Biology subjects

Khare, H.

Publications and source records attributed to Khare, H..

3 recordsLinked to original sources

bioRxiv2023

CellWalker: A user-friendly and modular computational pipeline for morphological analysis of microscopy images

The implementation of computational tools for analysis of microscopy images has been one of the most important technological innovations in biology, providing researchers unmatched capabilities to comprehend cell shape and connectivity. Most available tools frequently focus either on segmentation or morphological analysis, thus not providing an inclusive pipeline. We introduce CellWalker, a computational pipeline that streamlines and connects the segmentation step with the morphological analysis in a modular manner. This python-based pipeline starts with visible-source IPython notebooks for segmentation of 2D/3D microscopy images using deep learning and visualization of the segmented images. The next module of CellWalker runs inside Blender, an open-source computer graphics software. This addon provides several morphometric analysis tools that can be used to calculate distances, volume, surface areas and to determine cross-sectional properties. It also includes tools to build skeletons, calculate distributions of sub-cellular organelles. Overall, CellWalker provides practical tools for segmentation and morphological analysis of microscopy images in the form of an open-source and modular pipeline which allows a complete access to fine-tuning of algorithms through visible source code while still retaining a result-oriented interface. Contactharshkhare@gmail.com, chiara.zurzolo@pasteur.fr Availability and implementationCellWalker source code is available on GitHub (https://github.com/utraf-pasteur-institute/CellWalker-notebooks and https://github.com/utraf-pasteur-institute/CellWalker-blender) under a GPL-3 license.

bioinformatics↗

bioRxiv2022

3D reconstruction of the cerebellar germinal layer reveals intercytoplasmic connections between developing granule cells

SummaryThe difficulty of retrieving high-resolution, in vivo evidence of the proliferative- and migratory processes occurring in neural germinal zones has limited our understanding of neurodevelopmental mechanisms. Here, we employed a connectomic approach using a high-resolution, serial-sectioning scanning electron microscopy volume to investigate the laminar cytoarchitecture of the transient external granular layer (EGL) of the developing cerebellum, where granule cells coordinate a series of mitotic and migratory events. By integrating image segmentation, 3D reconstruction, and deep learning approaches, we discovered and characterized anatomically complex intercellular connections bridging pairs of cerebellar granule cells throughout the EGL. Connected cells were either mitotic, migratory, or transitioning between these two cell stages, displaying a chronological continuum of proliferative and migratory events never previously observed in vivo at this resolution. This unprecedented ultra-structural characterization poses intriguing hypotheses about intercellular connectivity between developing progenitors, and its possible role in the development of the central nervous system (CNS).

neuroscience↗

bioRxiv2019

A short commentary on indents and edges of β-sheets

{beta}-sheets in proteins are formed by extended polypeptide chains, called {beta}-strands. While there is a general consensus on two types of {beta}-strands, viz. edge strands (or edges) and inner strands (or central strands), the possibility of distinguishing between different regions of inner strands remains less explored. In this paper, we address the portions of inner strands of {beta}-sheets that stick out on either or both sides. We call these portions the indent strands or indents because they give the typical indented appearance to {beta}-sheets. Similar to the edge strands, the indent strands also have {beta}-bridge partner residues on one side while the other side is still open for backbone hydrogen bonds. Despite this similarity, the indent strands differ from the edge strands in terms of various properties such as {beta}-bulges and amino acid composition due to their localization within {beta}-sheets and therefore within folded proteins to certain extent. The localization of indents and edges within folded proteins seems to govern the strategies deployed to deter unhindered {beta}-sheet propagation through {beta}-strand stacking interactions. Our findings suggest that, edges and indents differ in their strategies to avoid further {beta}-strand stacking. Short length itself is a good strategy to avoid stacking and a majority of indents are two residue or shorter in length. Edge strands on the other hand are overall longer. While long edges are known to use various negative design strategies like {beta}-bulges, prolines, strategically placed charges, inward-pointing charged side chains and loop coverage to avoid further {beta}-strand stacking, long indents seem to favor mechanisms such as enrichment in flexible residues with high solvation potential and depletion in hydrophobic residues in response to their less solvent exposed nature. Such subtle differences between indents and edges could be leveraged for designing novel {beta}-sheet architectures.

bioinformatics↗