bioRxiv Science⌕ Search

Biology subjects

Deolankar, S.

Publications and source records attributed to Deolankar, S..

2 recordsLinked to original sources

Correlate: A Web Application for Analyzing Gene Sets and Exploring Gene Dependencies Using CRISPR Screen Data

CRISPR screen data provides a valuable resource for understanding gene function and identifying potential drug targets. Here, we present Correlate, a freely accessible web application (https://correlate.cmm.se) that enables exploration of the Cancer Dependency Map (DepMap) CRISPR screen gene effects, hotspot mutations, and translocation/fusion data across more than 1,000 human cancer cell lines. The application supports two main use cases: (i) analysis of user-defined gene sets (e.g. CRISPR screen hits) to identify functionally linked genes based on correlations while providing an overview based on essentiality or user-provided screen statistics; and (ii) exploration of genes of interest in defined biological contexts, such as specific cancer types or mutational backgrounds, to generate hypotheses about gene function and dependencies. Additionally, Correlate supports experimental design by providing rapid overviews of gene essentiality and enabling the identification of cell lines with relevant mutational profiles. In contrast to knowledge-based approaches such as STRING and GSEA, which rely on prior biological annotations and curated interaction networks, Correlate identifies gene connections directly from functional CRISPR screen readouts, offering a complementary and data-driven perspective on gene network analysis. The application runs entirely in the browser, requires no installation or login, and integrates with the Green Listed v2.0 tool family for custom CRISPR screen design. HIGHLIGHTS{blacksquare} Interactive web-based platform for bulk correlation analysis of user-defined gene sets using DepMap CRISPR screen data, requiring no installation or programming expertise. {blacksquare}Identifies functional gene relationships from CRISPR screen readouts rather than curated annotations, offering a data-driven complement to tools such as GSEA and STRING. {blacksquare}Enables contextual exploration of gene dependencies across cancer types and mutational backgrounds, supporting hypothesis generation about gene function and therapeutic targets. {blacksquare}Supports experimental design through gene essentiality overviews, mutation and fusion analysis, and cell line identification, with optional integration of user-provided statistics from CRISPR screens, proteomics, or transcriptomics analyses.

bioinformatics↗

Proteostasis modulates gene dosage evolution in antibiotic-resistant bacteria

Evolution of gene expression frequently drives antibiotic resistance in bacteria. We had previously (Patel and Matange, eLife, 2021) shown that, in Escherichia coli, mutations at the mgrB locus were beneficial under trimethoprim exposure and led to overexpression of dihydrofolate reductase (DHFR), encoded by the folA gene. Here, we show that DHFR levels are further enhanced by spontaneous duplication of a genomic segment encompassing folA and spanning hundreds of kilobases. This duplication was rare in wild type E. coli. However, its frequency was elevated in a lon-knockout strain, altering the mutational landscape early during trimethoprim adaptation. We then exploit this system to investigate the relationship between trimethoprim pressure and folA copy number. During long-term evolution, folA duplications were frequently reversed. Reversal was slower under antibiotic pressure, first requiring the acquisition of point mutations in DHFR or its promoter. Unexpectedly, despite resistance-conferring point mutations, some populations under high trimethoprim pressure maintained folA duplication to compensate for low abundance DHFR mutants. We find that evolution of gene dosage depends on expression demand, which is generated by antibiotic and exacerbated by proteolysis of drug-resistant mutants of DHFR. We propose a novel role for proteostasis as a determinant of copy number evolution in antibiotic-resistant bacteria.

genetics↗