a Geographic Information System (GIS)-based to estimate the health impacts and economic benefits occurring when populations experience changes in air quality.
  • Community-Focused Exposure and Risk Screening Tool (C-FERST)
    C-FERST is an online tool developed by EPA in collaboration with stakeholders to provide access to resources that can be used with communities to help identify and learn more about their environmental health issues and explore exposure and risk reduction options.
  • Community Health Vulnerability Index
    EPA scientists developed a Community Health Vulnerability Index that can be used to help identify communities at higher health risk from wildfire smoke. Breathing smoke from a nearby wildfire is a health threat, especially for people with lung or heart disease, diabetes and high blood pressure as well as older adults, and those living in communities with poverty, unemployment and other indicators of social stress. Health officials can use the tool, in combination with air quality models, to focus public health strategies on vulnerable populations living in areas where air quality is impaired, either by wildfire smoke or other sources of pollution. The work was published in Environmental Science & Technology.
  • Critical Loads Mapper Tool
    The Critical Loads Mapper Tool can be used to help protect terrestrial and aquatic ecosystems from atmospheric deposition of nitrogen and sulfur, two pollutants emitted from fossil fuel burning and agricultural emissions. The interactive tool provides easy access to information on deposition levels through time; critical loads, which identify thresholds when pollutants have reached harmful levels; and exceedances of these thresholds.
  • EnviroAtlas
    EnviroAtlas provides interactive tools and resources for exploring the benefits people receive from nature or “ecosystem goods and services”. Ecosystem goods and services are critically important to human health and well-being, but they are often overlooked due to lack of information. Using EnviroAtlas, many types of users can access, view, and analyze diverse information to better understand the potential impacts of various decisions.
  • EPA Air Sensor Toolbox for Citizen Scientists
    EPA’s Air Sensor Toolbox for Citizen Scientists provides information and guidance on new low-cost compact technologies for measuring air quality. Citizens are interested in learning more about local air quality where they live, work and play. EPA’s Toolbox includes information about: Sampling methodologies; Calibration and validation approaches; Measurement methods options; Data interpretation guidelines; Education and outreach; and Low cost sensor performance information.
  • ExpoFIRST
    The Exposure Factors Interactive Resource for Scenarios Tool (ExpoFIRST) brings data from EPA’s Exposure Factors Handbook: 2011 Edition (EFH) to an interactive tool that maximizes flexibility and transparency for exposure assessors. ExpoFIRST represents a significant advance for regional, state, and local scientists in performing and documenting calculations for community and site-specific exposure assessments, including air pollution exposure assessments.
  • EXPOsure toolbox (ExpoBox)
    This is a toolbox created to assist individuals from within government, industry, academia, and the general public with assessing exposure, including exposure to air contaminants, fate and transport processes of air pollutants and their potential exposure concentrations. It is a compendium of exposure assessment tools that links to guidance documents, databases, models, reference materials, and other related resources.
  • Federal Reference & Federal Equivalency Methods
    EPA scientists develop and evaluate Federal Reference Methods and Federal Equivalency Methods for accurately and reliably measuring six primary air pollutants in outdoor air. These methods are used by states and other organizations to assess implementation actions needed to attain National Ambient Air Quality Standards.
  • Fertilizer Emission Scenario Tool for CMAQ (FEST-C)
    FEST-C facilitates the definition and simulation of new cropland farm management system scenarios or editing of existing scenarios to drive Environmental Policy Integrated Climate model (EPIC) simulations.  For the standard 12km continental Community Multi-Scale Air Quality model (CMAQ) domain, this amounts to about 250,000 simulations for the U.S. alone. It also produces gridded daily EPIC weather input files from existing hourly Meteorology-Chemistry Interface Processor (MCIP) files, transforms EPIC output files to CMAQ-ready input files and links directly to Visual Environment for Rich Data Interpretation (VERDI) for spatial visualization of input and output files. The December 2012 release will perform all these functions for any CMAQ grid scale or domain.
  • Instruction Guide and Macro Analysis Tool for Community-led Air Monitoring 
    EPA has developed two tools for evaluating the performance of low-cost sensors and interpreting the data they collect to help citizen scientists, communities, and professionals learn about local air quality.
  • Integrated Climate and Land use Scenarios (ICLUS)
    Climate change and land-use change are global drivers of environmental change. Impact assessments frequently show that interactions between climate and land-use changes can create serious challenges for aquatic ecosystems, water quality, and air quality. Population projections to 2100 were used to model the distribution of new housing across the landscape. In addition, housing density was used to estimate changes in impervious surface cover.  A final report, datasets, the ICLUS+ Web Viewer and ArcGIS tools are available.
  • Indoor Semi-Volatile Organic Compound (i-SVOC)
    i-SVOC Version 1.0 is a general-purpose software application for dynamic modeling of the emission, transport, sorption, and distribution of semi-volatile organic compounds (SVOCs) in indoor environments. i-SVOC supports a variety of uses, including exposure assessment and the evaluation of mitigation options. SVOCs are a diverse group of organic chemicals that can be found in: Many are also present in indoor air, where they tend to bind to interior surfaces and particulate matter (dust).

    • Pesticides;
    • Ingredients in cleaning agents and personal care products;
    • Additives to vinyl flooring, furniture, clothing, cookware, food packaging, and electronics.
  • Municipal Solid Waste Decision Support Tool (MSW DST)EXIT
    This tool is designed to aid solid waste planners in evaluating the cost and environmental aspects of integrated municipal solid waste management strategies. The tool is the result of collaboration between EPA and RTI International and its partners.
  • Optical Noise-Reduction Averaging (ONA) Program Improves Black Carbon Particle Measurements Using Aethalometers
    ONA is a program that reduces noise in real-time black carbon data obtained using Aethalometers. Aethalometers optically measure the concentration of light absorbing or “black” particles that accumulate on a filter as air flows through it. These particles are produced by incomplete fossil fuel, biofuel and biomass combustion. Under polluted conditions, they appear as smoke or haze.
  • RETIGO tool
    Real Time Geospatial Data Viewer (RETIGO) is a free, web-based tool that shows air quality data that are collected while in motion (walking, biking or in a vehicle). The tool helps users overcome technical barriers to exploring air quality data. After collecting measurements, citizen scientists and other users can import their own data and explore the data on a map.
  • Remote Sensing Information Gateway (RSIG)
    RSIG offers a new way for users to get the multi-terabyte, environmental datasets they want via an interactive, Web browser-based application. A file download and parsing process that now takes months will be reduced via RSIG to minutes.
  • Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure (IAQX)
    IAQX version 1.1 is an indoor air quality (IAQ) simulation software package that complements and supplements existing indoor air quality simulation (IAQ) programs. IAQX is for advanced users who have experience with exposure estimation, pollution control, risk assessment, and risk management. There are many sources of indoor air pollution, such as building materials, furnishings, and chemical cleaners. Since most people spend a large portion of their time indoors, it is important to be able to estimate exposure to these pollutants. IAQX helps users analyze the impact of pollutant sources and sinks, ventilation, and air cleaners. It performs conventional IAQ simulations to calculate the pollutant concentration and/or personal exposure as a function of time. It can also estimate adequate ventilation rates based on user-provided air quality criteria. This is a unique feature useful for product stewardship and risk management.
  • Spatial Allocator
    The Spatial Allocator provides tools that could be used by the air quality modeling community to perform commonly needed spatial tasks without requiring the use of a commercial Geographic Information System (GIS).
  • Traceability Protocol for Assay and Certification of Gaseous Calibration Standards
    This is used to certify calibration gases for ambient and continuous emission monitors. It specifies methods for assaying gases and establishing traceability to National Institute of Standards and Technology (NIST) reference standards. Traceability is required under EPA ambient and continuous emission monitoring regulations.
  • Watershed Deposition Mapping Tool (WDT)
    WDT provides an easy to use tool for mapping the deposition estimates from CMAQ to watersheds to provide the linkage of air and water needed for TMDL (Total Maximum Daily Load) and related nonpoint-source watershed analyses.
  • Visual Environment for Rich Data Interpretation (VERDI)
    VERDI is a flexible, modular, Java-based program for visualizing multivariate gridded meteorology, emissions, and air quality modeling data created by environmental modeling systems such as CMAQ and the Weather Research and Forecasting (WRF) model.

