Biology subjects

Chen, W. J.

Publications and source records attributed to Chen, W. J..

5 recordsLinked to original sources

bioRxiv2026

scFAIR Consortium: a decentralized hub for single-cell RNA-Seq data standardization and unification

The rapid accumulation of single-cell RNA-Seq (scRNA-seq) data across multiple repositories presents major challenges for data accessibility, integration, and reproducibility. While primary repositories provide raw data, they rarely include structured cell-type annotations or descriptions of analytical workflows, limiting the ability to reuse and integrate datasets in a FAIR (Findable, Accessible, Interoperable, Reusable) manner. Here we present scFAIR, a consortium of single-cell data resources that has developed a unified metadata schema and common curation framework to improve the FAIRness of scRNA-seq data. Building on and extending the CZ CELLxGENE Discover metadata schema, the scFAIR consortium has been instrumental in driving key schema improvements, including the expansion of supported organisms, richer biological context, and structured reporting of computational workflows. To provide unified access to decentralized datasets, the consortium developed the sc-fair.org portal, which currently aggregates 2,346 datasets across partner resources through ontology-aware semantic search. We demonstrate the practical value of FAIR-compliant datasets through a cross-species validation between human and mouse Allen Brain Atlases, showing that standardized ontology annotations enable reliable annotation transfer across species, with 90% of neuronal clusters receiving an exact or equivalent label. Together, the scFAIR schema, validator, and portal constitute a community-driven framework that advances single-cell data standardization and lays the foundation for reproducible, large-scale integration of single-cell datasets.

bioinformatics↗

bioRxiv2023

Single-molecule acceptor rise time (smART) FRET for nanoscale distance sensitivity

The structure, dynamics, and binding of individual biomolecules have been extensively investigated using single-molecule Forster resonance energy transfer (smFRET) as a spectroscopic ruler. The FRET efficiency between a fluorophore pair is used to measure distances in the several nanometer range. Existing approaches to detect closer distances come at the expense of sensitivity to longer distances. Here, we introduce single-molecule acceptor rise-time (smART) FRET that spans closer and longer distances. The acceptor rise time encodes the FRET rate, which scales polynomially with distance and thus has a steep dependence that expands the working range by 50%. High precision and accuracy is achieved through the spectroscopic separation between the rise time and the photophysical fluctuations that obfuscate other FRET readouts. Using the nanoscale sensitivity, we resolved the architectures of DNA bound to the single-stranded binding protein from E. coli, demonstrating the ability of smART FRET to elucidate the complex behaviors of biomolecules.

biophysics↗

bioRxiv2020

Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations

Genes enriched for rare disruptive coding variants in schizophrenia overlap those in which disruptive mutations are associated with neurodevelopmental disorders (NDDs), particularly autism spectrum disorders and intellectual disability. However, it is unclear whether this implicates the same specific variants, or even variants with the same functional effects on shared risk genes. Here, we show that de novo mutations in schizophrenia are generally of the same functional category as those that confer risk for NDDs, and that the specific de novo mutations in NDDs are enriched in schizophrenia. These findings indicate that, in part, NDDs and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology. We also observe pleiotropic effects for variants known to be pathogenic for several syndromic developmental disorders, suggesting that schizophrenia should be included among the phenotypes associated with these mutations. Collectively, our findings support the hypothesis that at least some forms of schizophrenia lie within a continuum of neurodevelopmental disorders.

genetics↗

bioRxiv2019

Thrombospondin-1 Promotes Circuit-Specific Synapse Formation via β1-Integrin

Glial cells regulate synaptic connectivity during development, but whether they selectively instruct the formation of specific synaptic circuits is not known. Here we show that the major perisynaptic glia of the retina, the Muller glia (MG), control the proper establishment of the direction-selective (DS) circuit by a synaptogenic protein, Thrombospondin 1 (TSP1). We found that TSP1 promotes excitatory synapse formation specifically in on-off Direction-Selective retinal Ganglion Cells (ooDSGCs). Lack of TSP1 leads to reduced synapse formation within the inner plexiform sublayers containing DS-circuit, resulting in deficits of ooDSGC function. Even though pan-TSP receptor, 2{delta}-1, interaction is required for TSP1-induced synapse formation, the ooDSGC-subtype specificity of TSP1 is conferred by a second neuronal TSP1 receptor, {beta}1-Integrin. Furthermore, conditional deletion of {beta}1-Integrin in ooDSGCs results in diminished excitatory synapse formation without disturbing laminar organization showing that MG-secreted TSP1 controls circuit-specific synapse formation via {beta}1-Integrin.

neuroscience↗

bioRxiv2018

Schizophrenia risk conferred by protein-coding de novo mutations

Protein-coding de novo mutations (DNMs) in the form of single nucleotide changes and short insertions/deletions are significant genetic risk factors for autism, intellectual disability, developmental delay, and epileptic encephalopathy. In contrast, the burden of DNMs has thus far only had a modest documented impact on schizophrenia (SCZ) risk. Here, we analyze whole-exome sequence from 1,695 SCZ affected parent-offspring trios from Taiwan along with DNMs from 1,077 published SCZ trios to better understand the contribution of coding DNMs to SCZ risk. Among 2,772 SCZ affected probands, the increased burden of DNMs is modest. Gene set analyses show that the modest increase in risk from DNMs in SCZ probands is concentrated in genes that are either highly brain expressed, under strong evolutionary constraint, and/or overlap with genes identified as DNM risk factors in other neurodevelopmental disorders. No single gene meets the criteria for genome-wide significance, but we identify 16 genes that are recurrently hit by a protein-truncating DNM, which is a 3.15-fold higher rate than mutation model expectation of 5.1 genes (permuted 95% CI=1-10 genes, permuted p=3e-5). Overall, DNMs explain only a small fraction of SCZ risk, and this risk is polygenic in nature suggesting that coding variation across many different genes will be a risk factor for SCZ in the population.

genetics↗