Understanding isoform expression by pairing long-read sequencing with single-cell and spatial transcriptomics DOI
Natan Belchikov, Justine Hsu, X. Li

et al.

Genome Research, Journal Year: 2024, Volume and Issue: 34(11), P. 1735 - 1746

Published: Nov. 1, 2024

RNA isoform diversity, produced via alternative splicing, and usage of transcription start poly(A) sites, results in varied transcripts being derived from the same gene. Distinct isoforms can play important biological roles, including by changing sequences or expression levels protein products. The first single-cell approaches to sequencing—and later, spatial approaches—which are now widely used for identification differentially expressed genes, rely on short reads offer ability transcriptomically compare different cell types but limited their measure differential expression. More recently, long-read sequencing methods have been combined with technologies order characterize In this review, we provide an overview emergence discuss challenges associated implementation these interpretation data. We opportunities they understanding relationships between distinct variable elements transcript molecules highlight some ways which isoforms’ roles development pathology. Single-nucleus sequencing, a special case approach, is also discussed. attempt cover both limitations significant potential expanding our still-limited isoforms.

Language: Английский

Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population DOI Creative Commons
William Wang, Nora D. Volkow, Nathan A. Berger

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 28, 2024

Abstract Alcohol use disorders are among the top causes of global burden disease, yet therapeutic interventions limited. Reduced desire to drink in patients treated with semaglutide has raised interest regarding its potential benefits for alcohol disorders. In this retrospective cohort study electronic health records 83,825 obesity, we show that compared other anti-obesity medications is associated a 50%-56% lower risk both incidence and recurrence disorder 12-month follow-up period. Consistent reductions were seen stratified by gender, age group, race without type 2 diabetes. Similar findings replicated population 598,803 These provide evidence benefit AUD real-world populations call further randomized clinical trials.

Language: Английский

Citations

29
Multi-omic Characterization of HIV Effects at Single Cell Level across Human Brain Regions DOI Creative Commons
Junchen Yang, Kriti Agrawal, Jay S. Stanley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Abstract HIV infection exerts profound and long-lasting neurodegenerative effects on the central nervous system (CNS) that can persist despite antiretroviral therapy (ART). Here, we used single-nucleus multiome sequencing to map transcriptomic epigenetic landscapes of postmortem human brains from 13 healthy individuals 20 with who have a history treatment ART. Our study spanned three distinct regions—the prefrontal cortex, insular ventral striatum—enabling comprehensive exploration region-specific cross-regional perturbations. We found widespread persistent HIV-associated transcriptional alterations across multiple cell types. Detailed analyses microglia revealed state changes marked by immune activation metabolic dysregulation, while integrative multiomic profiling astrocytes identified subpopulations, including reactive subpopulation unique HIV-infected brains. These findings suggest cells people exhibit molecular shifts may underlie ongoing neuroinflammation CNS dysfunction. Furthermore, cell–cell communication uncovered dysregulated pro-inflammatory interactions among glial populations, underscoring multifaceted enduring impact brain milieu. Collectively, our atlas reveals states signatures signaling providing framework for developing targeted therapies neurological

Language: Английский

Citations

0
Principled PCA separates signal from noise in omics count data DOI Creative Commons
Jay S. Stanley, Junchen Yang, Ruiqi Li

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Abstract Principal component analysis (PCA) is indispensable for processing high-throughput omics datasets, as it can extract meaningful biological variability while minimizing the influence of noise. However, suitability PCA contingent on appropriate normalization and transformation count data, accurate selection number principal components; improper choices result in loss information or corruption signal due to excessive Typical approaches these challenges rely heuristics that lack theoretical foundations. In this work, we present Biwhitened (BiPCA), a theoretically grounded framework rank estimation data denoising across wide range modalities. BiPCA overcomes fundamental difficulty with handling noise by adaptively rescaling rows columns – rigorous procedure standardizes variances both dimensions. Through simulations over 100 datasets spanning seven modalities, demonstrate reliably recovers enhances interpretability data. particular, marker gene expression, preserves cell neighborhoods, mitigates batch effects. Our results establish robust versatile analysis.