 

Databases

  • Air Quality Data for the CDC National Environmental Public Health Tracking Network 
    EPA’s Exposure Research scientists are collaborating with the Centers for Disease Control and Prevention (CDC) on a CDC initiative to build a National Environmental Public Health Tracking (EPHT) network. Working with state, local and federal air pollution and health agencies, the EPHT program is facilitating the collection, integration, analysis, interpretation, and dissemination of data from environmental hazard monitoring, and from human exposure and health effects surveillance. These data provide scientific information to develop surveillance indicators, and to investigate possible relationships between environmental exposures, chronic disease, and other diseases, that can lead to interventions to reduce the burden of theses illnesses. An important part of the initiative is air quality modeling estimates and air quality monitoring data, combined through Bayesian modeling that can be linked with health outcome data.
  • EPAUS9R – An Energy Systems Database for use with the Market Allocation (MARKAL) Model
    The EPAUS9r is a regional database representation of the United States energy system. The database uses the MARKAL model. MARKAL is an energy system optimization model used by local and federal governments, national and international communities and academia. EPAUS9r represents energy supply, technology, and demand throughout the major sectors of the U.S. energy system.
  • Fused Air Quality Surfaces Using Downscaling
    This database provides access to the most recent O3 and PM2.5 surfaces datasets using downscaling.
  • Health & Environmental Research Online (HERO)
    HERO provides access to scientific literature used to support EPA’s integrated science assessments, including the  Integrated Science Assessments (ISA) that feed into the National Ambient Air Quality (NAAQS) reviews.
  • SPECIATE 4.5 Database
    SPECIATE is a repository of volatile organic gas and particulate matter (PM) speciation profiles of air pollution sources.

A listing of EPA Tools and Databases for Water Contaminant Exposure Assessment

Exposure and Toxicity

  • EPA ExpoBox (A Toolbox for Exposure Assessors)
    This toolbox assists individuals from within government, industry, academia, and the general public with assessing exposure from multiple media, including water and sediment. It is a compendium of exposure assessment tools that links to guidance documents, databases, models, reference materials, and other related resources.

Chemical and Product Categories (CPCat) Database
CPCat is a database containing information mapping more than 43,000 chemicals to a set of terms categorizing their usage or function. The comprehensive list of chemicals with associated categories of chemical and product use was compiled from publically available sources. Unique use category taxonomies from each source are mapped onto a single common set of approximately 800 terms. Users can search for chemicals by chemical name, Chemical Abstracts Registry Number, or by CPCat terms associated with chemicals.

A listing of EPA Tools and Databases for Chemical Toxicity Prediction & Assessment

  • Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS)
    SeqAPASS is a fast, online screening tool that allows researchers and regulators to extrapolate toxicity information across species. For some species, such as humans, mice, rats, and zebrafish, the EPA has a large amount of data regarding their toxicological susceptibility to various chemicals. However, the toxicity data for numerous other plants and animals is very limited. SeqAPASS extrapolates from these data rich model organisms to thousands of other non-target species to evaluate their specific potential chemical susceptibility.

 

A listing of EPA Webinar and Literature on Bioinformatic Tools and Projects

Comparative Bioinformatics Applications for Developmental Toxicology

Discuss how the US EPA/NCCT is trying to solve the problem of too many chemicals, too high cost, and too much biological uncertainty Discuss the solution the ToxCast Program is proposing; a data-rich system to screen, classify and rank chemicals for further evaluation

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dirEntryId=186844

CHEMOINFORMATIC AND BIOINFORMATIC CHALLENGES AT THE US ENVIRONMENTAL PROTECTION AGENCY.

This presentation will provide an overview of both the scientific program and the regulatory activities related to computational toxicology. This presentation will provide an overview of both the scientific program and the regulatory activities related to computational toxicology.

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dirEntryId=154013

How Can We Use Bioinformatics to Predict Which Agents Will Cause Birth Defects?

The availability of genomic sequences from a growing number of human and model organisms has provided an explosion of data, information, and knowledge regarding biological systems and disease processes. High-throughput technologies such as DNA and protein microarray biochips are now standard tools for probing the cellular state and determining important cellular behaviors at the genomic/proteomic levels. While these newer technologies are beginning to provide important information on cellular reactions to toxicant exposure (toxicogenomics), a major challenge that remains is the formulation of a strategy to integrate transcript, protein, metabolite, and toxicity data. This integration will require new concepts and tools in bioinformatics. The U.S. National Library of Medicine’s Pubmed site includes 19 million citations and abstracts and continues to grow. The BDSM team is now working on assembling the literature’s unstructured data into a structured database and linking it to BDSM within a system that can then be used for testing and generating new hypotheses. This effort will generate data bases of entities (such as genes, proteins, metabolites, gene ontology processes) linked to PubMed identifiers/abstracts and providing information on the relationships between them. The end result will be an online/standalone tool that will help researchers to focus on the papers most relevant to their query and uncover hidden connections and obvious information gaps.

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dirEntryId=227345

ADVANCED PROTEOMICS AND BIOINFORMATICS TOOLS IN TOXICOLOGY RESEARCH: OVERCOMING CHALLENGES TO PROVIDE SIGNIFICANT RESULTS

This presentation specifically addresses the advantages and limitations of state of the art gel, protein arrays and peptide-based labeling proteomic approaches to assess the effects of a suite of model T4 inhibitors on the thyroid axis of Xenopus laevis.

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NHEERL&dirEntryId=152823

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dirEntryId=344452

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dateBeginPublishedPresented=03%2F26%2F2014&dateEndPublishedPresented=03%2F26%2F2019&dirEntryId=344452&keyword=Chemical+Safety&showCriteria=2&sortBy=pubDateYear&subject=Chemical+Safety+Research

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dateBeginPublishedPresented=04%2F02%2F2014&dateEndPublishedPresented=04%2F02%2F2019&dirEntryId=344452&keyword=Chemical+Safety&showCriteria=2&sortBy=pubDateYear&subject=Chemical+Safety+Research

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dateBeginPublishedPresented=04%2F02%2F2014&dateEndPublishedPresented=04%2F02%2F2019&dirEntryId=344452&fed_org_id=111&keyword=Chemical+Safety&showCriteria=2&sortBy=pubDateYear&subject=Chemical+Safety+Research

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dirEntryId=344452&fed_org_id=111&keyword=Chemical+Safety&showCriteria=2&sortBy=pubDateYear&subject=Chemical+Safety+Research

 

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dateBeginPublishedPresented=03%2F26%2F2014&dateEndPublishedPresented=03%2F26%2F2019&dirEntryId=344452&fed_org_id=111&keyword=Chemical+Safety&showCriteria=2&sortBy=pubDateYear&subject=Chemical+Safety+Research

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dirEntryId=344452&fed_org_id=111&keyword=Chemical+Safety&showCriteria=2&sortBy=pubDateYear&subject=Chemical+Safety+Research

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dateBeginPublishedPresented=04%2F11%2F2014&dateEndPublishedPresented=04%2F11%2F2019&dirEntryId=344452&fed_org_id=111&keyword=Chemical+Safety&showCriteria=2&sortBy=pubDateYear&subject=Chemical+Safety+Research

Bioinformatic Integration of in vivo Data and Literature-based Gene Associations for Prioritization of Adverse Outcome Pathway Development

Adverse outcome pathways (AOPs) describe a sequence of events, beginning with a molecular initiating event (MIE), proceeding via key events (KEs), and culminating in an adverse outcome (AO). A challenge for use of AOPs in a safety evaluation context has been identification of MIEs and KEs relevant for AOs observed in regulatory toxicity studies. In this work, we implemented a bioinformatic approach that leverages mechanistic information in the literature and the AOs measured in regulatory toxicity studies to prioritize putative MIEs and/or early KEs for AOP development relevant to chemical safety evaluation. The US Environmental Protection Agency Toxicity Reference Database (ToxRefDB, v2.0) contains effect information for >1000 chemicals curated from >5000 studies or summaries from sources including data evaluation records from the US EPA Office of Pesticide Programs, the National Toxicology Program (NTP), peer-reviewed literature, and pharmaceutical preclinical studies. To increase ToxRefDB interoperability, endpoint and effect information were cross-referenced with codes from the United Medical Language System, which enabled mapping of in vivo pathological effects from ToxRefDB to PubMed (via Medical Subject Headings or MeSH). This enabled linkage to any resource that is also connected to PubMed or indexed with MeSH. A publicly available bioinformatic tool, the Entity-MeSH Co-occurrence Network (EMCON), uses multiple data sources and a measure of mutual information to identify genes most related to a MeSH term. Using EMCON, gene sets were generated for endpoints of toxicological relevance in ToxRefDB linking putative KEs and/or MIEs. The Comparative Toxicogenomics Database was used to further filter important associations. As a proof of concept, thyroid-related effects and their highly associated genes were examined, and demonstrated relevant MIEs and early KEs for AOPs to describe thyroid-related AOs. The ToxRefDB to gene mapping for thyroid resulted in >50 unique gene to chemical relationships. Integrated use of EMCON and ToxRefDB data provides a basis for rapid and robust putative AOP development, as well as a novel means to generate mechanistic hypotheses for specific chemicals. This abstract does not necessarily reflect U.S. EPA policy. Abstract and Poster for 2019 Society of Toxicology annual meeting in March 2019

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dateBeginPublishedPresented=04%2F11%2F2014&dateEndPublishedPresented=04%2F11%2F2019&dirEntryId=344452&keyword=Chemical+Safety&showCriteria=2&sortBy=pubDateYear&subject=Chemical+Safety+Research

