A Computational Framework for Genome-wide Characterization of the Human Disease Landscape.

TitleA Computational Framework for Genome-wide Characterization of the Human Disease Landscape.
Publication TypeJournal Article
Year of Publication2019
AuthorsLee, Y-S, Krishnan, A, Oughtred, R, Rust, J, Chang, CS, Ryu, J, Kristensen, VN, Dolinski, K, Theesfeld, CL, Troyanskaya, OG
JournalCell Syst
Date Published2019 Feb 27
KeywordsGene Expression Profiling, Genomics, Humans, Machine Learning, Transcriptome

<p>A key challenge for the diagnosis and treatment of complex human diseases is identifying their molecular basis. Here, we developed a unified computational framework, URSA (Unveiling RNA Sample Annotation for Human Diseases), that leverages machine learning and the hierarchy of anatomical relationships present among diseases to integrate thousands of clinical gene expression profiles and identify molecular characteristics specific to each of the hundreds of complex diseases. URSA can distinguish between closely related diseases more accurately than literature-validated genes or traditional differential-expression-based computational approaches and is applicable to any disease, including rare and understudied ones. We demonstrate the utility of URSA in classifying related nervous system cancers and experimentally verifying novel neuroblastoma-associated genes identified by URSA. We highlight the applications for potential targeted drug-repurposing and for quantitatively assessing the molecular response to clinical therapies. URSA is freely available for public use, including the use of underlying models, at ursahd.princeton.edu.</p>

Alternate JournalCell Syst
PubMed ID30685436
PubMed Central IDPMC7374759
Grant ListR01 GM071966 / GM / NIGMS NIH HHS / United States
R24 OD011194 / OD / NIH HHS / United States
/ / CIHR / Canada