Language: Английский

Citations

0
Transcriptomic Alterations Induced by Tetrahydrocannabinol in SIV/HIV Infection: A Systematic Review DOI Open Access
Amir Valizadeh, Rebecca T. Veenhuis,

Brooklyn Bradley

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2598 - 2598

Published: March 13, 2025

Given the high prevalence of cannabis use among people with HIV (PWH) and its potential to modulate immune responses reduce inflammation, this systematic review examines preclinical evidence on how tetrahydrocannabinol (THC), a key compound in cannabis, affects gene micro-RNA expression simian immunodeficiency virus (SIV)-infected macaques HIV-infected human cells. Through comprehensive search, 19 studies were identified, primarily involving SIV-infected macaques, pooled sample size 176, though methodological quality varied across studies. Pathway analysis differentially expressed genes (DEGs) miRNAs associated THC revealed enrichment pathways related epithelial cell proliferation, adhesion. Notably, some DEGs targets miRNAs, suggesting that epigenetic regulation may contribute THC’s effects function. These findings indicate help mitigate chronic activation infection by altering miRNA expression, immunomodulatory role. However, is constrained small sizes inconsistencies Further research employing advanced methodologies larger cohorts essential confirm as complementary therapy for PWH fully elucidate underlying mechanisms, which could inform targeted interventions harness effects.

Language: Английский

Citations

0
Management of pain and other palliative needs in older people with HIV DOI

Niyati Neupane,

Mitali Mehta,

Jessica Robinson‐Papp

et al.

Current Opinion in HIV and AIDS, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Purpose of review Human immunodeficiency virus (HIV) was historically considered a terminal illness. However, medical advancements, including antiretroviral therapy (ART), have extended the lifespan people with HIV (PWH), emphasizing importance maximizing quality life (QoL) in this aging population. These populations face unique health challenges due to various structural and environmental barriers, comorbidities. This aims consolidate recent data on pain management other palliative needs older (OPWH ). Recent findings research developments focus providing relief by incorporation geriatric care (PC) principles, use long-acting injectable-antiretroviral therapies (LAI-ARTs), cannabinoids, exercise self-management interventions, tailored cognitive-behavioral (CBT) for (OPWH; ≥50 years). The potential these novel interventions can fulfil underserved demographic suffering from niche subset physical psychosocial issues. Yet, there remains variability access services, disparities often linked healthcare infrastructure socioeconomic factors. Summary Interventions an population PWH should take person-centered approach, balancing different priorities exploring multiple avenues symptom relief.

Language: Английский

Citations

0
Understanding isoform expression by pairing long-read sequencing with single-cell and spatial transcriptomics DOI
Natan Belchikov, Justine Hsu, X. Li

et al.

Genome Research, Journal Year: 2024, Volume and Issue: 34(11), P. 1735 - 1746

Published: Nov. 1, 2024

RNA isoform diversity, produced via alternative splicing, and usage of transcription start poly(A) sites, results in varied transcripts being derived from the same gene. Distinct isoforms can play important biological roles, including by changing sequences or expression levels protein products. The first single-cell approaches to sequencing—and later, spatial approaches—which are now widely used for identification differentially expressed genes, rely on short reads offer ability transcriptomically compare different cell types but limited their measure differential expression. More recently, long-read sequencing methods have been combined with technologies order characterize In this review, we provide an overview emergence discuss challenges associated implementation these interpretation data. We opportunities they understanding relationships between distinct variable elements transcript molecules highlight some ways which isoforms’ roles development pathology. Single-nucleus sequencing, a special case approach, is also discussed. attempt cover both limitations significant potential expanding our still-limited isoforms.

Language: Английский

Citations

3