A Web-Hosted R Workflow to Simplify and Automate the Analysis of 16S NGS Data

Next-Generation Sequencing (NGS) produces large data sets that include tens-of-thousands of sequence reads per sample. For analysis of bacterial diversity, 16S NGS sequences are typically analyzed in a workflow that containing best-of-breed bioinformatics packages that may leverage multiple programming languages (e.g., Python, R, Java, etc.). The process totransform raw NGS data to usable operational taxonomic units (OTUs) can be tedious due tothe number of quality control (QC) steps used in QIIME and other software packages forsample processing. Therefore, the purpose of this work was to simplify the analysis of 16SNGS data from a large number of samples by integrating QC, demultiplexing, and QIIME(Quantitative Insights Into Microbial Ecology) analysis in an accessible R project. User command line operations for each of the pipeline steps were automated into a workflow. In addition, the R server allows multi-user access to the automated pipeline via separate useraccounts while providing access to the same large set of underlying data. We demonstratethe applicability of this pipeline automation using 16S NGS data from approximately 100 stormwater runoff samples collected in a mixed-land use watershed in northeast Georgia. OTU tables were generated for each sample and the relative taxonomic abundances were compared for different periods over storm hydrographs to determine how the microbial ecology of a stream changes with rise and fall of stream stage. Our approach simplifies the pipeline analysis of multiple 16S NGS samples by automating multiple preprocessing, QC, analysis and post-processing command line steps that are called by a sequence of R scripts. Presented at ASM 2015 Rapid NGS Bioinformatic Pipelines for Enhanced Molecular Epidemiologic Investigation of Pathogens

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NERL&dirEntryId=309890

DEVELOPING COMPUTATIONAL TOOLS NECESSARY FOR APPLYING TOXICOGENOMICS TO RISK ASSESSMENT AND REGULATORY DECISION MAKING.

GENOMICS, PROTEOMICS & METABOLOMICS CAN PROVIDE USEFUL WEIGHT-OF-EVIDENCE DATA ALONG THE SOURCE-TO-OUTCOME CONTINUUM, WHEN APPROPRIATE BIOINFORMATIC AND COMPUTATIONAL METHODS ARE APPLIED TOWARDS INTEGRATING MOLECULAR, CHEMICAL AND TOXICOGICAL INFORMATION. GENOMICS, PROTEOMICS & METABOLOMICS CAN PROVIDE USEFUL WEIGHT-OF-EVIDENCE DATA ALONG THE SOURCE-TO-OUTCOME CONTINUUM, WHEN APPROPRIATE BIOINFORMATIC AND COMPUTATIONAL METHODS ARE APPLIED TOWARDS INTEGRATING MOLECULAR, CHEMICAL AND TOXICOGICAL INFORMATION.

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dirEntryId=156264

The Human Toxome Project

The Human Toxome project, funded as an NIH Transformative Research grant 2011–‐ 2016, is focused on developing the concepts and the means for deducing, validating, and sharing molecular Pathways of Toxicity (PoT). Using the test case of estrogenic endocrine disruption, the responses of MCF–‐7 human breast cancer cells are being phenotyped by transcriptomics and mass–‐spectroscopy–‐based metabolomics. The bioinformatics tools for PoT deduction represent a core deliverable. A number of challenges for quality and standardization of cell systems, omics technologies, and bioinformatics are being addressed. In parallel, concepts for annotation, validation, and sharing of PoT information, as well as their link to adverse outcomes, are being developed. A reasonably comprehensive public database of PoT, the Human Toxome Knowledge–‐base, could become a point of reference for toxicological research and regulatory tests strategies. A reasonably comprehensive public database of PoT, the Human Toxome Knowledge–‐base, could become a point of reference for toxicological research and regulatory tests strategies.

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCCT&dirEntryId=309453

High-Resolution Metabolomics for Environmental Chemical Surveillance and Bioeffect Monitoring

High-Resolution Metabolomics for Environmental Chemical Surveillance and Bioeffect Monitoring (Presented by: Dean Jones, PhD, Department of Medicine, Emory University) (2/28/2013)

https://www.epa.gov/chemical-research/high-resolution-metabolomics-environmental-chemical-surveillance-and-bioeffect

Identification of Absorption, Distribution, Metabolism, and Excretion (ADME) Genes Relevant to Steatosis Using a Gene Expression Approach

Absorption, distribution, metabolism, and excretion (ADME) impact chemical concentration and activation of molecular initiating events of Adverse Outcome Pathways (AOPs) in cellular, tissue, and organ level targets. In order to better describe ADME parameters and how they modulate potential hazards posed by chemical exposure, our goal is to investigate the relationship between AOPs and ADME related genes and functional information. Given the scope of this task, we began using hepatic steatosis as a case study. To identify ADME genes related to steatosis, we used the publicly available toxicogenomics database, Open TG-GATEsTM. This database contains standardized rodent chemical exposure data from 170 chemicals (mostly drugs), along with differential gene expression data and corresponding associated pathological changes. We examined the chemical exposure microarray data set gathered from 9 chemical exposure treatments resulting in pathologically confirmed (minimal, moderate and severe) incidences of hepatic steatosis. From this differential gene expression data set, we utilized differential expression analyses to identify gene changes resulting from the chemical exposures leading to hepatic steatosis. We then selected differentially expressed genes (DEGs) related to ADME by filtering all genes based on their ADME functional identities. These DEGs include enzymes such as cytochrome p450, UDP glucuronosyltransferase, flavin-containing monooxygenase and transporter genes such as solute carriers and ATP-binding cassette transporter families. The up and downregulated genes were identified across these treatments. Total of 61 genes were upregulated and 68 genes were down regulated in all treatments. Meanwhile, 25 genes were both up regulated and downregulated across all the treatments. This work highlights the application of bioinformatics in linking AOPs with gene modulations specifically in relationships to ADME and exposures to chemicals. This abstract does not necessarily reflect U.S. EPA policy. This work highlights the application of bioinformatics tools to identify genes that are modulated by adverse outcomes. Specifically, we delineate a method to identify genes that are related to ADME and can impact target tissue dose in response to chemical exposures. The computational method outlined in this work is applicable to any adverse outcome pathway, and provide a linkage between chemical exposure, target tissue dose, and adverse outcomes. Application of this method will allow for the rapid screening of chemicals for their impact on ADME-related genes using available gene data bases in literature.

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NHEERL&dirEntryId=341273

Development of Environmental Fate and Metabolic Simulators

Presented at Bioinformatics Open Source Conference (BOSC), Detroit, MI, June 23-24, 2005. see description

https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NERL&dirEntryId=257172

 

Useful Webinars on EPA Computational Tools and Informatics

 

Computational Toxicology Communities of Practice

Computational Toxicology Research

EPA’s Computational Toxicology Communities of Practice is composed of hundreds of stakeholders from over 50 public and private sector organizations (ranging from EPA, other federal agencies, industry, academic institutions, professional societies, nongovernmental organizations, environmental non-profit groups, state environmental agencies and more) who have an interest in using advances in computational toxicology and exposure science to evaluate the safety of chemicals.

The Communities of Practice is open to the public. Monthly webinars are held at EPA’s RTP campus, on the fourth Thursday of the month (occasionally rescheduled in November and December to accommodate holiday schedules), from 11am-Noon EST/EDT. Remote participation is available. For more information or to be added to the meeting email list, contact: Monica Linnenbrink (linnenbrink.monica@epa.gov).

