Biology subjects

Tully, B.

Publications and source records attributed to Tully, B..

4 recordsLinked to original sources

bioRxiv2022

Pan-cancer proteomic map of 949 human cell lines reveals principles of cancer vulnerabilities

The proteome provides unique insights into biology and disease beyond the genome and transcriptome. Lack of large proteomic datasets has restricted identification of new cancer biomarkers. Here, proteomes of 949 cancer cell lines across 28 tissue types were analyzed by mass spectrometry. Deploying a clinically-relevant workflow to quantify 8,498 proteins, these data capture evidence of cell type and post-transcriptional modifications. Integrating multi-omics, drug response and CRISPR-Cas9 gene essentiality screens with a deep learning-based pipeline revealed thousands of protein-specific biomarkers of cancer vulnerabilities. Proteomic data had greater power to predict drug response than the equivalent portion of the transcriptome. Further, random downsampling to only 1,500 proteins had limited impact on predictive power, consistent with protein networks being highly connected and co-regulated. This pan-cancer proteomic map (ProCan-DepMapSanger), available at https://cellmodelpassports.sanger.ac.uk, is a comprehensive resource revealing principles of protein regulation with important implications for future clinical studies.

systems biology↗

bioRxiv2019

Toffee - a highly efficient, lossless file format for DIA-MS

The closed nature of vendor file formats in mass spectrometry is a significant barrier to progress in developing robust bioinformatics software. In response, the community has developed the open mzML format, implemented in XML and based on controlled vocabularies. Widely adopted, mzML is an important step forward; however, it suffers from two challenges that are particularly apparent as the field moves to high-throughput proteomics: large increase in file size, and a largely sequential I/O access pattern. Described here is toffee, an open, random I/O format backed by HDF5, with lossless compression that gives file sizes similar to the original vendor format and can be reconverted back to mzML without penalty. It is shown that mzML and toffee are equivalent when processing data using OpenSWATH algorithms, in additional to novel applications that are enabled by new data access patterns. For instance, a peptide-centric deep-learning pipeline for peptide identification is proposed. Documentation and examples are available at https://toffee.readthedocs.io, and all code is MIT licensed at https://bitbucket.org/cmriprocan/toffee.

bioinformatics↗

bioRxiv2017

A dynamic microbial community with high functional redundancy inhabits the cold, oxic subseafloor aquifer

The rock-hosted subseafloor crustal aquifer harbors a reservoir of microbial life that may influence global marine biogeochemical cycles. Here we utilized genomic reconstruction of crustal fluid samples from North Pond, located on the flanks of the Mid-Atlantic Ridge, a site with cold, oxic subseafloor fluid circulation within the upper basement. Twenty-one samples were collected during a two-year period at three different depths and two locations with the basaltic aquifer to examine potential microbial metabolism and community dynamics. We observed minor changes in the geochemical signatures over the two years, yet a dynamic microbial community was present in the crustal fluids that underwent large shifts in the dominant taxonomic groups. An analysis of 195 metagenome-assembled genomes (MAGs) were generated from the dataset and revealed a connection between litho- and autotrophic processes, linking carbon fixation to the oxidation of sulfide, sulfur, thiosulfate, hydrogen, and ferrous iron in a diverse group of microorganisms. Despite oxic conditions, analysis of the MAGs indicated that members of the microbial community were poised to exploit hypoxic or anoxic conditions through the use of microaerobic cytochromes and alternative electron acceptors. Temporal and spatial trends from the MAGs revealed a high degree of functional redundancy that did not correlate with the shifting microbial community membership, suggesting functional stability in mediating subseafloor biogeochemical cycles.

microbiology↗

bioRxiv2017

Undocumented Potential For Primary Productivity In A Globally-Distributed Bacterial Photoautotroph

Aerobic anoxygenic phototrophs (AAnPs) are common in the global oceans and are associated with photoheterotrophic activity. To date, AAnPs have not been identified in the surface ocean that possess the potential for carbon fixation. Using the Tara Oceans metagenomic dataset, we have reconstructed draft genomes of four bacteria that possess the genomic potential for anoxygenic phototrophy, carbon fixation via the Calvin-Benson-Bassham cycle, and the oxidation of sulfite and thiosulfate. Forming a monophyletic clade within the Alphaproteobacteria and lacking cultured representatives, the organisms compose minor constituents of local microbial communities (0.1-1.0%), but are globally distributed, present in multiple samples from the North Pacific, Mediterranean Sea, the East Africa Coastal Province, and the South Atlantic. These organisms represent a shift in our understanding of microbially-mediated photoautotrophy in the global oceans and provide a previously undiscovered route of primary productivity.\n\nSignificance StatementIn examining the genomic content of organisms collected during the Tara Oceans expedition, we have identified a novel clade within the Alphaproteobacteria that has the potential for photoautotrophy. Based on genome observations, these organisms have the potential to couple inorganic sulfur compounds as electron donors to fix carbon into biomass. They are globally distributed, present in samples from the North Pacific, Mediterranean Sea, East Africa Coastal Current, and the South Atlantic. This discovery may require re-examination of the microbial communities in the global ocean to understand and constrain the impacts of this group of organisms on the global carbon cycle.

microbiology↗