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Espinosa-Carrasco, J.

Publications and source records attributed to Espinosa-Carrasco, J..

2 recordsLinked to original sources

An nf-core framework for the systematic comparison of alternative modeling tools: the multiple sequence alignment case study

The computational complexity of many key bioinformatics problems has resulted in numerous alternative heuristic solutions, where no single approach consistently outperforms all others. This creates difficulties for users trying to identify the most suitable tool for their dataset and for developers managing and evaluating alternative methods. As data volumes grow, deploying these methods becomes increasingly difficult, highlighting the need for standardized frameworks for seamless tool deployment and comparison in HPC environments. Multiple sequence aligners (MSAs) rank among the most commonly employed modeling techniques in bioinformatics, playing a crucial role in applications such as protein structure prediction, phylogenetic reconstruction, and variant effect prediction. The NP-hardness of MSAs makes them a major example of problems where heuristics stand central, as no optimal solution can be currently obtained, within the limits of operational computational requirements. Here, we present a pilot design of an nf-core framework for streamlined tool deployment and rigorous performance evaluation focusing on the MSAs software ecosystem. By integrating the most popular MSA tools and focusing on a modular, and extensible architecture, we aspire to provide a key platform supporting MSA deployment, evaluation, and algorithmics development to the MSA community, and a proof-of-principle to the wider bioinformatics community.

bioinformatics↗

Loss of HMCES is synthetic lethal with APOBEC activity in cancer cells

Analysis of cancer mutagenic signatures provides information about the origin of mutations and can inform the use of clinical therapies, including immunotherapy. In particular, APOBEC3A (A3A) has emerged as a major driver of mutagenesis in cancer cells and its expression results in DNA damage and susceptibility to treatment with inhibitors of the ATR and CHK1 checkpoint kinases. Here we report the implementation of CRISPR/Cas9 genetic screening to identify susceptibilities of multiple A3A-expressing lung adenocarcinoma cell lines. We identify HMCES, a protein recently linked to the protection of abasic sites, as a central protein for the tolerance of A3A expression. HMCES depletion results in synthetic lethality with A3A expression specifically in a TP53-mutant background. Analysis of previous screening data reveals a strong association between A3A mutational signatures and sensitivity to HMCES loss and indicates that HMCES is specialized in protecting against a narrow spectrum of DNA damaging agents in addition to A3A. We experimentally show that both HMCES disruption and A3A expression increase susceptibility of cancer cells to ionizing radiation, oxidative stress and ATR inhibition; strategies that are often applied in tumor therapies. Overall, our results suggest that HMCES is an attractive target for selective treatment of A3A expressing tumors.

cancer biology↗