Single-cell network biology enabling cell-type-resolved disease genetics DOI Creative Commons
Junha Cha, Insuk Lee

Genomics & Informatics, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 27, 2025

Abstract Gene network models provide a foundation for graph theory approaches, aiding in the novel discovery of drug targets, disease genes, and genetic mechanisms various biological functions. Disease genetics must be interpreted within cellular context disease-associated cell types, which cannot achieved with datasets consisting solely organism-level samples. Single-cell RNA sequencing (scRNA-seq) technology allows computational distinction states provides unique opportunity to understand biology that drives processes. Importantly, abundance samples their transcriptome-wide profile modeling systemic cell-type-specific gene networks (CGNs), offering insights into gene-cell-disease relationships. In this review, we present reference-based de novo inference functional interaction have recently developed using scRNA-seq datasets. We also introduce compendium CGNs as useful resource cell-type-resolved genetics. By leveraging these advances, envision single-cell key approach mapping axis.

Language: Английский

Comparative Analysis of Commercial Single-Cell RNA Sequencing Technologies DOI Creative Commons
Marco De Simone,

Jonathan Hoover,

J. Lau

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 18, 2024

Abstract This study evaluates ten commercially available single-cell RNA sequencing (scRNA-seq) approaches across four technology groups: Emulsion-based kits from 10x Genomics and Fluent Biosciences; Microwell-based Becton Dickinson, Honeycomb Technologies Singerlon Technologies; Combinatorial-indexing Parse Biosciences Scale a Matrigel-based kit Scipio Biosciences. Peripheral blood mononuclear cells (PBMCs) single donor were used to assess analytical performance. Key features such as sample compatibility, cost, experimental duration also compared. Notably, superior performance was demonstrated by the Chromium Fixed Profiling Genomics, which uniquely probe hybridization for transcript detection. Additionally, Rhapsody WTA Dickinson provided cost-effective balance of expense per cell. With rich dataset 218,154 cells, this work provides basis differentiating commercial scRNA-seq technologies, is intended facilitate effective application further methodological development cell transcriptomics.

Language: Английский

Citations

9
Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis DOI
Joona Sarkkinen, Dawit Yohannes,

Nea Kreivi

et al.

Science Immunology, Journal Year: 2025, Volume and Issue: 10(104)

Published: Feb. 21, 2025

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, and Epstein-Barr virus (EBV) infection a prerequisite for developing disease. However, pathogenic mechanisms that lead to MS remain be determined. Here, we characterized immune landscape deep cervical lymph nodes (dcLNs) in newly diagnosed untreated patients with (pwMS) using fine-needle aspirations. By combining single-cell RNA sequencing cellular indexing transcriptomes epitopes by sequencing, observed increased memory B cells reduced germinal center decreased clonality pwMS. Double-negative were pwMS transcriptionally resembled lytic EBV infection. Moreover, EBV-targeting CD8 T detected subset We also DNA dcLNs elevated viral loads patient saliva. These findings suggest EBV-driven cell dysregulation critical mechanism pathogenesis.

Language: Английский

Citations

1
Improved T cell receptor antigen pairing through data-driven filtering of sequencing information from single cells DOI Creative Commons
Helle Rus Povlsen, Amalie Kai Bentzen, Mohammad Kadivar

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 3, 2023

Novel single-cell-based technologies hold the promise of matching T cell receptor (TCR) sequences with their cognate peptide-MHC recognition motif in a high-throughput manner. Parallel capture TCR transcripts and is enabled through use reagents labeled DNA barcodes. However, analysis annotation such single-cell sequencing (SCseq) data are challenged by dropout, random noise, other technical artifacts that must be carefully handled downstream processing steps. We here propose rational, data-driven method termed ITRAP (improved Receptor Antigen Paring) to deal these challenges, filtering away likely artifacts, enable generation large sets TCR-pMHC sequence high degree specificity sensitivity, thus outputting most pMHC target per cell. have validated this approach across 10 different virus-specific responses 16 healthy donors. Across samples, we identified up 1494 high-confident pairs derived from 4135 single cells.

Language: Английский

Citations

17
Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas DOI Creative Commons
Wei E. Gordon, Seungbyn Baek, Hai P. Nguyen

et al.

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

Published: Jan. 9, 2024

Abstract Frugivory evolved multiple times in mammals, including bats. However, the cellular and molecular components driving it remain largely unknown. Here, we use integrative single-cell sequencing (scRNA-seq scATAC-seq) on insectivorous ( Eptesicus fuscus ; big brown bat) frugivorous Artibeus jamaicensis Jamaican fruit bat kidneys pancreases identify key cell population, gene expression regulatory differences associated with that also relate to human disease, particularly diabetes. We find a decrease loop of Henle an increase collecting duct cells, differentially active genes elements involved fluid electrolyte balance kidney. The pancreas shows endocrine exocrine insulin regulation. these bats share several characteristics Combined, our work provides insights from mammal could be leveraged for therapeutic purposes.

Language: Английский

Citations

7
High-Throughput Functional Screening of Antigen-Specific T Cells Based on Droplet Microfluidics at a Single-Cell Level DOI
Shiyu Wang, Yang Liu, Yijian Li

et al.

