Gene and drug landing page aggregator.

Motivation: Many biological and biomedical researchers commonly search for information about genes and drugs to gather knowledge from these resources. For the most part, such information is served as landing pages in disparate data repositories and web portals. Results: The Gene and Drug Landing Page Aggregator (GDLPA) provides users with access to 50 gene-centric and 19 drug-centric repositories, enabling them to retrieve landing pages corresponding to their gene and drug queries. Bringing these resources together into one dashboard that directs users to the landing pages across many resources can help centralize gene- and drug-centric knowledge, as well as raise awareness of available resources that may be missed when using standard search engines. To demonstrate the utility of GDLPA, case studies for the gene klotho and the drug remdesivir were developed. The first case study highlights the potential role of klotho as a drug target for aging and kidney disease, while the second study gathers knowledge regarding approval, usage, and safety for remdesivir, the first approved coronavirus disease 2019 therapeutic. Finally, based on our experience, we provide guidelines for developing effective landing pages for genes and drugs. Availability and implementation: GDLPA is open source and is available from: https://cfde-gene-pages.cloud/. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Getting Started with the IDG KMC Datasets and Tools.

The Illuminating the Druggable Genome (IDG) consortium is a National Institutes of Health (NIH) Common Fund program designed to enhance our knowledge of under-studied proteins, more specifically, proteins unannotated within the three most commonly drug-targeted protein families: G-protein coupled receptors, ion channels, and protein kinases. Since 2014, the IDG Knowledge Management Center (IDG-KMC) has generated several open-access datasets and resources that jointly serve as a highly translational machine-learning-ready knowledgebase focused on human protein-coding genes and their products. The goal of the IDG-KMC is to develop comprehensive integrated knowledge for the druggable genome to illuminate the uncharacterized or poorly annotated portion of the druggable genome. The tools derived from the IDG-KMC provide either user-friendly visualizations or ways to impute the knowledge about potential targets using machine learning strategies. In the following protocols, we describe how to use each web-based tool to accelerate illumination in under-studied proteins. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Interacting with the Pharos user interface Basic Protocol 2: Accessing the data in Harmonizome Basic Protocol 3: The ARCHS4 resource Basic Protocol 4: Making predictions about gene function with PrismExp Basic Protocol 5: Using Geneshot to illuminate knowledge about under-studied targets Basic Protocol 6: Exploring under-studied targets with TIN-X Basic Protocol 7: Interacting with the DrugCentral user interface Basic Protocol 8: Estimating Anti-SARS-CoV-2 activities with DrugCentral REDIAL-2020 Basic Protocol 9: Drug Set Enrichment Analysis using Drugmonizome Basic Protocol 10: The Drugmonizome-ML Appyter Basic Protocol 11: The Harmonizome-ML Appyter Basic Protocol 12: GWAS target illumination with TIGA Basic Protocol 13: Prioritizing kinases for lists of proteins and phosphoproteins with KEA3 Basic Protocol 14: Converting PubMed searches to drug sets with the DrugShot Appyter.

Drugmonizome and Drugmonizome-ML: integration and abstraction of small molecule attributes for drug enrichment analysis and machine learning.

Understanding the underlying molecular and structural similarities between seemingly heterogeneous sets of drugs can aid in identifying drug repurposing opportunities and assist in the discovery of novel properties of preclinical small molecules. A wealth of information about drug and small molecule structure, targets, indications and side effects; induced gene expression signatures; and other attributes are publicly available through web-based tools, databases and repositories. By processing, abstracting and aggregating information from these resources into drug set libraries, knowledge about novel properties of drugs and small molecules can be systematically imputed with machine learning. In addition, drug set libraries can be used as the underlying database for drug set enrichment analysis. Here, we present Drugmonizome, a database with a search engine for querying annotated sets of drugs and small molecules for performing drug set enrichment analysis. Utilizing the data within Drugmonizome, we also developed Drugmonizome-ML. Drugmonizome-ML enables users to construct customized machine learning pipelines using the drug set libraries from Drugmonizome. To demonstrate the utility of Drugmonizome, drug sets from 12 independent SARS-CoV-2 in vitro screens were subjected to consensus enrichment analysis. Despite the low overlap among these 12 independent in vitro screens, we identified common biological processes critical for blocking viral replication. To demonstrate Drugmonizome-ML, we constructed a machine learning pipeline to predict whether approved and preclinical drugs may induce peripheral neuropathy as a potential side effect. Overall, the Drugmonizome and Drugmonizome-ML resources provide rich and diverse knowledge about drugs and small molecules for direct systems pharmacology applications. Database URL: https://maayanlab.cloud/drugmonizome/.

The COVID-19 Drug and Gene Set Library.

In a short period, many research publications that report sets of experimentally validated drugs as potential COVID-19 therapies have emerged. To organize this accumulating knowledge, we developed the COVID-19 Drug and Gene Set Library (https://amp.pharm.mssm.edu/covid19/), a collection of drug and gene sets related to COVID-19 research from multiple sources. The platform enables users to view, download, analyze, visualize, and contribute drug and gene sets related to COVID-19 research. To evaluate the content of the library, we compared the results from six in vitro drug screens for COVID-19 repurposing candidates. Surprisingly, we observe low overlap across screens while highlighting overlapping candidates that should receive more attention as potential therapeutics for COVID-19. Overall, the COVID-19 Drug and Gene Set Library can be used to identify community consensus, make researchers and clinicians aware of new potential therapies, enable machine-learning applications, and facilitate the research community to work together toward a cure.

The COVID-19 Gene and Drug Set Library.

The coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 (COVID-19) pandemic has received rapid response by the research community to offer suggestions for repurposing of approved drugs as well as to improve our understanding of the COVID-19 viral life cycle molecular mechanisms. In a short period, tens of thousands of research preprints and other publications have emerged including those that report lists of experimentally validated drugs and compounds as potential COVID-19 therapies. In addition, gene sets from interacting COVID-19 virus-host proteins and differentially expressed genes when comparing infected to uninfected cells are being published at a fast rate. To organize this rapidly accumulating knowledge, we developed the COVID-19 Gene and Drug Set Library (https://amp.pharm.mssm.edu/covid19/), a collection of gene and drug sets related to COVID-19 research from multiple sources. The COVID-19 Gene and Drug Set Library is delivered as a web-based interface that enables users to view, download, analyze, visualize, and contribute gene and drug sets related to COVID-19 research. To evaluate the content of the library, we performed several analyses including comparing the results from 6 in-vitro drug screens for COVID-19 repurposing candidates. Surprisingly, we observe little overlap across these initial screens. The most common and unique hit across these screen is mefloquine, a malaria drug that should receive more attention as a potential therapeutic for COVID-19. Overall, the library of gene and drug sets can be used to identify community consensus, make researchers and clinicians aware of the development of new potential therapies, as well as allow the research community to work together towards a cure for COVID-19.