Search

Your search keyword '"Holmes, Jayme"' showing total 31 results
Start Over Author "Holmes, Jayme"
31 results on '"Holmes, Jayme"'

4. Pharos 2023:an integrated resource for the understudied human proteome

Author

Kelleher, Keith J., Sheils, Timothy K., Mathias, Stephen L., Yang, Jeremy J., Metzger, Vincent T., Siramshetty, Vishal B., Nguyen, Dac-Trung, Jensen, Lars Juhl, Vidovic, Dusica, Schurer, Stephan C., Holmes, Jayme, Sharma, Karlie R., Pillai, Ajay, Bologa, Cristian G., Edwards, Jeremy S., Mathe, Ewy A., Oprea, Tudor, Kelleher, Keith J., Sheils, Timothy K., Mathias, Stephen L., Yang, Jeremy J., Metzger, Vincent T., Siramshetty, Vishal B., Nguyen, Dac-Trung, Jensen, Lars Juhl, Vidovic, Dusica, Schurer, Stephan C., Holmes, Jayme, Sharma, Karlie R., Pillai, Ajay, Bologa, Cristian G., Edwards, Jeremy S., Mathe, Ewy A., and Oprea, Tudor

Abstract

The Illuminating the Druggable Genome (IDG) project aims to improve our understanding of understudied proteins and our ability to study them in the context of disease biology by perturbing them with small molecules, biologics, or other therapeutic modalities. Two main products from the IDG effort are the Target Central Resource Database (TCRD), which curates and aggregates information, and Pharos, a web interface for fusers to extract and visualize data from TCRD. Since the 2021 release, TCRD/Pharos has focused on developing visualization and analysis tools that help reveal higher-level patterns in the underlying data. The current iterations of TCRD and Pharos enable users to perform enrichment calculations based on subsets of targets, diseases, or ligands and to create interactive heat maps and UpSet charts of many types of annotations. Using several examples, we show how to address disease biology and drug discovery questions through enrichment calculations and UpSet charts.

Published
2023

6. Pharos 2023: an integrated resource for the understudied human proteome

Author

Kelleher, Keith J, primary, Sheils, Timothy K, additional, Mathias, Stephen L, additional, Yang, Jeremy J, additional, Metzger, Vincent T, additional, Siramshetty, Vishal B, additional, Nguyen, Dac-Trung, additional, Jensen, Lars Juhl, additional, Vidović, Dušica, additional, Schürer, Stephan C, additional, Holmes, Jayme, additional, Sharma, Karlie R, additional, Pillai, Ajay, additional, Bologa, Cristian G, additional, Edwards, Jeremy S, additional, Mathé, Ewy A, additional, and Oprea, Tudor I, additional

Published
2022
Full Text
View/download PDF

8. Getting Started with the IDG KMC Datasets and Tools

Author

Kropiwnicki, Eryk, primary, Binder, Jessica L., additional, Yang, Jeremy J., additional, Holmes, Jayme, additional, Lachmann, Alexander, additional, Clarke, Daniel J. B., additional, Sheils, Timothy, additional, Kelleher, Keith J., additional, Metzger, Vincent T., additional, Bologa, Cristian G., additional, Oprea, Tudor I., additional, and Ma'ayan, Avi, additional

Published
2022
Full Text
View/download PDF

10. Pharos 2023: an integrated resource for the understudied human proteome.

Author

Kelleher, Keith J, Sheils, Timothy K, Mathias, Stephen L, Yang, Jeremy J, Metzger, Vincent T, Siramshetty, Vishal B, Nguyen, Dac-Trung, Jensen, Lars Juhl, Vidović, Dušica, Schürer, Stephan C, Holmes, Jayme, Sharma, Karlie R, Pillai, Ajay, Bologa, Cristian G, Edwards, Jeremy S, Mathé, Ewy A, and Oprea, Tudor I

