Hidari, E. | Search bioRxiv

bioRxiv2025

WxS-QC - a quality control pipeline for human Whole-Genome and Whole Exome sequencing cohorts

MotivationWhole-exome (WES) and whole-genome (WGS) sequencing are rapidly becoming preferred methods for population-scale analysis of the human genetic landscape. However, there are currently no standardized quality control (QC) pipelines for human WES and WGS datasets. Moveover, there are no open datasets that can be used to test QC pipelines, because most projects (like 1000 genomes and gnomAD) publish only post-QC results. ResultsWe present WxS-QC, a powerful, scalable, and convenient pipeline for the QC of human WGS and WES cohorts, developed at the Wellcome Sanger Institute (WSI). Our pipeline is based on a deep refactoring of the gnomAD quality control pipeline code and is aligned with current best practices in WGS/WES cohort data QC. It offers a set of novel QC techniques, automatic export of resulting graphs and summary tables, excellent performance and scalability, and incorporates comprehensive documentation. To test our pipeline and similar solutions, we also assembled an open dataset with all required metadata. Availability and implementationThe pipeline code is written in Python using the Hail library and is freely available under the BSD-3 license here: https://github.com/wtsi-hgi/wxs-qc. It can run in any UNIX-like environment and has been able to efficiently process cohorts of up to 200,000 whole-exome samples with the potential to handle bigger datasets, depending on the available hardware. The detailed description of the pipeline, resources and test data is available in the pipeline documentation: https://github.com/wtsi-hgi/wxs-qc/blob/main/README.md The open test dataset is available to download from https://wxs-qc-data.cog.sanger.ac.uk/wxs-qc_public_dataset_v3.tar. An example of test dataset analysis is available in the supplementary materials.

bioinformatics↗

bioRxiv2020

CSPα reduces aggregates and rescues striatal dopamine release in αsynuclein transgenic mice

Synuclein aggregation at the synapse is an early event in Parkinsons disease and is associated with impaired striatal synaptic function and dopaminergic neuronal death. The cysteine string protein (CSP) and synuclein have partially overlapping roles in maintaining synaptic function and mutations in each cause neurodegenerative diseases. CSP is a member of the DNAJ/HSP40 family of co-chaperones and like synuclein, chaperones the SNARE complex assembly and neurotransmitter release. Synuclein can rescue neurodegeneration in CSPKO mice. However, whether synuclein aggregation alters CSP expression and function is unknown. Here we show that synuclein aggregation at the synapse induces a decrease in synaptic CSP and a reduction in the complexes that CSP forms with HSC70 and STGa. We further show that viral delivery of CSP rescues in vitro the impaired vesicle recycling in PC12 cells with synuclein aggregates and in vivo reduces synaptic synuclein aggregates restoring normal dopamine release in 1-120hsyn mice. These novel findings reveal a mechanism by which synuclein aggregation alters CSP at the synapse, and show that CSP rescues synuclein aggregation-related phenotype in 1-120hsyn mice similar to the effect of synuclein in CSPKO mice. These results implicate CSP as a potential therapeutic target for the treatment of early-stage PD.

neuroscience↗