Related Links

Past Webinar Presentations

Presentation File Presented By Date
OPEn structure-activity Relationship App (OPERA) Powerpoint(VideoEXIT) Dr. Kamel Mansouri, Lead Computational Chemist contractor for Integrated Laboratory Systems in the National Institute of Environmental Health Sciences 2019/4/25
CompTox Chemicals Dashboard and InVitroDB V3 (VideoEXIT) Dr. Antony Williams, Chemist in EPA’s National Center for Computational Toxicology and Dr. Katie Paul-Friedman, Toxicologist in EPA’s National Center for Computational Toxicology 2019/3/28
The Systematic Empirical Evaluation of Models (SEEM) framework (VideoEXIT) Dr. John Wambaugh, Physical Scientist in EPA’s National Center for Computational Toxicology 2019/2/28
ToxValDB: A comprehensive database of quantitative in vivo study results from over 25,000 chemicals (VideoEXIT) Dr. Richard Judson, Research Chemist in EPA’s National Center for Computational Toxicology 2018/12/20
Sequence Alignment to Predict Across Species Susceptibility (seqAPASS) (VideoEXIT) Dr. Carlie LaLone, Bioinformaticist, EPA’s National Health and Environmental Effects Research Laboratory 2018/11/29
Chemicals and Products Database (VideoEXIT) Dr. Kathie Dionisio, Environmental Health Scientist, EPA’s National Exposure Research Laboratory 2018/10/25
CompTox Chemicals Dashboard V3 (VideoEXIT) Dr. Antony Williams, Chemist, EPA National Center for Computational Toxicology (NCCT). 2018/09/27
Generalised Read-Across (GenRA) (VideoEXIT) Dr. Grace Patlewicz, Chemist, EPA National Center for Computational Toxicology (NCCT). 2018/08/23
EPA’S ToxCast Owner’s Manual  (VideoEXIT) Monica Linnenbrink, Strategic Outreach and Communication lead, EPA National Center for Computational Toxicology (NCCT). 2018/07/26
EPA’s Non-Targeted Analysis Collaborative Trial (ENTACT)      (VideoEXIT) Elin Ulrich, Research Chemist in the Public Health Chemistry Branch, EPA National Exposure Research Laboratory (NERL). 2018/06/28
ECOTOX Knowledgebase: New Tools and Data Visualizations(VideoEXIT) Colleen Elonen, Translational Toxicology Branch, and Dr. Jennifer Olker, Systems Toxicology Branch, in the Mid-Continent Ecology Division of EPA’s National Health & Environmental Effects Research Laboratory (NHEERL) 2018/05/24
Investigating Chemical-Microbiota Interactions in Zebrafish (VideoEXIT) Tamara Tal, Biologist in the Systems Biology Branch, Integrated Systems Toxicology Division, EPA’s National Health & Environmental Effects Research Laboratory (NHEERL) 2018/04/26
The CompTox Chemistry Dashboard v2.6: Delivering Improved Access to Data and Real Time Predictions (VideoEXIT) Tony Williams, Computational Chemist, EPA’s National Center for Computational Toxicology (NCCT) 2018/03/29
mRNA Transfection Retrofits Cell-Based Assays with Xenobiotic Metabolism (VideoEXIT* Audio starts at 10:17) Steve Simmons, Research Toxicologist, EPA’s National Center for Computational Toxicology (NCCT) 2018/02/22
Development and Distribution of ToxCast and Tox21 High-Throughput Chemical Screening Assay Method Description(VideoEXIT) Stacie Flood, National Student Services Contractor, EPA’s National Center for Computational Toxicology (NCCT) 2018/01/25
High-throughput H295R steroidogenesis assay: utility as an alternative and a statistical approach to characterize effects on steroidogenesis (VideoEXIT) Derik Haggard, ORISE Postdoctoral Fellow, EPA’s National Center for Computational Toxicology (NCCT) 2017/12/14
Systematic Review for Chemical Assessments: Core Elements and Considerations for Rapid Response (VideoEXIT) Kris Thayer, Director, Integrated Risk Information System (IRIS) Division of EPA’s National Center for Environmental Assessment (NCEA) 2017/11/16
High Throughput Transcriptomics (HTTr) Concentration-Response Screening in MCF7 Cells (VideoEXIT) Joshua Harrill, Toxicologist, EPA’s National Center for Computational Toxicology (NCCT) 2017/10/26
Learning Boolean Networks from ToxCast High-Content Imaging Data Todor Antonijevic, ORISE Postdoc, EPA’s National Center for Computational Toxicology (NCCT) 2017/09/28
Suspect Screening of Chemicals in Consumer Products Katherine Phillips, Research Chemist, Human Exposure and Dose Modeling Branch, Computational Exposure Division, EPA’s National Exposure Research Laboratory (NERHL) 2017/08/31
The EPA CompTox Chemistry Dashboard: A Centralized Hub for Integrating Data for the Environmental Sciences (VideoEXIT) Antony Williams, Chemist, EPA’s National Center for Computational Toxicology (NCCT) 2017/07/27
Navigating Through the Minefield of Read-Across Tools and Frameworks: An Update on Generalized Read-Across (GenRA)(VideoEXIT)

 

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2019 Biotechnology Sector and Artificial Intelligence in Healthcare

Reporter: Aviva Lev-Ari, PhD, RN

 

AI Ushers in a New Era

The implications of AI, cloud-based technologies and increased R&D focus have lent a competitive edge to companies within the biotech space. The use of AI has gradually begun to revolutionize research activities in the industry as it can drastically reduce time and costs involved in developing life-saving drugs.

Let’s take a look at some instances on how AI is being used to advance in biotech. AiCure has developed an application that uses AI to govern if and at what time the patient takes a pill. Moreover, it is now being used regularly in many clinical trials. SOPHiA Genetics ‘ AI system is used for genomics analysis of next-generation sequencing data from hospitals and research institutions globally.

Moreover, Illumina ILMN released an open source artificial intelligence software for discovering previously overlooked noncoding mutations in patients with rare genetic diseases in the beginning of 2019.

In fact, J&J JNJ , Pfizer PFE and Novartis NVS have tie-ups with IBM’s Watson Health. Per the deals, the companies can use Watson Health’s AI solutions and applications for drug discovery and to accelerate cancer research efforts.

SOURCE

https://m.nasdaq.com/article/biotechnology-market-on-a-tear-5-etfs-in-spotlight-cm1128200

 

The biotech industry has kept its promise for solid returns so far. The rally in some major biotechnology indexes reflects the same. In this context,

SOURCE

https://m.nasdaq.com/article/biotechnology-market-on-a-tear-5-etfs-in-spotlight-cm1128200

BioPharma

Novartis AG (NVS): Free Stock Analysis Report

Eli Lilly and Company (LLY): Free Stock Analysis Report

Roche Holding AG (RHHBY): Free Stock Analysis Report

Pfizer Inc. (PFE): Free Stock Analysis Report

Johnson & Johnson (JNJ): Free Stock Analysis Report

ALPS Medical Breakthroughs ETF (SBIO): ETF Research Reports

Principal Healthcare Innovators Index ETF (BTEC): ETF Research Reports

Virtus LifeSci Biotech Products ETF (BBP): ETF Research Reports

SPDR S&P Biotech ETF (XBI): ETF Research Reports

Spark Therapeutics, Inc. (ONCE): Free Stock Analysis Report

Illumina, Inc. (ILMN): Free Stock Analysis Report

ARK Genomic Revolution Multi-Sector ETF (ARKG): ETF Research Reports

SOURCE

To read this article on Zacks.com click here.

Zacks Investment Research

 

2019 M&A in Biotech

Mergers and acquisitions (M&As) are dominating the sector as sluggishness in mature products has forced companies to explore acquisitions to bolster their pipeline. The biggest deal of the year was Bristol-Myers’ acquisition offer of $74 billion to buy Celgene. Also, Eli Lilly and Company LLY has announced that it will take over Loxo Oncology for $8 billion to broaden its oncology suite to precision medicines or targeted therapies. (read: What’s Behind the Biotech ETF Rally to Start 2019? )

Several other large-cap pharma as well as bigger biotech companies are entering collaboration deals with smaller ones to boost their pipeline. Notably, Swiss pharma giant Roche Holdings RHHBY has bet big on U.S.-based gene therapy company Spark Therapeutics ONCE in an effort to strengthen its presence in gene therapy. Similarly, in order to develop gene therapies targeting rare indications, Biogen has offered to buy Nightstar Therapeutics.

Furthermore, in-licensing deals are consistently rising with bigwigs partnering with smaller and mid-sized players that own promising mid-to-late stage pipeline candidates or interesting technology.

SOURCE

https://m.nasdaq.com/article/biotechnology-market-on-a-tear-5-etfs-in-spotlight-cm1128200

 

Takeda-Novartis, Daiichi-AZ and more—FiercePharmaAsia
Takeda sells meds to Novartis and J&J; Daiichi’s AZ-shared HER2 antibody-drug conjugate hits key trial goal; Sun scouts for Chinese partner.
Takeda HQ
Novartis buys Takeda’s Xiidra, gets 400 staffers in $3.4B deal
Novartis hopes the deal, potentially worth $5.3 billion, could better position itself in front-of-the-eye therapies.
Asia Map
AZ, BeiGene, Kangmei and more—FiercePharmaAsia
AZ warns of slower China growth; BeiGene chief ranks among highest-paid biopharma CEOs; Kangmei faces delisting over huge accounting “error.”
Sanofi Pasteur HQ
After safety scare, Sanofi’s Dengvaxia nabs limited FDA nod
The FDA limited Dengvaxia to older children and teenagers living in endemic regions—and only if a diagnostic test confirms a prior dengue infection.
Takeda US facility
Takeda’s new Trintellix ad celebrates everyday wins
Takeda highlights everyday joys in new TV ads for major depressive disorder treatment Trintellix.
ReputationSign
HIV drugmakers ViiV, Gilead top pharma reputation survey
Pharma’s reputation is holding steady with patient groups with an annual study finding 41% giving pharma good marks, similar to 43% the year before.
Asia Map
PD-1 royalty dispute, Takeda and more—FiercePharmaAsia
Nobel laureate wants bigger PD-1 revenue cut; Takeda scouts buyers for Latin America business; Chinese genomics investor is forced out of U.S. firm.
Takeda scouts buyers for Latin American business: report
Takeda sold its Brazil-based unit Multilab right after it confirmed its plan to buy Shire, and now it’s reportedly mulling another sale in the region.
Woman typing on computer
Repackager recalls 40 lots of tainted losartan—News of Note
CDMOs Cambrex and Ajinomoto Bio-Pharma Services upgraded manufacturing plants, Takeda scored an albumin approval via its Shire deal, and more.
Darzalex
NICE limits coverage of J&J, Takeda myeloma combo
J&J’s Darzalex is on track to nab a second first-line myeloma nod in the U.S., but its reimbursement journey in England hasn’t been so smooth.

