Biology subjects

Lin, C.-F.

Publications and source records attributed to Lin, C.-F..

4 recordsLinked to original sources

bioRxiv2025

Tissue-guided multi-omics profiling identifies extracellular vesicle biomarkers indicative of lung pathology in acute respiratory distress syndrome

BackgroundAcute respiratory distress syndrome (ARDS) remains a lethal inflammatory lung condition lacking reliable biomarkers that reflect lung-specific pathology. Extracellular vesicles (EVs) circulate systemically and may carry molecular signals from injured organs, but the correspondence between EV cargo and lung tissue alterations remains unclear. MethodsWe established aspiration-, lipopolysaccharide (LPS)-, and COVID-19-induced murine ARDS models and applied a tissue-guided multiomics framework integrating proteomic and metabolomic analyses of lung tissue and plasma-derived EVs to identify lung-originating circulating biomarkers. ResultsFour proteins--haptoglobin (HP), inter-alpha-trypsin inhibitor heavy chains 3 and 4 (ITIH3, ITIH4), and clusterin (CLU)--were consistently upregulated in both lung tissue and plasma EVs across all ARDS etiologies. Metabolomic integration revealed dysregulation of arachidonic acid metabolism as a unifying inflammatory axis. Multiomics network analysis further distinguished etiology-specific molecular programs, including glycolytic activation in aspiration-induced, platelet aggregation in LPS-induced, and vascular smooth muscle dysregulation in COVID-19-induced ARDS. ConclusionsThis study establishes a tissue-informed EV profiling framework that links local lung pathology to systemic molecular signatures, revealing HP, ITIH3, ITIH4, CLU, and arachidonic-acid-related metabolites as potential diagnostic markers for ARDS. These findings provide a foundation for developing clinically translatable, EV-based biomarker assays for early detection and molecular subtyping of lung injury.

biochemistry↗

bioRxiv2021

SARS-CoV-2-specific T cells in unexposed adults display broad trafficking potential and cross-react with commensal antigens

The baseline composition of T cells directly impacts later response to a pathogen, but the complexity of precursor states remains poorly defined. Here we examined the baseline state of SARS-CoV-2 specific T cells in unexposed individuals. SARS-CoV-2 specific CD4+ T cells were identified in pre-pandemic blood samples by class II peptide-MHC tetramer staining and enrichment. Our data revealed a substantial number of SARS-CoV-2 specific T cells that expressed memory phenotype markers, including memory cells with gut homing receptors. T cell clones generated from tetramer-labeled cells cross-reacted with bacterial peptides and responded to stool lysates in a MHC-dependent manner. Integrated phenotypic analyses revealed additional precursor diversity that included T cells with distinct polarized states and trafficking potential to other barrier tissues. Our findings illustrate a complex pre-existing memory pool poised for immunologic challenges and implicate non-infectious stimuli from commensal colonization as a factor that shapes pre-existing immunity. One Sentence SummaryPre-existing immunity to SARS-CoV-2 contains a complex pool of precursor lymphocytes that include differentiated cells with broad tissue tropism and the potential to cross-react with commensal antigens.

immunology↗

bioRxiv2018

A Rigorous Interlaboratory Examination of the Need to Confirm NGS-Detected Variants by an Orthogonal Method in Clinical Genetic Testing

Orthogonal confirmation of NGS-detected germline variants has been standard practice, although published studies have suggested that confirmation of the highest quality calls may not always be necessary. The key question is how laboratories can establish criteria that consistently identify those NGS calls that require confirmation. Most prior studies addressing this question have limitations: These studies are generally small, omit statistical justification, and explore limited aspects of the underlying data. The rigorous definition of criteria that separate high-accuracy NGS calls from those that may or may not be true remains a critical issue.\n\nWe analyzed five reference samples and over 80,000 patient specimens from two laboratories. We examined quality metrics for approximately 200,000 NGS calls with orthogonal data, including 1662 false positives. A classification algorithm used these data to identify a battery of criteria that flag 100% of false positives as requiring confirmation (CI lower bound: 98.5-99.8% depending on variant type) while minimizing the number of flagged true positives. These criteria identify false positives that the previously published criteria miss. Sampling analysis showed that smaller datasets resulted in less effective criteria.\n\nOur methodology for determining test and laboratory-specific criteria can be generalized into a practical approach that can be used by many laboratories to help reduce the cost and time burden of confirmation without impacting clinical accuracy.

genetics↗

bioRxiv2018

Development and worldwide use of a non-lethal and minimal population-level impact protocols for the isolation of chytrids from amphibians

Parasitic chytrid fungi have emerged as a significant threat to amphibian species worldwide, necessitating the development of techniques to isolate these pathogens into sterile culture for research purposes. However, early methods of isolating chytrids from their hosts relied on killing amphibians. We modified a pre-existing protocol for isolating chytrids from infected animals to use toe clips and biopsies from toe webbing rather than euthanizing hosts, and distributed the protocol to interested researchers worldwide as part of the BiodivERsA project RACE - here called the RML protocol. In tandem, we developed a lethal procedure for isolating chytrids from tadpole mouthparts. Reviewing a database of use a decade after their inception, we find that these methods have been widely applied across at least 5 continents, 23 countries and in 62 amphibian species, and have been successfully used to isolate chytrids in remote field locations. Isolation of chytrids by the non-lethal RML protocol occured in 18% of attempts with 207 fungal isolates and three species of chytrid being recovered. Isolation of chytrids from tadpoles occured in 43% of attempts with 334 fungal isolates of one species (Batrachochytrium dendrobatidis) being recovered. Together, these methods have resulted in a significant reduction and refinement of our use of threatened amphibian species and have improved our ability to work with this important group of emerging fungal pathogens.

ecology↗