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Jatav, S.

Publications and source records attributed to Jatav, S..

4 recordsLinked to original sources

DEEPGEOSEARCH: LLM-POWERED SCHEMALESS RETRIEVALFOR BIOMEDICAL DATA DISCOVERY

Public biomedical repositories contain extensive, valuable datasets, yet identifying datasets that precisely match specific study requirements remains inefficient. Conventional keyword- and schema-based systems frequently fall short when queries encompass multiple biological and experimental facets. To address this, we developed DeepGEOSearch, an LLM-powered, schema-less retrieval system that interprets dataset text directly rather than relying solely on predefined metadata fields. The system extracts key study attributes, harmonizes terminology across sources, and ranks datasets by contextual alignment with natural-language queries while providing verifiable evidence for each match. In this work, we applied DeepGEOSearch for the Gene Expression Omnibus (GEO). The framework is repository-agnostic and can integrate new metadata sources without manual relabeling. This design enables complex compositional queries that existing tools cannot support. In evaluations against strong baselines using a curated evaluation benchmark comprising a mix of query complexities, DeepGEOSearch achieved more than 90% precision and best recall, with the largest performance gains observed on complex, real-world queries. DeepGEOSearch consistently identifies relevant datasets overlooked by conventional search tools, accelerating dataset discovery and improving reuse of public biomedical data.

bioinformatics↗

Beyond the Hype: The Complexity of Automated Cell Type Annotations with GPT-4

Recent research has shown the impressive capability of large language models like GPT-4 in various downstream tasks in single-cell data analysis. Among these tasks, cell type annotation remains particularly challenging, with researchers exploring various methods to improve accuracy and efficiency. While recent studies on GPT-like models have demonstrated annotation performance comparable to manual annotations, a significant gap remains in understanding their limitations and generalizability. In this work, we compare and evaluate the annotation performance of the GPT-4 model against traditional methods on nine randomly selected public single-cell RNA seq datasets from cellxgene, covering diverse tissue types. Our evaluation highlights the complexity of annotating cell types in single-cell data, revealing key differences between automated and manual approaches. We found specific cases where GPT-4 underperforms, demonstrating its limitations in certain contexts. We further introduce an automated approach to incorporate literature search using a RAG approach which enhances and outperforms GPT-4 cell type annotation when compared to traditional methods. We also introduce metrics based on taxonomic distance in the ontology tree to evaluate the granularity of the cell type annotations. To support future research, we also release an open-source Python package 1 that enables fully automated cell-type annotation of single-cell data using GPT-4 alongside other methods. The pipeline can take paper as an input and do cell type annotations on its own.

bioinformatics↗

Inferring metabolic rewiring in embryonic neural development using single cell data

Metabolism is intricately linked with cell fate changes. Much of this understanding comes from detailed metabolomics studies averaged across a population of cells which may be composed of multiple cell types. Currently, there are no quantitative techniques sensitive enough to assess metabolomics broadly at the single cell level. Here we present scMetNet, a technique that interrogates metabolic rewiring at the single cell resolution and we apply it to murine embryonic development. Our method first confirms the key metabolic pathways, categorized into bioenergetic, epigenetic and biosynthetic, that change as embryonic neural stem cells differentiate and age. It then goes beyond to identify specific sub-networks, such as the cholesterol and mevalonate biosynthesis pathway, that drive the global metabolic changes during neural cortical development. Having such contextual information about metabolic rewiring provides putative mechanisms driving stem cell differentiation and identifies potential targets for regulating neural stem cell and neuronal biology.

systems biology↗

Integrated Metabolomic and Transcriptomic Profiling Reveals Novel Activation-Induced Metabolic Networks in Human T cells

The targeting of metabolic pathways is emerging as an exciting new approach for modulating immune cell function and polarization states. In this study, carbon tracing and systems biology approaches integrating metabolomic and transcriptomic profiling data were used to identify adaptations in human T cell metabolism important for fueling pro-inflammatory T cell function. Results of this study demonstrate that T cell receptor (TCR) stimulation leads to a significant increase in glucose and amino acid metabolism that trigger downstream biosynthetic processes. Specifically, increased expression of several enzymes such as CTPS1, IL4I1, and ASL results in the reprogramming of amino acid metabolism. Additionally, the strength of TCR signaling resulted in different metabolic enzymes utilized by T cells to facilitate similar biochemical endpoints. Furthermore, this study shows that cyclosporine represses the pathways involved in amino acid and glucose metabolism, providing novel insights on the immunosuppressive mechanisms of this drug. To explore the implications of the findings of this study in clinical settings, conventional immunosuppressants were tested in combination with drugs that target metabolic pathways. Results showed that such combinations increased efficacy of conventional immunosuppressants. Overall, the results of this study provide a comprehensive resource for identifying metabolic targets for novel combinatorial regimens in the treatment of intractable immune diseases.

immunology↗