Other related 260 articles published in this Open Access Online Scientific Journal include the following:

https://pharmaceuticalintelligence.com/?s=Artificial+Intelligence

To access 260 articles:

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Select CATEGORY

Artificial Intelligence per Ontology on this topic [multiple nested categories]

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IBM’s Watson Health division – How will the Future look like?

Reporter: Aviva Lev-Ari, PhD, RN

 

Comment regarding Technology companies:

On April 18, 2019, IBM halting sales of Watson AI tool for drug discovery – STAT

https://www.statnews.com/2019/04/18/ibm-halting-sales-of-watson-for-drug-discovery/?utm_source=STAT+Newsletters

 

LPBI Group’s view on this news from IBM has few parts:

  • We believe that IBM needed to reorganize its application development efforts using AI in the Watson Business Unit. Drug discovery was targeted for downsizing. Watson will continue development of applications for Diagnosis applications. The realignment at IBM Watson is related to performance in the last three quarters when revenues decrease was recorded.
  • IBM will focus on other health units to compete with Oracle’s venturez in Health.
  • Watson requires high performance most sophisticated hardware and software. This was IBM focus on the high end computing machines since mid 70s with Series 360. They will not abandon that mission to be #1 in the World in high end market.
  • LPBI Group’s IP is most suited for IBM Watson for Diagnosis. Therefore we as a Team decided not to remove IBM Watson from our Opportunities Map.
  • We will prioritize among the players in the IT Sector and IBM will be the second tier for 2019-2020.

 

STAT News: The past year has been a tumultuous one for IBM’s Watson Health division.

In June, the team that manages the supercomputer once touted as a revolution in cancer care started to scale back its hospital business, citing weak demand. In July, internal IBM documents revealed that the supercomputer often delivered cancer treatment advice that was not only incorrect, but unsafe for patients as well. In November, a mass exodus began to erode the elite team of medical specialists and engineers tasked with fixing the artificial intelligence software. And in December, Watson Health’s fallback strategy — expanding operations in China — began to unravel.

In spite of all of this, IBM CEO Ginni Rometty kicked off 2019 with a bold statement — that IBM would not roll back its use of Watson in health care. But as STAT national technology correspondent Casey Ross reported last week, IBM is now halting its development and sales of a drug discovery and development product that uses Watson artificial intelligence software.

For more stories like this from health tech industry giants like IBM, Amazon, Google, and Apple, subscribe to STAT Plus today. Members enjoy unlimited access to STAT Plus stories, subscriber-only networking events across the country, and intelligence reports on key industry trends.

SOURCE

From: STAT Plus <marketing@statnews.com>

Reply-To: STAT Plus <marketing@statnews.com>

Date: Wednesday, April 24, 2019 at 3:15 PM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: The latest from IBM Watson

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LIVE Day Three – World Medical Innovation Forum ARTIFICIAL INTELLIGENCE, Boston, MA USA, Monday, April 10, 2019

 

www.worldmedicalinnovation.org

 

The Forum will focus on patient interactions across care settings, and the role technology and data can play in advancing knowledge discovery and care delivery. The agenda can be found here.

https://worldmedicalinnovation.org/agenda/

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

represented by Founder & Director, Aviva Lev-Ari, PhD, RN will cover this event in REAL TIME using Social Media

@pharma_BI

@AVIVA1950

@PHSInnovation

#WMIF19 

Wednesday, April 10, 2019

7:00 am – 12:00 pm
7:30 am – 9:30 am
Bayer Ballroom

Innovation Discovery Grant Awardee Presentations

Eleven clinical teams selected to receive highly competitive Innovation Discovery Grants present their work illustrating how AI can be used to improve patient health and health care delivery. This session is designed for investors, entrepreneurs, investigators, and others who are interested in commercializing AI opportunities that are currently in development with support from the Innovation Office.

To view speakers and topics, click here.

Where AI Meets Clinical Care

Twelve clinical AI teams culled through the Innovation Discovery Grant program present their work illustrating how AI can be used to improve patient health and healthcare delivery. This session is designed for investors, entrepreneurs, investigators, and others who are interested in commercializing AI opportunities that are currently in development with support from the Innovation Office.

IDG logo

Peter Dunn, MD

Vice President, Perioperative Services and Healthcare System Engineering, MGH; Assistant Professor, Anesthesia, HMS

Using Deep Learning to Optimize Hospital Capacity Management

  • collaboration with @MIT @MGH
  • deploy mobile app across all Partners institutions

 

Kevin Elias, MD

Director, Gynecologic Oncology Research Laboratory, BH; Assistant Professor, HMS

Screening for Cancer Using Serum miRNA Neural Networks

  • cancer screening fragmented process – tests not efficient No screening for many common cancer type
  • Cervical, Breast, Colon, Ovarian Uterus Cancer
  • Serum miRNA multiple cancer types

 

Alexandra Golby, MD

Director, Image-Guided Neurosurgery, BH; Professor, Neurosurgery and Radiology, HMS

Using Machine Learning to Optimize Optical Image Guidance for Brain Tumor Surgery

  • optical visualization in Neurosurgery – to improve Brain Cancer surgery Tumor removal complete resection could cause neurological deficits
  • BWH original research on Neuronavigations, intraops MRI
  • New Tool Real Time: Color code tumors using light diagnostics with machine learning
  • GUIDING Brain surgery, applicable for Breast Cancer
  • iP filling prototype creation, testing, pre-clinical testing, clinical protocol established academic-industrial partnerships
  • AI based – World 1st guided neurosurgery

 

Jayashree Kalpathy-Cramer, PhD

Director, QTIM Lab, MGH; Associate Professor, Radiology, HMS

DeepROP: Point-of-Care System for Diagnosis of Plus Disease in Retinopathy of Prematurity

  • Prematurity 1250 gr <31 weeks f gestation
  • ROP – Retinopathy of prematurity (ROP)
  • Images annotated Plus/not plus – algorithm for rating images “normal” or “plus”
  • DeepROP Applicationsinto Camera for data acquisition, iPhone

 

Jochen Lennerz, MD, PhD

Associate Director, Center for Integrated Diagnostics, MGH; Assistant Professor, HMS

Predicting Unnecessary Surgeries in High-Risk Breast Lesions

  • 10% reduction of high risk lesion equivalent to $1.4Billion in cost savings
  • Funding for Production line

Bruno Madore, PhD

Associate Professor, Radiology, BH, HMS

Sensor Technology for Enhanced Medical Imaging

  • ML Ultrasound – Organ configuration Motion (OCM) sensor
  • Hybrid MRI-ultrasound acquisitions
  • Long term vision – collaboration with Duke for a wireless device

 

Jinsong Ouyang, PhD

Physicist, MGH; Associate Professor, HMS

Training a Neural Network to Detect Lesions

  • Approach – train a NN using artificially inserted lesions

APPLICATIONS:

  • Build unlimitted number of training sets using small 15-50 human data sets generated
  • bone lession detection using SPECT
  • cardiac detect myocardial perfusion SPECT
  • Tumor detection PET
  • Volume detection/locatization of artificial Spinal Lesions (L1-L5)

 

David Papke, MD, PhD

Resident, Surgical Pathology, BH; Clinical Fellow, HMS

Augmented Digital Microscopy for Diagnosis of Endometrial Neoplasia

See tweet

 

Martin Teicher, MD, PhD

Director, Developmental Biopsychiatry Research Program, McLean; Associate Professor, Psychiatry, HMS

Poly-Exposure Risk Scores for Psychiatric Disorders

  • MACE Scale – psychopathology development – collinearity
  • Identifying sensitivity period predictors of major depression
  • predicting risk in adolescence – dataset with high collinearity
  • Onset of depression age 10-15
  • 50% assessment exposure to adversity – based on neuroimaging
  • Analytics and AI longitudinal studies

 

 

Christian Webb, PhD

Director, Treatment and Etiology of Depression, Youth Lab, McLean; Assistant Professor, Psychiatry, HMS

Leveraging Machine Learning to Match Depressed Patients to the Optimal Treatment

  • 4-8 wks of treatment till psychotropic drugs work
  • Data driven approaches: ML can match better patients to antidepressant treatments (Zoloft vs Placebo responder /non responder)?
  • Large number of variables prediction, prognosis calculator, good vs poor outcome
  • Better on Zoloft vs Placebo

 

Brandon Westover, MD, PhD

Executive Director, Clinical Data Animation Center, MGH; Associate Professor, Neurology, HMS
  • seizure, prediction of next attack
  • EEG readings – accurate diagnosis on epilepsy
  • 50 million World wide
  • automated epilepsy detection
  • @MGH – 1,063 EEGs 88,000 spikes 7 experts scored – not all agreed
  • How well can experts identify spikes?
  • Super spike detector is better than Experts – False positive 60% 87% Sensitivity vs 10% and 87% by AI
Moderator: David Louis, MD
  • Pathologist-in-Chief, MGH; Benjamin Castleman Professor of Pathology, HMS
Moderator: Clare Tempany, MD
  • Vice-Chair, Radiology Research, BH; Ferenc Jolesz MD Professor of Radiology, HMS
9:30 am – 10:00 am
10:00 am – 10:30 am
Bayer Ballroom

