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Biology subjects

Feldman, S.

Publications and source records attributed to Feldman, S..

3 recordsLinked to original sources

Scientific computing in the age of agentic AI: an exploratory field report

Scientific computing has become a central component of modern scientific discovery. Yet many computational tools are developed by small, specialized teams under incentives that encourage the release of rapidly prototyped tooling without commensurate attention to engineering concerns, including performance and maintainability. These gaps are particularly visible in the life sciences, where the advent of high-throughput sequencing and molecular profiling has made the production and processing of datasets routine at scales that strain reliability and cost. Recently, LLM-based agents have become increasingly capable, with publicly available systems possessing both significant domain knowledge in many scientific fields and the ability to autonomously operate over complex and specialized codebases in pursuit of well-defined goals. Together, these developments create a practical opportunity for scientific computing. Many of the persistent weaknesses of the scientific computing ecosystem stem from technical debt and a shortage of sustained engineering labor and expertise. Here, we examine coding agents as a potential way to address these weaknesses: we present an exploratory field report of eight early case studies in the application of LLM agents to scientific computing across a range of project scopes, from lightweight maintenance tasks to full performance-oriented rewrites of scientific libraries, with a focus on the life sciences. Each of these case studies is accompanied by reflections from the individual or group responsible for the work, including lessons from the process. Overall, we find that the use of coding agents in scientific computing holds great promise for accelerating scientific research and increasing the reliability of critical systems, but that outstanding concerns remain, including responsibility and ownership for such projects, and we suggest collaboration and stewardship with existing maintainers when feasible.

bioinformatics↗

Rapid emergence of extensively drug-resistant Shigella sonnei in France

Shigella sonnei, the main cause of bacillary dysentery in high-income countries, has become increasingly resistant to antibiotics. We monitored the antimicrobial susceptibility of 7,121 S. sonnei isolates collected in France between 2005 and 2021. We identified a dramatic increase in the proportion of extensively drug-resistant (XDR) isolates (i.e., simultaneously resistant to ciprofloxacin, third-generation cephalosporins and azithromycin), to 22.3% of all S. sonnei isolates in 2021. Our genomic analysis identified 13 different clusters of XDR isolates descended from a ciprofloxacin-resistant sublineage originating from South Asia. The 164 XDR isolates detected were resistant to azithromycin, principally through a pKSR100-like plasmid, and to third-generation cephalosporins through various genes and plasmids. This rapid emergence of XDR S. sonnei in different transmission networks, particularly among men who have sex with men, is a matter of concern, and good laboratory-based surveillance of Shigella infections will be crucial for informed decision-making and appropriate public health action.

microbiology↗

Esrrb is a cell cycle dependent priming factor balancing between pluripotency and differentiation

Cell cycle and differentiation decisions are tightly linked; however, the underlying principles that drive these decisions are not fully understood. Here, we combined cell-cycle reporter system and single-cell RNA-seq profiling to study the transcriptomes of mouse embryonic stem cells (ESCs) in the context of cell cycle states and differentiation. By applying retinoic acid, a multi-linage differentiation assay, on G1 and G2/M pre-sorted ESCs, we show that only G2/M ESCs were capable of differentiating into extraembryonic endoderm cells (XENs), whereas cells in the G1 phase predominantly produce Epiblast Stem Cells. We identified ESRRB, a key pluripotency factor that is upregulated during G2/M phase, as a central driver of XEN differentiation. Furthermore, enhancer chromatin states based on WT and Esrrb-KO ESCs show association of ESRRB with XEN poised enhancers. Cells engineered to overexpress Esrrb during G1 allow ESCs to produce XENs, while ESRRB-KO ESCs lost their potential to differentiate into XEN. In addition, Embryonic bodies (EBs) are not affected by deletion of ESRRB but trigger apoptosis upon attempts to apply direct XEN differentiation. Taken together, this study reveals an important functional link between Esrrb and cell-cycle states during the exit from pluripotency. Finally, the experimental scheme of single cell RNA-seq in the context of cell cycle can be further expanded into other cellular systems to better understand differentiation decisions and cancer models.

genomics↗