Published
2023
Full Text
View/download PDF

11. TCRD and Pharos 2021:mining the human proteome for disease biology

Author

Sheils, Timothy K., Mathias, Stephen L., Kelleher, Keith J., Siramshetty, Vishal B., Nguyen, Dac Trung, Bologa, Cristian G., Jensen, Lars Juhl, Vidović, Dušica, Koleti, Amar, Schürer, Stephan C., Waller, Anna, Yang, Jeremy J., Holmes, Jayme, Bocci, Giovanni, Southall, Noel, Dharkar, Poorva, Mathé, Ewy, Simeonov, Anton, Oprea, Tudor I., Sheils, Timothy K., Mathias, Stephen L., Kelleher, Keith J., Siramshetty, Vishal B., Nguyen, Dac Trung, Bologa, Cristian G., Jensen, Lars Juhl, Vidović, Dušica, Koleti, Amar, Schürer, Stephan C., Waller, Anna, Yang, Jeremy J., Holmes, Jayme, Bocci, Giovanni, Southall, Noel, Dharkar, Poorva, Mathé, Ewy, Simeonov, Anton, and Oprea, Tudor I.

Abstract

In 2014, the National Institutes of Health (NIH) initiated the Illuminating the Druggable Genome (IDG) program to identify and improve our understanding of poorly characterized proteins that can potentially be modulated using small molecules or biologics. Two resources produced from these efforts are: The Target Central Resource Database (TCRD) (http://juniper.health.unm.edu/tcrd/) and Pharos (https://pharos.nih.gov/), a web interface to browse the TCRD. The ultimate goal of these resources is to highlight and facilitate research into currently understudied proteins, by aggregating a multitude of data sources, and ranking targets based on the amount of data available, and presenting data in machine learning ready format. Since the 2017 release, both TCRD and Pharos have produced two major releases, which have incorporated or expanded an additional 25 data sources. Recently incorporated data types include human and viral-human protein-protein interactions, protein-disease and protein-phenotype associations, and drug-induced gene signatures, among others. These aggregated data have enabled us to generate new visualizations and content sections in Pharos, in order to empower users to find new areas of study in the druggable genome.

Published
2021

12. DrugCentral 2021 supports drug discovery and repositioning

Author

Avram, Sorin, Bologa, Cristian G., Holmes, Jayme, Bocci, Giovanni, Wilson, Thomas B., Nguyen, Dac Trung, Curpan, Ramona, Halip, Liliana, Bora, Alina, Yang, Jeremy J., Knockel, Jeffrey, Sirimulla, Suman, Ursu, Oleg, Oprea, Tudor I., Avram, Sorin, Bologa, Cristian G., Holmes, Jayme, Bocci, Giovanni, Wilson, Thomas B., Nguyen, Dac Trung, Curpan, Ramona, Halip, Liliana, Bora, Alina, Yang, Jeremy J., Knockel, Jeffrey, Sirimulla, Suman, Ursu, Oleg, and Oprea, Tudor I.

Abstract

DrugCentral is a public resource (http://drugcentral.org) that serves the scientific community by providing up-to-date drug information, as described in previous papers. The current release includes 109 newly approved (October 2018 through March 2020) active pharmaceutical ingredients in the US, Europe, Japan and other countries; and two molecular entities (e.g. mefuparib) of interest for COVID19. New additions include a set of pharmacokinetic properties for ∼1000 drugs, and a sex-based separation of side effects, processed from FAERS (FDA Adverse Event Reporting System); as well as a drug repositioning prioritization scheme based on the market availability and intellectual property rights forFDA approved drugs. In the context of the COVID19 pandemic, we also incorporated REDIAL-2020, a machine learning platform that estimates anti-SARS-CoV-2 activities, as well as the 'drugs in news' feature offers a brief enumeration of the most interesting drugs at the present moment. The full database dump and data files are available for download from the DrugCentral web portal.

