Biology subjects

Deshpande, V.

Publications and source records attributed to Deshpande, V..

21 records · Page 2Linked to original sources

bioRxiv2019

ExpansionHunter: A sequence-graph based tool to analyze variation in short tandem repeat regions

We describe a novel computational method for genotyping repeats using sequence graphs. This method addresses the long-standing need to accurately genotype medically important loci containing repeats adjacent to other variants or imperfect DNA repeats such as polyalanine repeats. Here we introduce a new version of our repeat genotyping software, ExpansionHunter, that uses this method to perform targeted genotyping of a broad class of such loci.\n\nAvailability and implementationExpansionHunter is implemented in C++ and is available under the Apache License Version 2.0. The source code, documentation, and Linux/macOS binaries are available at https://github.com/Illumina/ExpansionHunter/.\n\nContactmeberle@illumina.com

bioinformatics↗

bioRxiv2018

Entropic forces drive cellular contact guidance

Contact guidance--the widely-known phenomenon of cell alignment induced by anisotropic environmental features--is an essential step in the organization of adherent cells, but the mechanisms by which cells achieve this orientational ordering remain unclear. Here we seeded myofibroblasts on substrates micropatterned with stripes of fibronectin and observed that contact guidance emerges at stripe widths much greater than the cell size. To understand the origins of this surprising observation, we combined morphometric analysis of cells and their subcellular components with a novel statistical framework for modelling non-thermal fluctuations of living cells. This modelling framework is shown to predict not only the trends but also the statistical variability of a wide range of biological observables including cell (and nucleus) shapes, sizes and orientations, as well as stress-fibre arrangements within the cells with remarkable fidelity. By comparing observations and theory, we identified two regimes of contact guidance: (i) guidance on stripe widths smaller than the cell size (w [≤] 160 m), which is accompanied by biochemical changes within the cells, including increasing stress-fibre polarisation and cell elongation, and (ii) entropic guidance on larger stripe widths, which is governed by fluctuations in the cell morphology. Overall, our findings suggest an entropy-mediated mechanism for contact guidance associated with the tendency of cells to maximise their morphological entropy through shape fluctuations.

biophysics↗

bioRxiv2018

Reconstructing and characterizing focal amplifications in cancer using AmpliconArchitect

Focal oncogene amplification and rearrangements drive tumor growth and evolution in multiple cancer types. We developed a tool, AmpliconArchitect (AA), which can robustly reconstruct the fine structure of focally amplified regions using whole genome sequencing. AA-reconstructed amplicons in pan-cancer data and in virus-driven cervical cancer samples revealed many novel insights about focal amplifications. Specifically, the findings lend support to extrachromosomally mediated mechanisms for copy number expansion, and oncoviral pathogenesis.

bioinformatics↗