Biology subjects

Tosh, C.

Publications and source records attributed to Tosh, C..

5 recordsLinked to original sources

bioRxiv2026

CellConsensus: An agent-curated atlas for automatic cell typing

Assigning cell types to single-cell and spatial transcriptomic data remains inconsistent because marker gene knowledge is fragmented across thousands of individual studies. Here we present CellConsensus, a cell typing method built on a consensus corpus of marker genes aggregated from curated atlases (2,607 sources) and de novo mining of 1,174 papers. By reconciling overlapping and conflicting marker evidence into a consensus reference, CellConsensus assigns cell type labels that are more accurate and more reproducible than existing marker- and reference-based approaches, while remaining interpretable and applicable across tissues and platforms. CellConsensus is available as an open-source Python package (https://github.com/tansey-lab/cellconsensus), an interactive database (https://cellconsensus.org), and as an agentic MCP server for conversational querying.

bioinformatics↗

bioRxiv2026

A Pan-Cancer Ex Vivo Drug Screen Atlas for Functional Precision Oncology

Compared to immortalized cell lines, patient-derived organoids and other ex vivo models have been shown to better recapitulate patient responses to therapy. High cost and technical complexity have prevented the creation of pan-cancer ex vivo datasets, limiting comprehensive analyses and predictive modeling for ex vivo drug response. We present the Pan-PreClinical (PPC) project: a drug screen atlas of 2.1M experiments across 1,982 ex vivo samples and 3,100 drugs spanning 134 cancer indications tested across 26 studies. We develop a contrastive Bayesian model to harmonize across studies, identifying 303 tissue-specific drug sensitivities and demonstrating drug sensitivities are predictive of clinically-relevant molecular profiles. Integrating established cell line databases reveals systematic biases across 55 cancer subtypes, with cell line screens favoring drugs targeting highly proliferative cells and undervaluing cell-cell communication targets. We leverage PPC to establish an ex vivo foundation model and computational platform for scalable ex vivo cancer biology and predictive oncology.

cancer biology↗

bioRxiv2026

Pathology of dose dependent inocula of H5N8 avian influenza viruses in experimentally infected chicken

In the present study, we assessed the pathogenicity of H5N8 avian influenza viruses belongs to the clade 2.3.4.4b in chicken. Birds of three different dose groups, 102, 104, and 106 EID50 were used in the study. No mortality was observed in 102 EID0 group. Percent cumulative mortality of 104 and 106 EID50 group was 66.67 and 100 %, respectively. Varying duration of MDT of 3.2 and 2 days was observed in 104 and 106 EID50 group, respectively. The CID50 of virus was found to be 104.5 EID50. High no. of viral RNA copies were found both in oropharyngeal and cloacal swabs and in various organs of birds infected in 104 and 106 EID50 group. Significant gross and histological changes and presence of viral antigen in various organs were observed in 104 and 106 EID50 group. So, the study concludes that Indian HPAI, H5N8 isolates are highly pathogenic in nature to chicken by affecting most organs systemically. CID50 of this H5N8 virus indicates poor adaption in chicken and it implies poor transmission possibility of this virus for host species in field condition. Though this virus is highly pathogenic in nature as that of HPAI, H5N1 viruses, absence of endothelial staining in most organ attributes variation in replication process and pathogenesis from HPAI, H5N1 viruses. Hence, further studies need to be done to elucidate the pathobiology of this virus in various bird species. HighlightsO_LIH5N8 virus belong to the clade 2.3.4.4b, Indian isolate is highly pathogenic in nature as that of HPAIV, H5N1. C_LIO_LIThe dose inocula, 102 EID50 is noninfectious to chicken. C_LIO_LIThe dose inocula, 104 and 106 EID50 had caused significant mortality in the inoculated chicken with MDT of 2 and 3.2 days, respectively. C_LIO_LIH5N8 virus was detected with high viral titres in clocal and oral shedding and in multiple organ with the dose inocula, 104 and 106 EID50. C_LIO_LI104 and 106 EID50 of H5N8 inocula virus caused significant gross and histological changes in multiple organs and viral antigens were detected in respective organs. C_LI

microbiology↗

bioRxiv2023

A Bayesian active learning platform for scalable combination drug screens

Large-scale combination drug screens are generally considered intractable due to the immense number of possible combinations. Existing approaches use ad hoc fixed experimental designs then train machine learning models to impute novel combinations. Here we propose BATCHIE, an orthogonal approach that conducts experiments dynamically in batches. BATCHIE uses information theory and probabilistic modeling to design each batch to be maximally informative based on the results of previous experiments. On retrospective experiments from previous large-scale screens, BATCHIE designs rapidly discover highly effective and synergistic combinations. To validate BATCHIE prospectively, we conducted a combination screen on a collection of pediatric cancer cell lines using a 206 drug library. After exploring only 4% of the 1.4M possible experiments, the BATCHIE model was highly accurate at predicting novel combinations and detecting synergies. Further, the model identified a panel of top combinations for Ewing sarcomas, all of which were experimentally confirmed to be effective, including the rational and translatable top hit of PARP plus topoisomerase I inhibition. These results demonstrate that adaptive experiments can enable large-scale unbiased combination drug screens with a relatively small number of experiments, thereby powering a new wave of combination drug discoveries. BATCHIE is open source and publicly available (https://github.com/tansey-lab/batchie).

bioinformatics↗

bioRxiv2023

Unraveling molecular basis for reduced neuraminidase inhibitors susceptibility in highly pathogenic avian influenza A (H5N1) viruses isolated from chickens in India

The increasing resistance cases in influenza viruses to different classes of antiviral drugs, necessitates the in-depth analysis of molecular interactions governing reduced susceptibility to these drugs. This study explores the molecular basis of neuraminidase inhibitors resistance in avian H5N1 influenza viruses identified in our previous research. Using comprehensive modeling and docking tools, we investigated two isolates--A/chicken/India/85459/2008 (N294S) and A/chicken/WestBengal/142121/2008 (E119A + I117V). The N294S mutation conferred oseltamivir resistance while retaining zanamivir susceptibility, whereas the E119A + I117V mutations led to zanamivir resistance while reducing oseltamivir susceptibility. Molecular interactions analysis unveiled varied fitness levels, hydrogen bonding, and affinity transitions associated with N294S and E119A + I117V mutations. This study provides crucial insights into molecular interactions responsible for reduced susceptibility to neuraminidase inhibitors, which is essential for optimizing antiviral strategies and pandemic preparedness.

microbiology↗