Published
2021

14. TCRD and Pharos 2021: mining the human proteome for disease biology

Author

Sheils, Timothy K, primary, Mathias, Stephen L, additional, Kelleher, Keith J, additional, Siramshetty, Vishal B, additional, Nguyen, Dac-Trung, additional, Bologa, Cristian G, additional, Jensen, Lars Juhl, additional, Vidović, Dušica, additional, Koleti, Amar, additional, Schürer, Stephan C, additional, Waller, Anna, additional, Yang, Jeremy J, additional, Holmes, Jayme, additional, Bocci, Giovanni, additional, Southall, Noel, additional, Dharkar, Poorva, additional, Mathé, Ewy, additional, Simeonov, Anton, additional, and Oprea, Tudor I, additional

Published
2020
Full Text
View/download PDF

15. DrugCentral 2021 supports drug discovery and repositioning

Author

Avram, Sorin, primary, Bologa, Cristian G, additional, Holmes, Jayme, additional, Bocci, Giovanni, additional, Wilson, Thomas B, additional, Nguyen, Dac-Trung, additional, Curpan, Ramona, additional, Halip, Liliana, additional, Bora, Alina, additional, Yang, Jeremy J, additional, Knockel, Jeffrey, additional, Sirimulla, Suman, additional, Ursu, Oleg, additional, and Oprea, Tudor I, additional

Published
2020
Full Text
View/download PDF

18. Unexplored therapeutic opportunities in the human genome

Author

Oprea, Tudor I, Bologa, Cristian G, Brunak, Søren, Campbell, Allen, Gan, Gregory N, Gaulton, Anna, Gomez, Shawn M, Guha, Rajarshi, Hersey, Anne, Holmes, Jayme, Jadhav, Ajit, Jensen, Lars Juhl, Johnson, Gary L, Karlson, Anneli, Leach, Andrew R, Ma'ayan, Avi, Malovannaya, Anna, Mani, Subramani, Mathias, Stephen L, McManus, Michael T, Meehan, Terrence F, von Mering, Christian, Muthas, Daniel, Nguyen, Dac-Trung, Overington, John P, Papadatos, George, Qin, Jun, Reich, Christian, Roth, Bryan L, Schürer, Stephan C, Simeonov, Anton, Sklar, Larry A, Southall, Noel, Tomita, Susumu, Tudose, Ilinca, Ursu, Oleg, Vidovic, Dušica, Waller, Anna, Westergaard, David, Yang, Jeremy J, Zahoránszky-Köhalmi, Gergely, Oprea, Tudor I, Bologa, Cristian G, Brunak, Søren, Campbell, Allen, Gan, Gregory N, Gaulton, Anna, Gomez, Shawn M, Guha, Rajarshi, Hersey, Anne, Holmes, Jayme, Jadhav, Ajit, Jensen, Lars Juhl, Johnson, Gary L, Karlson, Anneli, Leach, Andrew R, Ma'ayan, Avi, Malovannaya, Anna, Mani, Subramani, Mathias, Stephen L, McManus, Michael T, Meehan, Terrence F, von Mering, Christian, Muthas, Daniel, Nguyen, Dac-Trung, Overington, John P, Papadatos, George, Qin, Jun, Reich, Christian, Roth, Bryan L, Schürer, Stephan C, Simeonov, Anton, Sklar, Larry A, Southall, Noel, Tomita, Susumu, Tudose, Ilinca, Ursu, Oleg, Vidovic, Dušica, Waller, Anna, Westergaard, David, Yang, Jeremy J, and Zahoránszky-Köhalmi, Gergely

Abstract

A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately two out of five proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.

Published
2018

19. DrugCentral 2018: an update

Author

Ursu, Oleg, primary, Holmes, Jayme, additional, Bologa, Cristian G, additional, Yang, Jeremy J, additional, Mathias, Stephen L, additional, Stathias, Vasileios, additional, Nguyen, Dac-Trung, additional, Schürer, Stephan, additional, and Oprea, Tudor, additional

