Biomedical discovery through the integrative biomedical knowledge hub (iBKH)

iScience, Journal Year: 2023, Volume and Issue: 26(4), P. 106460 - 106460

Published: March 21, 2023

The abundance of biomedical knowledge gained from biological experiments and clinical practices is an invaluable resource for biomedicine. emerging graphs (BKGs) provide efficient effective way to manage the abundant in life science. In this study, we created a comprehensive BKG called integrative Biomedical Knowledge Hub (iBKH) by harmonizing integrating information diverse resources. To make iBKH easily accessible research, developed web-based, user-friendly graphical portal that allows fast interactive retrieval. Additionally, also implemented scalable graph learning pipeline discovering novel iBKH. As proof concept, performed our iBKH-based method computational in-silico drug repurposing Alzheimer's disease. publicly available.

Language: Английский

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Genomic signatures of adaptation in native lizards exposed to human-introduced fire ants

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Understanding the process of genetic adaptation in response to human-mediated ecological change will help elucidate eco-evolutionary impacts human activity. In 1930s red imported fire ants (Solenopsis invicta) were accidently introduced Southeastern USA, where today they are both venomous predators and toxic prey native eastern fence lizards (Sceloporus undulatus). Here, we investigate potential lizard invasive by generating whole-genome sequences from 420 across three populations: one with long exposure ants, two unexposed populations. Signatures positive selection exclusive exposed population overlap immune system, growth factor pathway, morphological development genes. Among invaded lizards, longer limbs (used remove stinging ants) associated increased survival. We identify alleles that highly differentiated populations, a pattern counter pre-invasion latitudinal cline for limb lengths based on museum specimens. While cannot rule out other environmental differences between populations driving these patterns, results do constitute plausible adaptations ants. Red North America 1930s, since then imposing novel selective pressures ecosystems. This study identifies genomic signatures recent potentially linked

Language: Английский

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Marfan syndrome variation of the POGLUT2 and POGLUT3 consensus sequence can produce aberrant fibrillin-1 O-glucosylation

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108411 - 108411

Published: March 1, 2025

Fibrillin-1 (FBN1) is an essential component of the extracellular matrix, forming microfibril bundles that are important for proper development elastic tissues found in aorta and lung, as well non-elastic tissue eyes skeleton. Many missense mutations FBN1 gene associated with Marfan syndrome (MFS), a common developmental disorder. contains 47 Epidermal Growth Factor-Like (EGF) repeats, which protein domains characterized by six cysteines (C) three disulfide bonds. Over half these EGF repeats modified O-glucose monosaccharide added Protein O-glucosyltransferase 2 and/or 3 (POGLUT2/3). Previous studies showed modifies serine within putative consensus sequence between C four: C3-x-N-T-x-G-S-F/Y-x-C4. These residues among EGFs, but it unknown if they required O-glucosylation. To address this, we used glycoproteomic approach analyzing O-glucosylation levels individual from overexpressed N-terminal variants HEK293T cells. Surprisingly, only (S) was O-glucosylation, leading to revised sequence, C3-x-x-x-x-x-S-x-x-C4. Using this open database searches, possible number POGLUT2/3 substrates humans has doubled. While some displayed reduced modification, other variants, including MFS elongation additional glycosyltransferases. reduction or warrants further investigation on their influence function, could play role molecular mechanism disease.

Language: Английский

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RBPMS2 Is a Myocardial-Enriched Splicing Regulator Required for Cardiac Function

Circulation Research, Journal Year: 2022, Volume and Issue: 131(12), P. 980 - 1000

Published: Nov. 11, 2022

RBPs (RNA-binding proteins) perform indispensable functions in the post-transcriptional regulation of gene expression. Numerous have been implicated cardiac development or physiology based on knockout studies and identification pathogenic RBP mutations monogenic heart disorders. The discovery characterization additional performing will advance basic translational cardiovascular research.

Language: Английский

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In vivo CRISPR screening directly targeting testicular cells

Cell Genomics, Journal Year: 2024, Volume and Issue: 4(3), P. 100510 - 100510

Published: March 1, 2024

CRISPR-Cas9 short guide RNA (sgRNA) library screening is a powerful approach to understand the molecular mechanisms of biological phenomena. However, its in vivo application currently limited. Here, we developed our previously established vitro revival method into an one identify factors involved spermatogenesis integrity by utilizing sperm capacitation as indicator. By introducing sgRNA testicular cells, successfully pinpointed retinal degeneration 3 (Rd3) gene significant factor spermatogenesis. Single-cell sequencing (scRNA-seq) analysis highlighted high expression Rd3 round spermatids, and proteomics indicated that interacts with mitochondria. To search for cell-type-specific signaling pathways based on scRNA-seq analyses, computational tool, Hub-Explorer. Through this, discovered modulates oxidative stress regulating mitochondrial distribution upon ciliogenesis induction. Collectively, system provides valuable decipher processes.

Language: Английский

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