1:1 Fireside Chat: Stefan Oelrich, Member of the Board of Management; President, Pharmaceutical, Bayer AG

Introduction by: John Fish
  • CEO, Suffolk; Chairman of Board Trustees, Brigham Health
Moderator: Betsy Nabel, MD
  • President, Brigham Health; Professor of Medicine, HMS
  • Member of the Board of Management, Bayer AG; President, Pharmaceutical, Bayer AG

Chief Digital Officers

  • Leaders at the top needs to understand AI
  • Millennials needs to fill Baby boomer retiring
  • Boston – funding Research by NIH by private investment technology transfer to commercialization
  • Career advice: Academia is the first step for credibility move to Big Pharma, create own company
  • America economic strength built on innovation in Healthcare to invest
  • Leadership at Bayer: “Culture eat strategy for Breakfast”
  • AI overcoming barriers – AI improving what we know Medical imaging human vs machine – AI is the new norm – platforms Imaging AI device to detect Hypertension more accurately development of Bayer and Merck – Bayer leader in Radiology
  • Clinical research End point to reach compare
  • Future billion end point which therapeutic pathway is best for which patient
  • Incentives for risky strategy
  • Motivation to collaborate in Boston: Cardiology with broad Institute
  • BWH data and algorithms to increase knowledge
  • Pricing medicine around the World
  • US system in-transparent – patients do not understand Price of meds Rebates to Payers
  • Medical Part B – no pass to Rebates price tied to value
  • As industry – innovations in Pharma reduce healthcare costs Germany 15% of HealthCare on Drugs, generics, “Patented medicine 4%” of all Best in Europe
  • beak silos
  • In US training physicians to lead innovations
10:30 am – 11:00 am
Bayer Ballroom

1:1 Fireside Chat: Deepak Chopra, MD, Founder, The Chopra Foundation

Moderator: Rudolph Tanzi, PhD
  • Vice-Chair, Neurology, Director, Genetics and Aging Research Unit, MGH; Joseph P. and Rose F. Kennedy Professor of Neurology, HMS
  • IMAGING of Brains of Women in Meditation – enlongate telemeres
  • inflammation decrease – Sleep health interactions exsercise learning new things diet
  • flashing from brain wastes – amaloydosis AD – 35 genes variance leading to disease
  • Founder, The Chopra Foundation – Body-Mind Connection
  • AI – re-invest our bodies Telemeres, transferdomics,
  • Nutrition, sleep, excercise, BP, HR, sympathetic vs non sympatheric nervous system breathing pattern, – microbiome subjective experience with Vitals emotional well being
  • emersive augmented
  • longer Telemerese – anti aging correlation
  • biomarkers vs states of energy
  • wisdom best knowledge for self awareness – highest intelligence – NOT artificial
  • Thoughts on being aware
11:00 am – 11:50 am
Bayer Ballroom

Using AI to Predict and Monitor Human Performance and Neurological Disease

In the quest for effective treatments aimed at devastating neurological diseases like Alzheimer’s and ALS, there is a critical need for robust methods to predict and monitor disease progression. AI-based approaches offer promise in this important area. Panelists will discuss efforts to map movement-related disorders and use machine learning to predict the path of disease with imaging and biomarkers.

  • Chief of Neurology, Co-Director, Neurological Clinical Research Institute, MGH; Julieanne Dorn Professor of Neurology, HMS
  • Chief Scientist, Dolby Laboratories Stanford & Adobe – measuring experience
  • convergence of skills
  • internal wellness measured in the ear, motions
  • Stimulate Vagal nerve through the ear for depression treatment
  • Legislation in CA contribution to spaces
  • Global Therapeutic Head, Neuroscience Janssen Research & Development
  • Disease starts earlier Biogen contributions in the field
  • measurement surrogate indicators for outcome given interventions
  • Autism-spectrum not one disease
  • AI will enhance the human competence for measurement
  • UK based efforts to share dat and launch programs for Dementia
  • Conditions of Brain & Mind – declining cognitive
  • Democratization of discovery
  • AI benefit iterative process in changing and improving Algorithms — FDA approved algorithm needs several versions in the future
  • Complexity of CNS Polygenic gene scores
  • Dynamics of AI
  • EVP and CMO, Biogen
  • MS – follow patients, patient reporting in 10 centers , vision cognitions –
  • Obtain measurement even on normal people for early detection – FDA introduced Stage 1,2,3 Biomarker based
  • Newborn Kit of screening teat early helps
  • Home monitoring at Home for onset of AD

Dr. Isaac Galatzer-Levy – NYU & AiCure

  • All CNS diseases are heterogeneous
  • ML requires collaboration
  • AiCure – Medication adherence monitoring from Voice of patients
  • Sampling populations – cell phone
  • Re-investigate studies that have failed with new AI tools
11:50 am – 12:50 pm
Bayer Ballroom

Disruptive Dozen: 12 Technologies that will reinvent AI in the Next 12 Months

The Disruptive Dozen identifies and ranks the AI technologies that Partners faculty feel will break through over the next year to significantly improve health care.

  • innovations, technologies close to make to market

#12 David Ahern – Mental Health in US closing the Gap

#11 David Ting – Voice first

#10 Bharti Khurana – Partners Violence

#9 Gilberto Gonzales – Acute Stroke care

#8 James Hefferman – Burden og Health care ADM

#7 Samuel Aronson – FHIR Health information exchange

#6 Joan Miller – AI for eye health

#5 Brsndon Westover – A window to the Brain

#4 Rochelle Walensky – Automated detection of Malaria

#3 Annette Kim – Streamlining Diagnosis 

  #2 Thomas McCoy – Better Prediction of Suicide risk

  #1 Alexandra Golby – Reimagining Medical Imaging 

 

Moderator: Jeffrey Golden, MD
  • Chair, Department of Pathology, BH; Ramzi S. Cotran Professor of Pathology, HMS
  • Associate Chief, Infection Control Unit, MGH; Assistant Professor, Medicine, HMS
1:00 pm – 1:10 pm
Bayer Ballroom

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LIVE Day Two – World Medical Innovation Forum ARTIFICIAL INTELLIGENCE, Boston, MA USA, Monday, April 9, 2019

 

www.worldmedicalinnovation.org

 

The Forum will focus on patient interactions across care settings, and the role technology and data can play in advancing knowledge discovery and care delivery. The agenda can be found here.

https://worldmedicalinnovation.org/agenda/

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

represented by Founder & Director, Aviva Lev-Ari, PhD, RN will cover this event in REAL TIME using Social Media

@pharma_BI

@AVIVA1950

@PHSInnovation

#WMIF19 

Tuesday, April 9, 2019

7:00 am – 8:00 am
7:00 am – 5:00 pm
7:40 am – 7:50 am
Bayer Ballroom

Opening Remarks

  • Chief Innovation Officer, PHS; President, Partners HealthCare International
7:50 am – 8:40 am
Bayer Ballroom

Implementing AI in Cancer Care

With AI-enabled care strategies and digital technologies, clinicians and patients are embracing new approaches to improve the lives of cancer patients through enhanced diagnosis and treatment. These include AI-guided tools for more precise methods of predicting risk, more effective screening strategies, patient data driven insights  and more personalized treatments. Panelists will engage on how these and other innovations are enabling a new era of cancer care.

  • Chief, Breast Imaging Division, MGH; Professor of Radiology, HMS
  • FDA
  • President and Co-Founder, LunaDNA
  • Patients contribute personal data get share in the company
  • democratization by AI use
  • unrepresented population in research
  • education on technology
  • Retrospective and longitudinal studies
  • Bid Trust engaging responsively
  • Delta Electronics Professor, Electrical Engineering and Computer Science Department, MIT
  • developper of AI based applications @MGH Cancer Center
  • Training AI on 3% of population vs randomized that has its bias of patient selection
  • no standards of publishing AI in medicine
  • AI to help women
  • Integration of systems to help patients
  • Director, Cancer Genome Analysis, Broad Institute; Professor, Pathology, HMS
  • AI for early detection
  • big data analysis – noise vs point of signals
  • drug resistance using genomics
  • AI – regulate the type information reviewed by doctors
  • data acquisition and monitoring along the life of the product not only till FDA approve it
  • Reporting adverse events
  • Data cost of sequencing is dropping, biomarkers,
  • regulatory needed to adopt AI and reimbursement starts at academic center followed by the entire country
  • CEO, insitro
  • AI for drug discovery
  • epigenetic effect on lesions
  • Physician are over promised on Genomics, asking them to use complex data from multiple source need be curated before it gets to Physicians
  • Reversed clinical trial vs randomized 30 years follow up
  • Data is anonymized used in research contributors get back own diagnosis genomics understanding

 

8:40 am – 9:30 am
Bayer Ballroom

Imagining Medicine in the Year 2054

In 1984 Isaac Asimov was asked to predict what life in 2019 would be like. Using the same aperture, we as what will constitute health care 35 years from now? Current trends suggest that there will be significant gains in immunotherapy, gene therapy, and breakthrough treatments for neurologic, cardiovascular and oncologic diseases. Panelists will draw on their visionary perspective and will reflect on what to expect and why.