Published
2018
Full Text
View/download PDF

20. Erratum: Unexplored therapeutic opportunities in the human genome

Author

Oprea, Tudor I., primary, Bologa, Cristian G., additional, Brunak, Søren, additional, Campbell, Allen, additional, Gan, Gregory N., additional, Gaulton, Anna, additional, Gomez, Shawn M., additional, Guha, Rajarshi, additional, Hersey, Anne, additional, Holmes, Jayme, additional, Jadhav, Ajit, additional, Jensen, Lars Juhl, additional, Johnson, Gary L., additional, Karlson, Anneli, additional, Leach, Andrew R., additional, Ma'ayan, Avi, additional, Malovannaya, Anna, additional, Mani, Subramani, additional, Mathias, Steven L., additional, McManus, Michael T., additional, Meehan, Terrence F., additional, von Mering, Christian, additional, Muthas, Daniel, additional, Nguyen, Dac-Trung, additional, Overington, John P., additional, Papadatos, George, additional, Qin, Jun, additional, Reich, Christian, additional, Roth, Bryan L., additional, Schürer, Stephan C., additional, Simeonov, Anton, additional, Sklar, Larry A., additional, Southall, Noel, additional, Tomita, Susumu, additional, Tudose, Ilinca, additional, Ursu, Oleg, additional, Vidovic´, Dušica, additional, Waller, Anna, additional, Westergaard, David, additional, Yang, Jeremy J., additional, and Zahoránszky-Köhalmi, Gergely, additional

Published
2018
Full Text
View/download PDF

21. Unexplored therapeutic opportunities in the human genome

Author

Oprea, Tudor I., primary, Bologa, Cristian G., additional, Brunak, Søren, additional, Campbell, Allen, additional, Gan, Gregory N., additional, Gaulton, Anna, additional, Gomez, Shawn M., additional, Guha, Rajarshi, additional, Hersey, Anne, additional, Holmes, Jayme, additional, Jadhav, Ajit, additional, Jensen, Lars Juhl, additional, Johnson, Gary L., additional, Karlson, Anneli, additional, Leach, Andrew R., additional, Ma'ayan, Avi, additional, Malovannaya, Anna, additional, Mani, Subramani, additional, Mathias, Stephen L., additional, McManus, Michael T., additional, Meehan, Terrence F., additional, von Mering, Christian, additional, Muthas, Daniel, additional, Nguyen, Dac-Trung, additional, Overington, John P., additional, Papadatos, George, additional, Qin, Jun, additional, Reich, Christian, additional, Roth, Bryan L., additional, Schürer, Stephan C., additional, Simeonov, Anton, additional, Sklar, Larry A., additional, Southall, Noel, additional, Tomita, Susumu, additional, Tudose, Ilinca, additional, Ursu, Oleg, additional, Vidović, Dušica, additional, Waller, Anna, additional, Westergaard, David, additional, Yang, Jeremy J., additional, and Zahoránszky-Köhalmi, Gergely, additional

Published
2018
Full Text
View/download PDF

22. Pharos:Collating protein information to shed light on the druggable genome

Author

Nguyen, Dac-Trung, Mathias, Stephen, Bologa, Cristian, Brunak, Soren, Fernandez, Nicolas, Gaulton, Anna, Hersey, Anne, Holmes, Jayme, Jensen, Lars Juhl, Karlsson, Anneli, Liu, Guixia, Ma'ayan, Avi, Mandava, Geetha, Mani, Subramani, Mehta, Saurabh, Overington, John, Patel, Juhee, Rouillard, Andrew D, Schürer, Stephan, Sheils, Timothy, Simeonov, Anton, Sklar, Larry A, Southall, Noel, Ursu, Oleg, Vidovic, Dusica, Waller, Anna, Yang, Jeremy, Jadhav, Ajit, Oprea, Tudor I, Guha, Rajarshi, Nguyen, Dac-Trung, Mathias, Stephen, Bologa, Cristian, Brunak, Soren, Fernandez, Nicolas, Gaulton, Anna, Hersey, Anne, Holmes, Jayme, Jensen, Lars Juhl, Karlsson, Anneli, Liu, Guixia, Ma'ayan, Avi, Mandava, Geetha, Mani, Subramani, Mehta, Saurabh, Overington, John, Patel, Juhee, Rouillard, Andrew D, Schürer, Stephan, Sheils, Timothy, Simeonov, Anton, Sklar, Larry A, Southall, Noel, Ursu, Oleg, Vidovic, Dusica, Waller, Anna, Yang, Jeremy, Jadhav, Ajit, Oprea, Tudor I, and Guha, Rajarshi

