Dataset Information

StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit.

ABSTRACT: Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods for generating datasets such as genomics, phenomics, and proteomics, attempts to integrate and mine such datasets remain limited in scope. Developing hybrid intelligence solutions that combine human intelligence in the scientific domain and disease biology with the ability to mine multiple databases simultaneously may help augment drug target discovery and identify novel drug-indication associations. We believe that integrating different data sources using a singular numerical scoring system in a hybrid intelligent framework could help to bridge these different omics layers and facilitate rapid drug target prioritization for studies in drug discovery, development or repositioning. Herein, we describe our prototype of the StarGazer pipeline which combines multi-source, multi-omics data with a novel target prioritization scoring system in an interactive Python-based Streamlit dashboard. StarGazer displays target prioritization scores for genes associated with 1844 phenotypic traits, and is available via https://github.com/AstraZeneca/StarGazer.

SUBMITTER: Lee C

PROVIDER: S-EPMC9197487 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit.

Lee Chiyun C Lin Junxia J Prokop Andrzej A Gopalakrishnan Vancheswaran V Hanna Richard N RN Papa Eliseo E Freeman Adrian A Patel Saleha S Yu Wen W Huhn Monika M Sheikh Abdul-Saboor AS Tan Keith K Sellman Bret R BR Cohen Taylor T Mangion Jonathan J Khan Faisal M FM Gusev Yuriy Y Shameer Khader K

Frontiers in genetics 20220531

Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods for generating datasets such as genomics, phenomics, and proteomics, attempts to integrate and mine such datasets remain limited in scope. Developing hybrid intelligence solutions that combine human intelligence in the scientific domain and diseas ...[more]

PMID: 35711912

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Project description:In diseases such as cancer, the design of new therapeutic strategies requires extensive, costly, and unfortunately sometimes deadly testing to reveal life threatening "off target" effects. A crucial first step in predicting toxicity are analyses of normal RNA and protein tissue expression, which are now possible using comprehensive molecular tissue atlases. However, no standardized approaches exist for target prioritization, which instead rely on ad-hoc thresholds and manual inspection. Such issues are compounded, given that genomic and proteomic data detection sensitivity and accuracy are often problematic. Thus, quantifiable probabilistic scores for tumor specificity that address these challenges could enable the creation of new predictive models for combinatorial drug design and correlative analyses. Here, we propose a Bayesian Tumor Specificity (BayesTS) score that can naturally account for multiple independent forms of molecular evidence derving from both RNA-Seq and protein expression while preserving the uncertainty of the inference. We applied BayesTS to 24,905 human protein-coding genes across 3,644 normal samples (GTEx and TCGA) spanning 63 tissues. These analyses demonstrate the ability of BayesTS to accurately incorporate protein, RNA and tissue distribution evidence, while effectively capturing the uncertainty of these inferences. This approach prioritized well-established drug targets, while deemphasizing those which were later found to induce toxicity. BayesTS allows for the adjustment of tissue importance weights for tissues of interest, such as reproductive and physiologically dispensable tissues (e.g., tonsil, appendix), enabling clinically translatable prioritizations. Our results show that BayesTS can facilitate novel drug target discovery and can be easily generalized to unconventional molecular targets, such as splicing neoantigens. We provide the code and inferred tumor specificity predictions as a database available online (https://github.com/frankligy/BayesTS). We envision that the widespread adoption of BayesTS will facilitate improved target prioritization for oncology drug development, ultimately leading to the discovery of more effective and safer drugs.

Dataset Information

StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit.

Publications

StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit.

Similar Datasets

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