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Biomedical subjects

Youngmin Han

Publications and source records attributed to Youngmin Han.

2 recordsLinked to original sources

Complete genomes from a xenic Dolichospermum flosaquae FBCC-A233 culture reveal genome-inferred metabolic asymmetry with associated bacteria.

Cyanobacteria form phycosphere communities with associated bacteria, but genome-resolved resources are needed to formulate testable hypotheses about their metabolic interactions. Here, we reconstructed three complete circular genomes from a unialgal xenic culture, including Dolichospermum flosaquae FBCC-A233 and two associated alphaproteobacterial genomes assigned to Sphingorhabdus sp. and Brevundimonas sp. Genome-wide read mapping and genome-quality assessment supported the three recovered genomes as high-quality circular reconstructions. Comparative genome analysis placed the cyanobacterial genome within the Dolichospermum flosaquae species cluster under the GTDB framework, while the associated bacterial genomes represented Sphingorhabdus sp. and a putative undescribed Brevundimonas species-level lineage. Genome architecture analysis indicated reduced genome size and gene content in Brevundimonas relative to genus-level references although additional metrics did not support a strong conclusion of classical genome streamlining. Selected KEGG module and KO-level reconstructions indicated genome-inferred metabolic asymmetries across the consortium. FBCC-A233 encoded photosynthesis- and nitrogen-related modules and a BioU-mediated de novo biotin biosynthesis route, whereas the associated bacteria lacked complete de novo biotin biosynthesis but retained biotin-dependent carboxylase genes. FBCC-A233 also encoded extensive anaerobic corrinoid biosynthesis potential; however, canonical DMB-containing cobalamin completion, cobamide identity, and complete transporter systems were not resolved. Together, these complete genomes provide a genome-resolved resource for investigating genome-inferred metabolic differentiation and ecological interactions in cyanobacteria-associated bacterial consortia.IMPORTANCEPhycosphere interactions between cyanobacteria and associated bacteria can shape aquatic microbial communities, but many proposed interactions remain difficult to evaluate without genome-resolved resources. This study provides three complete circular genomes from a unialgal xenic Dolichospermum flosaquae culture, capturing the cyanobacterium and two co-maintained bacterial associates. Our analysis identifies genome-inferred metabolic asymmetries, particularly in biotin- and cobamide-related pathways. D. flosaquae FBCC-A233 encoded candidate de novo biotin and corrinoid biosynthesis capacity, whereas the associated bacteria lacked complete de novo pathways but retained cofactor-dependent enzymes. These findings nominate cofactor-related dependencies as experimentally testable hypotheses while emphasizing unresolved uptake, export, cobamide identity, and growth-dependence mechanisms. The complete genomes and KO-level reconstructions generated here provide a resource for future studies of cyanobacteria-associated consortia.

Genome, Bacterial

Development of a Fit-For-Purpose Multi-Marker Panel for Early Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) suffers from a lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for the discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating the analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, the throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from the early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In the discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including a short gradient (<10&#xa0;min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

Humans