Abstract

The 'druggable genome' encompasses several protein families, but only a subset of targets within them have attracted significant research attention and thus have information about them publicly available. The Illuminating the Druggable Genome (IDG) program was initiated in 2014, has the goal of developing experimental techniques and a Knowledge Management Center (KMC) that would collect and organize information about protein targets from four families, representing the most common druggable targets with an emphasis on understudied proteins. Here, we describe two resources developed by the KMC: the Target Central Resource Database (TCRD) which collates many heterogeneous gene/protein datasets and Pharos (https://pharos.nih.gov), a multimodal web interface that presents the data from TCRD. We briefly describe the types and sources of data considered by the KMC and then highlight features of the Pharos interface designed to enable intuitive access to the IDG knowledgebase. The aim of Pharos is to encourage 'serendipitous browsing', whereby related, relevant information is made easily discoverable. We conclude by describing two use cases that highlight the utility of Pharos and TCRD.

Published
2017

23. DrugCentral 2018: an update.

Author

Ursu, Oleg, Holmes, Jayme, Bologa, Cristian G, Yang, Jeremy J, Mathias, Stephen L, Stathias, Vasileios, Nguyen, Dac-Trung, Schürer, Stephan, and Oprea, Tudor

Published
2019
Full Text
View/download PDF

24. Pharos: Collating protein information to shed light on the druggable genome

Author

Nguyen, Dac-Trung, primary, Mathias, Stephen, additional, Bologa, Cristian, additional, Brunak, Soren, additional, Fernandez, Nicolas, additional, Gaulton, Anna, additional, Hersey, Anne, additional, Holmes, Jayme, additional, Jensen, Lars Juhl, additional, Karlsson, Anneli, additional, Liu, Guixia, additional, Ma'ayan, Avi, additional, Mandava, Geetha, additional, Mani, Subramani, additional, Mehta, Saurabh, additional, Overington, John, additional, Patel, Juhee, additional, Rouillard, Andrew D., additional, Schürer, Stephan, additional, Sheils, Timothy, additional, Simeonov, Anton, additional, Sklar, Larry A., additional, Southall, Noel, additional, Ursu, Oleg, additional, Vidovic, Dusica, additional, Waller, Anna, additional, Yang, Jeremy, additional, Jadhav, Ajit, additional, Oprea, Tudor I., additional, and Guha, Rajarshi, additional

Published
2016
Full Text
View/download PDF

25. DrugCentral: online drug compendium

Author

Ursu, Oleg, primary, Holmes, Jayme, additional, Knockel, Jeffrey, additional, Bologa, Cristian G., additional, Yang, Jeremy J., additional, Mathias, Stephen L., additional, Nelson, Stuart J., additional, and Oprea, Tudor I., additional

Published
2016
Full Text
View/download PDF

27. Pharos: Collating protein information to shed light on the druggable genome.

Author

Dac-Trung Nguyen, Mathias, Stephen, Bologa, Cristian, Brunak, Soren, Fernandez, Nicolas, Gaulton, Anna, Hersey, Anne, Holmes, Jayme, Jensen, Lars Juhl, Karlsson, Anneli, Guixia Liu, Ma'ayan, Avi, Mandava, Geetha, Mani, Subramani, Mehta, Saurabh, Overington, John, Patel, Juhee, Rouillard, Andrew D., Schürer, Stephan, and Sheils, Timothy

Published
2017
Full Text
View/download PDF

28. TCRD and Pharos 2021: mining the human proteome for disease biology.

Author

Sheils TK, Mathias SL, Kelleher KJ, Siramshetty VB, Nguyen DT, Bologa CG, Jensen LJ, Vidović D, Koleti A, Schürer SC, Waller A, Yang JJ, Holmes J, Bocci G, Southall N, Dharkar P, Mathé E, Simeonov A, and Oprea TI

