Search bioRxiv⌕ Search

Biology subjects

Tubbs, A.

Publications and source records attributed to Tubbs, A..

2 recordsLinked to original sources

Using semantic search to find publicly available gene-expression datasets

Millions of high-throughput, molecular datasets have been shared in public repositories. have been shared in public repositories. Researchers can reuse such data to validate their own findings and explore novel questions. A frequent goal is to find multiple datasets that address similar research topics and to either combine them directly or integrate inferences from them. However, a major challenge is finding relevant datasets due to the vast number of candidates, inconsistencies in their descriptions, and a lack of semantic annotations. This challenge is first among the FAIR principles for scientific data. Here we focus on dataset discovery within Gene Expression Omnibus (GEO), a repository containing 100,000s of data series. GEO supports queries based on keywords, ontology terms, and other annotations. However, reviewing these results is time-consuming and tedious, and it often misses relevant datasets. We hypothesized that language models could address this problem by summarizing dataset descriptions as numeric representations (embeddings). Assuming a researcher has previously found some relevant datasets, we evaluated the potential to find additional relevant datasets. For six human medical conditions, we used 30 models to generate embeddings for datasets that human curators had previously associated with the conditions and identified other datasets with the most similar descriptions. This approach was often, but not always, more effective than GEOs search engine. Our top-performing models were trained on general corpora, used contrastive-learning strategies, and used relatively large embeddings. Our findings suggest that language models have the potential to improve dataset discovery, perhaps in combination with existing search tools.

genomics↗

LIN37-DREAM Prevents DNA End Resection and Homologous Recombination at DNA Double Strand Breaks in Quiescent Cells

DNA double strand break (DSB) repair by homologous recombination (HR) is thought to be restricted to the S- and G2- phases of the cell cycle in part due to 53BP1 antagonizing DNA end resection in G1-phase and non-cycling quiescent (G0) cells. Here, we show that LIN37, a component of the DREAM transcriptional repressor, functions in a 53BP1-independent manner to prevent DNA end resection and HR in G0 cells. Loss of LIN37 leads to expression of HR proteins, including BRCA1, BRCA2, PALB2 and RAD51, and DNA end resection in G0 cells even in the presence of 53BP1. In contrast to 53BP1-deficiency, DNA end resection in LIN37-deficient G0 cells depends on BRCA1 and leads to RAD51 filament formation and HR. LIN37 is not required to protect DNA ends in cycling cells at G1-phase. Thus, LIN37 regulates a novel 53BP1-independent cell phase-specific DNA end protection pathway that functions uniquely in quiescent cells.

cell biology↗