Moderator: Keith Flaherty, MD
  • Director, Clinical Research, Cancer Center, MGH; Professor of Medicine, HMS
  • CEO, Flagship Pioneering
  • Vice Chair for Scientific Innovation, Department of Medicine, BH; Associate Professor of Medicine, HMS
  • Director, Cellular Immunotherapy Program, Cancer Center, MGH; Assistant Professor, Medicine, HMS
  • Vice-Chair, Neurology, Director, Genetics and Aging Research Unit, MGH; Joseph P. and Rose F. Kennedy Professor of Neurology, HMS
9:30 am – 9:50 am
9:50 am – 10:15 am
Bayer Ballroom

1:1 Fireside Chat: Ash Carter, U.S. Secretary of Defense (2015 – 2017)

Moderator: Gregg Meyer, MD
  • Chief Clinical Officer, PHS; Professor of Medicine, HMS; 2019 Forum Co-Chair
  • U.S. Secretary of Defense (2015–2017)
10:15 am – 10:40 am
Bayer Ballroom

1:1 Fireside Chat: Honorable Alex Azar II, Secretary of Health and Human Services

Moderator: Gregg Meyer, MD
  • Chief Clinical Officer, PHS; Professor of Medicine, HMS; 2019 Forum Co-Chair
  • 24th Secretary of Health and Human Services
  • quality cate means outcomes
  • Pricing Transparency by HMOs and Hospitals
  • Plan D – instant electronic to Drug Pricing information
  • Medicare moves away from Procedure based payment
  • Data on services, drugs and procedures in a Patient-centered system
  • Big data, pricing information, CMS
  • AI inspector General – Claims – AI – do get yield
  • AI in procurement
  • AI for services to Medicare – prescription Tools for advising Patients on best drug to use based on medcial information
  • Patient HC information is owned by Pations and is portable
  • Blue Data 2.0 – access record by patients @CMS
10:40 am – 11:30 am
Bayer Ballroom

CEO Roundtable

Chief executives share perspectives on the impact of AI on their respective companies and industry segments. Panelists will discuss their views of AI, how AI figures into their organizations’ current product and investment strategies, and how they are measuring return on existing AI investments. The panel will also address opportunities and challenges surrounding AI, ranging from workforce needs to managing bias in AI development.

Moderator: Anne Klibanski, MD
  • Interim President and CEO, Chief Academic Officer, PHS; Laurie Carrol Guthart Professor of Medicine, HMS; 2019 Forum Co-Chair
  • Partnerships between companies like : GE, Phillips, Siemens
  • CEO, Philips
  • efficiencies and outcomes
  • adaptive intelligence to be integrated AI 1.8Billion Euro invested 600 scientists
  • collaboration with Dana Farber
  • Design thinking – work with clinicians to get insights on experience with technologies
  • system change for delivery of care
  • Open API – federated data architecture EMR companies will also need to adapt
  • Phillips builds centers in Pittsburgh, Cambridge, Amsterdam, Paris
  • EVP, Head, Pharmaceuticals Research and Development, Bayer AG
  • AI – R&D efficiency
  • Disruptive approaches optimization of synthesis of chemical reactions productivity and selection of molecules
  • In house data science expertise vs image pattern recognition of HTN collaboration with Merck
  • Collaboration with MIT on clinical Trials
  • changing provides vs longitudinal care
  • Access to talent – Data scientists Amazon is a competitor on talent for AI SKILLS DOMAIN EXPRET TOPIC
  • R&D AT BAYER – DATA SCIENCE IN each division
  • CEO, Siemens Healthineers
  • 400 research collaborations
  • “analog” way innovations generations
  • CEO, GE Healthcare
  • HC – Clinical command center in Hospitals collaboration with Partners
  • Investment is in platforms vs applications – Edison platform tool kits – Radiologist will develop their own on top of PLATFORMS from GE
  • Clinicians productivity will change with AI
  • Data scientist new identity – bigger developers of systems
11:30 am – 11:35 am
Bayer Ballroom
11:35 am – 11:45 am
11:45 am – 1:00 pm

Discovery Cafe Sessions

Lunch with Experts: Intensive sessions addressing cutting-edge artificial intelligence topics.

Provider Back Office of the Future

The application of AI-based technologies to the business side of health care — including functions such as billing, payment, and insurance claims management — could lead to significant improvements in health care operations and efficiency, with billions of dollars in savings each year. Panelists will discuss emerging tools and technologies as well as the opportunities and pitfalls of using AI to innovate and automate back office functions.

Moderator: Peter Markell, EVP, Administration and Finance, CFO and Treasurer, PHS

Inge Harrison, CNO/VP of Strategic Advisory Services, Verge Health

Kent Ivanoff, CEO, VisitPay

Mary Beth Remorenko, VP, Revenue Cycle Operations, PHS

Brian Robertson, CEO, VisiQuate

 

Chief Digital Strategy Officer Roundtable

With the advent of AI-enabled technologies, this session brings together leading chief digital health officers. The discussion will address tradeoffs in sequencing technology across academic medical centers; what technologies are being prioritized; and consumer expectations.

Moderator: Alistair Erskine, MD, Chief Digital Health Officer, PHS

Michael Anderes, Chief Innovation and Digital Health Officer, Froedtert Health; President, Inception Health

Adam Landman, MD, VP and CIO, BH; Associate Professor of Emergency Medicine, HMS

Aimee Quirk, CEO, innovationOchsner

Richard Zane, MD, Chief Innovation Officer, UCHealth; Professor and Chair,Department of Emergency Medicine, University of Colorado School of Medicine

 

Innovation Fellows: A New Model of Collaboration

The Innovation Fellows Program provides experiential career development opportunities for future leaders in health care. It facilitates personnel exchanges between Harvard Medical School staff from Partners’ hospitals and participating biopharmaceutical, device, venture capital, digital health, payor and consulting firms. Fellows and Hosts learn from each other as they collaborate on projects ranging from clinical development to digital health and artificial intelligence. Learn how this new model of collaboration can deliver value and lead to broader relationships between industry and academia.

Moderator: Seema Basu, PhD, Market Sector Leader, Innovation, PHS

Nathalie Agar, PhD, Research Scientist, Neurosurgery, BH; Associate Professor, Neurosurgery, Radiology, HMS

Paul Anderson, MD, PhD, Chief Academic Officer, BH; SVP, Research, BH; K. Frank Austen Professor of Medicine, HMS

Laurie Braun, MD, Partners Innovation Fellow, MGH and Boston Pharmaceuticals; Instructor in Pediatrics, HMS

David Chiang, MD, PhD, Research Fellow, BH; Innovation Fellow, Boston Scientific

David Feygin, PhD, Chief Digital Health Officer, Boston Scientific

Peter Ho, MD, PhD, CMO, Boston Pharmaceuticals

Harry Orf, PhD, SVP, Research, MGH; Principal Associate, HMS

 

Last Mile: Fully Implementing AI in Healthcare

This session will focus on how radiology and pathology specialties are currently applying AI in the clinic. Where will it be built out first? What are the barriers and how will these challenges be overcome?

Moderator: Keith Dreyer, DO, PhD, Chief Data Science Officer, PHS; Vice Chairman, Radiology, MGH; Associate Professor, Radiology, HMS

Katherine Andriole, PhD, Director of Research Strategy and Operations, MGH & BWH CCDS; Associate Professor, Radiology, HMS

Samuel Aronson, Executive Director, IT, Personalized Medicine, PHS

Peter Durlach, SVP, Healthcare Strategy & New Business Development, Nuance

Seth Hain, VP of R&D, Epic

Jonathan Teich, MD, PhD, Chief Medical Information Officer, InterSystems; Emergency Medicine, BH

 

Reimagining Disease Management

The management of disease has become vastly more challenging, both for patients and providers. AI-based technologies promise to improve and streamline patient care through a variety of approaches. This session will feature a discussion of these new tools and how they can enhance patient engagement and optimize care management.

Moderator: Sree Chaguturu, MD, Chief Population Health Officer, PHS; Assistant Professor, Medicine, HMS

Murray Brozinsky, Chief Strategy Officer, Conversa

Jean Drouin, MD, CEO, Clarify Health Solutions

Julian Harris, MD, President, CareAllies

Erika Pabo, MD, Chief Health Officer, Humana Edge; Associate Faculty, Ariadne Labs; Associate Physician, BH; Instructor, HMS

 

Standards and Regulation: The Emerging AI Framework

As the health care industry faces an explosion of AI-based tools, the FDA’s approach to these technologies is evolving. This session will focus on the agency’s approach to AI-based products, how to calculate the risk profile of these new technologies, and the challenges of securing adequate data rights.