Subjects
Animals, Anticonvulsants chemistry, Anticonvulsants therapeutic use, Antiviral Agents chemistry, Antiviral Agents therapeutic use, Biological Products chemistry, Biological Products therapeutic use, Data Mining statistics & numerical data, Host-Pathogen Interactions drug effects, Host-Pathogen Interactions genetics, Humans, Internet, Machine Learning statistics & numerical data, Mice, Mice, Knockout, Molecular Targeted Therapy methods, Neurodegenerative Diseases classification, Neurodegenerative Diseases drug therapy, Neurodegenerative Diseases virology, Protein Interaction Mapping, Proteome agonists, Proteome antagonists & inhibitors, Proteome genetics, Proteome metabolism, Small Molecule Libraries chemistry, Small Molecule Libraries therapeutic use, Virus Diseases classification, Virus Diseases drug therapy, Virus Diseases virology, Databases, Factual, Genome, Human, Neurodegenerative Diseases genetics, Proteomics methods, Software, Virus Diseases genetics
Abstract

In 2014, the National Institutes of Health (NIH) initiated the Illuminating the Druggable Genome (IDG) program to identify and improve our understanding of poorly characterized proteins that can potentially be modulated using small molecules or biologics. Two resources produced from these efforts are: The Target Central Resource Database (TCRD) (http://juniper.health.unm.edu/tcrd/) and Pharos (https://pharos.nih.gov/), a web interface to browse the TCRD. The ultimate goal of these resources is to highlight and facilitate research into currently understudied proteins, by aggregating a multitude of data sources, and ranking targets based on the amount of data available, and presenting data in machine learning ready format. Since the 2017 release, both TCRD and Pharos have produced two major releases, which have incorporated or expanded an additional 25 data sources. Recently incorporated data types include human and viral-human protein-protein interactions, protein-disease and protein-phenotype associations, and drug-induced gene signatures, among others. These aggregated data have enabled us to generate new visualizations and content sections in Pharos, in order to empower users to find new areas of study in the druggable genome., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2021
Full Text
View/download PDF

29. DrugCentral 2021 supports drug discovery and repositioning.

Author

Avram S, Bologa CG, Holmes J, Bocci G, Wilson TB, Nguyen DT, Curpan R, Halip L, Bora A, Yang JJ, Knockel J, Sirimulla S, Ursu O, and Oprea TI

Subjects
Antiviral Agents adverse effects, Antiviral Agents pharmacokinetics, COVID-19 epidemiology, COVID-19 virology, Drug Approval methods, Drug Discovery methods, Drug Repositioning methods, Epidemics, Europe, Humans, Information Storage and Retrieval methods, Internet, Japan, SARS-CoV-2 physiology, United States, Antiviral Agents therapeutic use, Databases, Pharmaceutical statistics & numerical data, Drug Approval statistics & numerical data, Drug Discovery statistics & numerical data, Drug Repositioning statistics & numerical data, SARS-CoV-2 drug effects, COVID-19 Drug Treatment
Abstract

DrugCentral is a public resource (http://drugcentral.org) that serves the scientific community by providing up-to-date drug information, as described in previous papers. The current release includes 109 newly approved (October 2018 through March 2020) active pharmaceutical ingredients in the US, Europe, Japan and other countries; and two molecular entities (e.g. mefuparib) of interest for COVID19. New additions include a set of pharmacokinetic properties for ∼1000 drugs, and a sex-based separation of side effects, processed from FAERS (FDA Adverse Event Reporting System); as well as a drug repositioning prioritization scheme based on the market availability and intellectual property rights forFDA approved drugs. In the context of the COVID19 pandemic, we also incorporated REDIAL-2020, a machine learning platform that estimates anti-SARS-CoV-2 activities, as well as the 'drugs in news' feature offers a brief enumeration of the most interesting drugs at the present moment. The full database dump and data files are available for download from the DrugCentral web portal., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2021
Full Text
View/download PDF