Analytical Chemistry, Journal Year: 2021, Volume and Issue: 94(2), P. 918 - 926

Published: Dec. 1, 2021

The lack of an efficient method for the identification tumor antigen-specific T cell receptors (TCRs) impedes development cell-based cancer immunotherapies. Here, we introduce a droplet-based microfluidic platform function-based screening and sorting cells with high throughput. We built reporter line by co-transducing TCR library genes at downstream signaling, fluoresced upon functionally binding antigens. co-encapsulated antigen-presenting in droplets to allow stimulation on single-cell level. Functioning specific against antigen were identified channel based fluorescent signals droplets, which immediately sorted out using dielectrophoresis. validated system results flow cytometry. then performed RNA sequencing further validate this demonstrate compatibility genetic characterizations. Our provides means precise immunotherapy, high-throughput could potentially facilitate immunotherapeutic promote anti-tumor therapies.

Language: Английский

Citations

33
Microfluidic techniques for isolation, formation, and characterization of circulating tumor cells and clusters DOI Creative Commons

Celine Macaraniag,

Qiyue Luan, Jian Zhou

et al.

APL Bioengineering, Journal Year: 2022, Volume and Issue: 6(3)

Published: July 15, 2022

Circulating tumor cell (CTC) clusters that are shed from the primary into bloodstream associated with a poor prognosis, elevated metastatic potential, higher proliferation rate, and distinct molecular features compared to single CTCs. Studying CTC may give us information on differences in genetic profiles, somatic mutations, epigenetic changes circulating cells sites. Microfluidic systems offer means of studying through ability efficiently isolate these rare whole blood patients liquid biopsy. Microfluidics can also be used develop

Language: Английский

Citations

28
Deciphering the Biology of Circulating Tumor Cells through Single-Cell RNA Sequencing: Implications for Precision Medicine in Cancer DOI Open Access
Santhasiri Orrapin, Patcharawadee Thongkumkoon, Sasimol Udomruk

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12337 - 12337

Published: Aug. 2, 2023

Circulating tumor cells (CTCs) hold unique biological characteristics that directly involve them in hematogenous dissemination. Studying CTCs systematically is technically challenging due to their extreme rarity and heterogeneity the lack of specific markers specify metastasis-initiating CTCs. With cutting-edge technology, single-cell RNA sequencing (scRNA-seq) provides insights into biology metastatic processes driven by Transcriptomics analysis single can decipher phenotypic plasticity for exploring promising novel therapeutic targets. The integrated approach a perspective on mechanisms underlying development interrogates interactions with other blood cell types, particularly those immune system. This review aims comprehensively describe current study CTC transcriptomic through scRNA-seq technology. We emphasize workflow CTCs, including enrichment, isolation, bioinformatic tools applied this purpose. Furthermore, we elucidated translational knowledge from profile individual cancer metastasis developing effective therapeutics targeting key pathways

Language: Английский

Citations

16
Influenza virus transcription and progeny production are poorly correlated in single cells DOI Creative Commons
David J. Bacsik, Bernadeta Dadonaite, Andrew Butler

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 12, 2023

The ultimate success of a viral infection at the cellular level is determined by number progeny virions produced. However, most single-cell studies quantify expression transcripts and proteins, rather than amount released from infected cells. Here, we overcome this limitation simultaneously measuring transcription production single influenza virus-infected cells embedding nucleotide barcodes in genome. We find that are poorly correlated transcribe mRNA do not produce often represent aberrant infections fail to express NS gene. only some discrepancy between can be explained gene absence or mutations: there also wide range among complete unmutated virions. Overall, our results show relatively poor predictor an cell's contribution population.

Language: Английский

Citations

15
Single-cell and spatial transcriptomics: Bridging current technologies with long-read sequencing DOI
Chengwei Ulrika Yuan, Fu Xiang Quah, Martin Hemberg

et al.

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 96, P. 101255 - 101255

Published: Feb. 17, 2024

Language: Английский

Citations

6
The genome and preliminary single-nuclei transcriptome ofLemna minutareveals mechanisms of invasiveness DOI Creative Commons
Bradley W. Abramson, Mark Novotny, Nolan Hartwick

et al.

PLANT PHYSIOLOGY, Journal Year: 2021, Volume and Issue: 188(2), P. 879 - 897

Published: Dec. 2, 2021

The ability to trace every cell in some model organisms has led the fundamental understanding of development and cellular function. However, plants complexity number, organ size, developmental time makes this a challenge even diminutive plant Arabidopsis (Arabidopsis thaliana). Duckweed, basal nongrass aquatic monocots, provide an opportunity follow entire due their small reduced body plan, fast clonal growth habit. Here we present chromosome-resolved genome for highly invasive Lesser Duckweed (Lemna minuta) generate preliminary atlas leveraging low coverage single-nuclei sequencing. We resolved 360 megabase into 21 chromosomes, revealing core nonredundant gene set with only ancient tau whole-genome duplication shared all paralog expansion as result tandem duplications related phytoremediation. Leveraging SMARTseq2 sequencing, which provided higher yet lower count, profiled 269 nuclei covering 36.9% (8,457) L. minuta transcriptome. Since molecular validation was not possible nonmodel plant, leveraged orthology organism single-cell expression datasets, ontology, trajectory analysis define putative types. found that tissue computationally defined mesophyll expressed high levels elemental transport genes consistent playing role wastewater detoxification. map paradigm decipher pathways plant.

Language: Английский

Citations

24