DOSE-L1000: unveiling the intricate landscape of compound-induced transcriptional changes

Author:

Wang Junmin1ORCID,Novick Steven2

Affiliation:

1. Data Sciences and Quantitative Biology, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca , Gaithersburg, MD 20878, United States

2. Global Statistical Sciences, Eli Lilly , Indianapolis, IN 46285, United States

Abstract

Abstract Motivation The LINCS L1000 project has collected gene expression profiles for thousands of compounds across a wide array of concentrations, cell lines, and time points. However, conventional analysis methods often fall short in capturing the rich information encapsulated within the L1000 transcriptional dose–response data. Results We present DOSE-L1000, a database that unravels the potency and efficacy of compound-gene pairs and the intricate landscape of compound-induced transcriptional changes. Our study uses the fitting of over 140 million generalized additive models and robust linear models, spanning the complete spectrum of compounds and landmark genes within the LINCS L1000 database. This systematic approach provides quantitative insights into differential gene expression and the potency and efficacy of compound-gene pairs across diverse cellular contexts. Through examples, we showcase the application of DOSE-L1000 in tasks such as cell line and compound comparisons, along with clustering analyses and predictions of drug–target interactions. DOSE-L1000 fosters applications in drug discovery, accelerating the transition to omics-driven drug development. Availability and implementation DOSE-L1000 is publicly available at https://doi.org/10.5281/zenodo.8286375.

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

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