30. REDIAL-2020: A suite of machine learning models to estimate Anti-SARS-CoV-2 activities.

Author

Govinda KC, Bocci G, Verma S, Hassan M, Holmes J, Yang JJ, Sirimulla S, and Oprea TI

Abstract

Strategies for drug discovery and repositioning are an urgent need with respect to COVID-19. We developed "REDIAL-2020", a suite of machine learning models for estimating small molecule activity from molecular structure, for a range of SARS-CoV-2 related assays. Each classifier is based on three distinct types of descriptors (fingerprint, physicochemical, and pharmacophore) for parallel model development. These models were trained using high throughput screening data from the NCATS COVID19 portal (https://opendata.ncats.nih.gov/covid19/index.html), with multiple categorical machine learning algorithms. The "best models" are combined in an ensemble consensus predictor that outperforms single models where external validation is available. This suite of machine learning models is available through the DrugCentral web portal (http://drugcentral.org/Redial). Acceptable input formats are: drug name, PubChem CID, or SMILES; the output is an estimate of anti-SARS-CoV-2 activities. The web application reports estimated activity across three areas ( viral entry , viral replication , and live virus infectivity ) spanning six independent models, followed by a similarity search that displays the most similar molecules to the query among experimentally determined data. The ML models have 60% to 74% external predictivity, based on three separate datasets. Complementing the NCATS COVID19 portal, REDIAL-2020 can serve as a rapid online tool for identifying active molecules for COVID-19 treatment. The source code and specific models are available through Github (https://github.com/sirimullalab/redial-2020), or via Docker Hub (https://hub.docker.com/r/sirimullalab/redial-2020) for users preferring a containerized version., Competing Interests: Conflicts of Interest T.I.O. has received honoraria or consulted for Abbott, AstraZeneca, Chiron, Genentech, Infinity Pharmaceuticals, Merz Pharmaceuticals, Merck Darmstadt, Mitsubishi Tanabe, Novartis, Ono Pharmaceuticals, Pfizer, Roche, Sanofi and Wyeth. He is on the Scientific Advisory Board of ChemDiv Inc. and InSilico Medicine.

Published
2020
Full Text
View/download PDF

31. Pharos: Collating protein information to shed light on the druggable genome.

Author

Nguyen DT, Mathias S, Bologa C, Brunak S, Fernandez N, Gaulton A, Hersey A, Holmes J, Jensen LJ, Karlsson A, Liu G, Ma'ayan A, Mandava G, Mani S, Mehta S, Overington J, Patel J, Rouillard AD, Schürer S, Sheils T, Simeonov A, Sklar LA, Southall N, Ursu O, Vidovic D, Waller A, Yang J, Jadhav A, Oprea TI, and Guha R

Subjects
Cluster Analysis, Computational Biology methods, Humans, Obesity drug therapy, Obesity genetics, Obesity metabolism, Software, Web Browser, Databases, Genetic, Drug Discovery methods, Genomics methods, Pharmacogenetics methods, Search Engine
Abstract

The 'druggable genome' encompasses several protein families, but only a subset of targets within them have attracted significant research attention and thus have information about them publicly available. The Illuminating the Druggable Genome (IDG) program was initiated in 2014, has the goal of developing experimental techniques and a Knowledge Management Center (KMC) that would collect and organize information about protein targets from four families, representing the most common druggable targets with an emphasis on understudied proteins. Here, we describe two resources developed by the KMC: the Target Central Resource Database (TCRD) which collates many heterogeneous gene/protein datasets and Pharos (https://pharos.nih.gov), a multimodal web interface that presents the data from TCRD. We briefly describe the types and sources of data considered by the KMC and then highlight features of the Pharos interface designed to enable intuitive access to the IDG knowledgebase. The aim of Pharos is to encourage 'serendipitous browsing', whereby related, relevant information is made easily discoverable. We conclude by describing two use cases that highlight the utility of Pharos and TCRD., (Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results