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Biology subjects

Combs, S.

Publications and source records attributed to Combs, S..

2 recordsLinked to original sources

Bridging biomolecular modalities for knowledge transfer in bio-language models

In biology, messenger RNA (mRNA) plays a crucial role in gene expression and protein synthesis. Accurate predictive modeling of mRNA properties can greatly enhance our understanding and manipulation of biological processes, leading to advancements in medical and biotechnological applications. Utilizing bio-language foundation models allows for leveraging large-scale pretrained knowledge, which can significantly improve the efficiency and accuracy of these predictions. However, mRNA specific foundation models are notably limited posing challenges for efficient predictive modeling in mRNA-focused tasks. In contrast, DNA and protein modalities have numerous general-purpose foundation models trained on billions of sequences. This paper explores the potential for adaptation of existing DNA and protein bio-language models for mRNA-focused tasks. Through experiments using various mRNA datasets curated from both public domain and internal proprietary database, we demonstrate that pre-trained DNA and protein models can be effectively transferred for mRNA-focused tasks using various adaptation techniques such as probing, full-rank, and low-rank finetuning. In addition, we identify key factors that influence successful adaptation, offering guidelines on when general-purpose DNA and protein models are likely to perform well for mRNA-focused tasks. We further assess the impact of model size on adaptation efficacy, finding that medium-scale models often outperform larger ones for cross-modal knowledge transfer. We conclude that by leveraging the interconnectedness of DNA, mRNA, and proteins, as outlined by the central dogma of molecular biology, the knowledge in foundation models can be effectively transferred across modalities, significantly enhancing the repertoire of computational tools available for mRNA analysis.

bioinformatics↗

A tryptophan metabolite modulates the host response to bacterial infection via kainate receptors

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxy-kynurenine protects from lethal gram-negative bacterial infection. 3-hydroxy-kynurenine, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages by targeting kainate-sensitive glutamate receptors. These findings reveal new mechanisms by which tryptophan metabolism and kainate-sensitive glutamate receptors function and interact to modulate immunity, with significant implications for the coordination between the immune and nervous systems in pathological conditions.

immunology↗