Moderator: Brent Henry, Member, Mintz Levin

Bethany Hills, Member/ Chair, FDA Practice, Mintz Levin

Michelle McMurry-Heath, MD, PhD, VP, Global Regulatory Affairs and International Clinical Evidence, Johnson & Johnson Medical Devices

Bakul Patel, Associate Director, Digital Health, FDA

Michael Spadafore, Managing Director, Sandbox Industries

 

From Startup to Impact (Provider Solutions)

This session will introduce you to five leading startup companies who will each share their respective impact in delivery provider solutions in ten-minute pitches.

Moderator: Meredith Fisher, PhD, Partner, Partners Innovation Fund, PHS

Moderator: James Stanford, Managing Director, Fitzroy Health

William Grambley, COO, AllazoHealth

Gal Salomon, CEO, CLEW

Siddarth Satish, CEO, Gauss Surgical

Pelu Tran, CEO, Ferrum Health

Ed Zecchini, CIO, Remedy Partners

1:00 pm – 1:10 pm
1:10 pm – 2:00 pm
Bayer Ballroom

China: AI Enabled Healthcare Leadership

China’s health care system faces major challenges — and its population is aging more rapidly than nearly every other country. To help address these problems, the Chinese health technology sector is strongly embracing AI. What are the most exciting applications? What lessons does China’s early forays into AI-enabled patient care hold for other health care systems?

Moderator: James Bradner, MD
  • President, Novartis Institutes for BioMedical Research
  • Chief Innovation Officer, GE Healthcare
  • Analytics allowing higher throughput in China in Rural areas
  • Sepsis – detection is too late
  • data exhaust for facial recognition – anticipatory diagnosis
  • oncology tumor algorithm
  • CEO, Infervision
  • Medical imaging – four years to mature nodule detection
  • AI – no resale of data
  • Chairman and Co-Founder, Yidu Cloud
  • Medical records
  • Data privacy is personal consent if identification Passport level:
  • Doctor looking on Medical record need consent
  • Administration – clearance for access
  • Managing Partner, Qiming Venture Partners
  • AI HC companies execution to build companies
  • Valuation of all AI not only HC, dropped 30%
  • Real Doctor – 14 licensing for Internet medicine 90,000 patients a day are seen
  • Consumer EMR – Alibaba invested in
  • Investment in CRISPR
  • Invest in drug discovery in China
  • In China 150 programs of drug development of PD-1
  • Government  – 90% of patients go to Public Hospital which guard the data
  • Challenges AI in China — US – China Trade issue
  • CEO, Real Doctor Corporation Limited
  • Medical imaging 12 disease found from pictures build models to other 100 hospitals
  • small nodules detection
  • China-FDA no regulation established yet Learn from US FDA
2:00 pm – 2:30 pm
Bayer Ballroom

1:1 Fireside Chat: Mark Benjamin, CEO, Nuance

Moderator: Peter Slavin, MD
  • President, MGH; Professor, Health Care Policy, HMS
  • CEO, Nuance Communications
  • System produce NOTES from conversation, clinical language, notes read interactively by looking at other chart – LIVE EXAM more that an invoicing tool
  • patient case management made efficient
  • Documentation and Clinical notes embedded into the EHR enhance intelligence at Point-of-Care

 

2:30 pm – 3:00 pm
3:00 pm – 3:50 pm
Bayer Ballroom

Getting to the AI Investment Decision

The billions invested worldwide in AI-based health care technologies underscore the enthusiasm of global investors. But where are the greatest opportunities and what is the timeline to meaningful impact? In this panel, venture, private equity investors, and buy side analysts will discuss investment priorities, timelines, and key areas of interest

  • Partner, Partners Innovation Fund, PHS
  • When is the time right and when there is only a promise
  • VP, Venture and Managing Partner, Partners Innovation Fund, PHS
  • Looks like therapeutics but it is AI
  • Managing Director, Bain Capital Life Sciences
  • companies leveraging competencies
  •  Capital put to work what is it coming to do – specific value creation
  • Is the problem HC or an Academic Medical Center, i.e., MGH problem to solve
  • If no one at PHS willing to pay — let’s think again
  • Managing Partner, Polaris Partners
  • Data in Pharma companies are ready for AI application
  • algorithms and analytics
  • Value proposition
  • Language processing & ML – recognize patterns in consistant datasets – improve decision made in patient care
  • SVP, Strategy, Commercialization and Innovation, Amgen
  • Real data using AI for speeding drug discovery commercial application
  • predictive models for second MI with partner
  • Pilot study vs scaling up
  • Managing Director, Healthcare Group, Goldman Sachs
  • As AI algorithm mature, labor intensity curbed by AI
  • IPO
  • consolidation of big pharma
  • Partner, Google Ventures – started in 2008/9; Instructor in Medicine, BH
  • data quality needed for AI to avoid bias
  • Pharma is interested in Drugs not in Targets
  • Translator between technology and healthcare
  • Teach computer the rules to go then beating its creator unanticipated modes
  • IT is different in various industries more than West Coast vs East Coast
3:50 pm – 4:20 pm
Bayer Ballroom

1:1 Fireside Chat: Robert Bradway, CEO, Amgen

  • Partner, Atlas Venture
  • CEO, Amgen
  • DeCode Genetics acquired by Amgen
  • AI is in the beginning Rapata and Evenity (romosozumab) risk of fractures – review large images archives
  • Migraine only digital health  – this is not a big area for Amgen
  • Transparency
  • Encouraged to role back the Rebate Program the sickest pay to high – policy changes
  • Part 4
  • Rapata – lower LDL reduce risk for stroke MI 600Billion fighting Heart disease – price lowered 60% patients are directed to the more expensive product
  • Investment in Biosimilars and biologics made available free resources
  • risk is Washington, generics may become the rule for biologics
  • no favor innovating products vs Biosimilars
  • ObamaCare create 12 years of data exclusivity for biologics
  • 90% of prescription is generic products
  • cost of CVD in 2019 is a fraction of the cost 15 years ago
  • CURE – is used for Cancer at what price HEP C – is a cure very expansive
  • Meaning of innovations create frameworks for saving live
4:20 pm – 5:10 pm
Bayer Ballroom

Consumer Healthcare and New Models of Care Delivery

Al is powering a revolution in consumer health care, giving patients a deeper role in monitoring their own health and spawning new models of care delivery. Many health care organizations are increasingly focused on creating a digital “front door” for patients – a single gateway to mobile apps and other online services. Panelists will also discuss the role of remote monitoring and virtual care programs as well as the role of Al in care redesign and workflow.

Moderator: Diana Nole
  • CEO, Wolters Kluwer Health
  • President, Global Strategy Group, Samsung; Founder, CareVisor
  • Real time sensing to deliver realtime care plan: Human Avatar
  • AI is hidden
  • communication varies by generations phone vs SMS
  • VP and Global CTO, Sales, Dell EMC
  • IOT – scale
  • social media – peer pressure
  • President, Health Platforms, Verily Life Sciences
  • AI applied in diet management with images of snacks
  • Co-production of Health 50s-60s concept Co-Production health by patients give patients information and they will co-produce their healthier life style
  • VP and Chief Health Officer, IBM Corporation
  • AI continues to improve – actionable insights
  • AI augmented humanity
  • In China a Team of oncologist meet with entire families to discuss plan of care Cancer patients for GrandMa,
  • SVP, Head of Innovation and Health Equity, Microsoft Healthcare
  • AI – sequence T cells
5:15 pm – 5:25 pm
Bayer Ballroom

BioBank Award Announcement

  • Third place MGH – Computational Pathology
  • First Prize – $12,000 UPittsburg – Dept Biomedical Informatics – principal components
  • First Prize – IBM Center for Computational Health – supervised algorithm
5:30 pm – 6:30 pm

 

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Google, Verily’s Uses AI to Screen for Diabetic Retinopathy

Reporter : Irina Robu, PhD

Google and Verily, the life science research organization under Alphabet designed a machine learning algorithm to better screen for diabetes and associated eye diseases. Google and Verily believe the algorithm can be beneficial in areas lacking optometrists.

The algorithm is being integrated for the first time in a clinical setting at Aravind Eye Hospital in Madurai, India where it is designed to screen for diabetic retinopathy and diabetic macular edema. After a patient is imaged by trained staff using a fundus camera, the image is uploaded to the screening algorithm through management software. The algorithm then analyzes the images for the diabetic eye diseases before returning the results.

Numerous AI-driven approaches have lately been effective in detecting diabetic retinopathy with high accuracy. An AI-based grading system was able to effectively diagnose two patients with the disease. Furthermore, an AI-driven approach for detecting an early sign of diabetic retinopathy attained an accuracy rate of more than 98 percent.

According to the R. Usha Kim, Chief of retina services at the Aravind Eye Hospital the algorithm permits physicians to work closely with patients on treatment and management of their disease, whereas increasing the volume of screenings we can perform. Automated grading of diabetic retinopathy has possible benefits such as increasing efficiency, reproducible, and coverage of screening programs and improving patient outcomes by providing early detection and treatment.

Even if the technology sounds promising, current research show there are long way until it can directly transfer from the lab into clinic.

SOURCE
https://www.healthcareitnews.com/news/google-verily-using-ai-screen-diabetic-retinopathy-india

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