FAVA: High-quality functional association networks inferred from scRNA-seq and proteomics data DOI Creative Commons
Mikaela Koutrouli, Pau Piera Líndez, Katerina Nastou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 7, 2022

Abstract Protein networks are commonly used for understanding how proteins interact. However, they typically biased by data availability, favoring well-studied with more interactions. To uncover functions of understudied proteins, we must use that not affected this literature bias, such as single-cell RNA-seq and proteomics. Due to sparseness redundancy, co-expression analysis becomes complex. address this, have developed FAVA (Functional Associations using Variational Autoencoders), which compresses high-dimensional into a low-dimensional space. infers from omics much higher accuracy than existing methods, across diverse collection real well simulated datasets. can process large datasets over 0.5 million conditions has predicted 4,210 interactions between 1,039 proteins. Our findings showcase FAVA’s capability offer novel perspectives on protein within the scverse ecosystem, employing AnnData its input source.

Language: Английский

Microglial expression of CD83 governs cellular activation and restrains neuroinflammation in experimental autoimmune encephalomyelitis DOI Creative Commons
Pia Sinner, Katrin Peckert-Maier, Hashem Mohammadian

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 1, 2023

Abstract Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue, and initial of microglia determines severity neuro-inflammatory diseases. The CD83 molecule has been recently shown to modulate status dendritic cells macrophages. Although expression associated with early in various disease settings, its functional relevance microglial biology elusive. Here, we describe a thorough assessment regulation show that murine not only cellular but also pro-resolving functions. Using single-cell RNA-sequencing, reveal conditional deletion results an over-activated state experimental autoimmune encephalomyelitis model. Subsequently, CD83-deficient recruit more pathogenic central nervous system, deteriorating resolving mechanisms exacerbating disease. Thus, orchestrates and, consequently, resolution neuroinflammation.

Language: Английский

Citations

29
Spatial Transcriptomics-correlated Electron Microscopy maps transcriptional and ultrastructural responses to brain injury DOI Creative Commons
Peter Androvic, Martina Schifferer,

Katrin Perez Anderson

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 11, 2023

Abstract Understanding the complexity of cellular function within a tissue necessitates combination multiple phenotypic readouts. Here, we developed method that links spatially-resolved gene expression single cells with their ultrastructural morphology by integrating multiplexed error-robust fluorescence in situ hybridization (MERFISH) and large area volume electron microscopy (EM) on adjacent sections. Using this method, characterized transcriptional responses glial infiltrating T-cells after demyelinating brain injury male mice. We identified population lipid-loaded “foamy” microglia located center remyelinating lesion, as well rare interferon-responsive microglia, oligodendrocytes, astrocytes co-localized T-cells. validated our findings using immunocytochemistry lipid staining-coupled single-cell RNA sequencing. Finally, these datasets, detected correlations between full-transcriptome features microglia. Our results offer an integrative view spatial, ultrastructural, reorganization injury.

Language: Английский

Citations

27
Spatially resolved transcriptomic analysis of the germinating barley grain DOI Creative Commons
Marta Peirats‐Llobet, Changyu Yi, Lim Chee Liew

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 51(15), P. 7798 - 7819

Published: June 23, 2023

Seeds are a vital source of calories for humans and unique stage in the life cycle flowering plants. During seed germination, embryo undergoes major developmental transitions to become seedling. Studying gene expression individual cell types has been challenging due lack spatial information or low throughput existing methods. To overcome these limitations, transcriptomics workflow was developed germinating barley grain. This approach enabled high-throughput analysis expression, revealing specific patterns various functional categories at sub-tissue level. study revealed over 14 000 genes differentially regulated during first 24 h after imbibition. Individual genes, such as aquaporin family, starch degradation, wall modification, transport processes, ribosomal proteins transcription factors, were found have time. Using autocorrelation algorithms, we identified auxin that had increasingly focused within subdomains time, suggesting their role establishing axis. Overall, our provides an unprecedented spatially resolved cellular map germination identifies genomics targets better understand restricted processes germination. The data can be viewed https://spatial.latrobe.edu.au/.

Language: Английский

Citations

25
Unified Mouse and Human Kidney Single-Cell Expression Atlas Reveal Commonalities and Differences in Disease States DOI
Jianfu Zhou, Amin Abedini, Michael S. Balzer

et al.

Journal of the American Society of Nephrology, Journal Year: 2023, Volume and Issue: 34(11), P. 1843 - 1862

Published: Aug. 28, 2023

Mouse models have been widely used to understand kidney disease pathomechanisms and play an important role in drug discovery. However, these not systematically analyzed compared. The authors characterized 18 different mouse at both bulk single-cell gene expression levels compared data from diabetic (DKD) mice patients with DKD. Although single cell-level changes were mostly model-specific, showed similar when a pathway level. also found that fractions of cell types are major drivers differences. the only small overlap between DKD model patients, they observed consistent pathway-level changes.

Language: Английский

Citations

18
Single‐cell RNA sequencing reveals characteristics of myeloid cells in post-acute sequelae of SARS-CoV-2 patients with persistent respiratory symptoms DOI Creative Commons

Hyundong Yoon,

Logan S. Dean,

Boonyanudh Jiyarom

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Although our understanding of the immunopathology and subsequent risk severity COVID-19 disease is evolving, a detailed account immune responses that contribute to long-term consequences pulmonary complications in infection remains unclear. Few studies have cytokine profiles associated with post-acute sequelae SARS-CoV-2 (PASC) persistent symptoms. The dysregulation system drives survivors PASC sufferers largely unknown.

Language: Английский

Citations

6
FAVA: high-quality functional association networks inferred from scRNA-seq and proteomics data DOI Creative Commons
Mikaela Koutrouli, Katerina Nastou, Pau Piera Líndez

et al.

Bioinformatics, Journal Year: 2024, Volume and Issue: 40(2)

Published: Jan. 5, 2024

Protein networks are commonly used for understanding how proteins interact. However, they typically biased by data availability, favoring well-studied with more interactions. To uncover functions of understudied proteins, we must use that not affected this literature bias, such as single-cell RNA-seq and proteomics. Due to sparseness redundancy, functional association analysis becomes complex.

Language: Английский

Citations

6
Aging Atlas Reveals Cell-Type-Specific Regulation of Pro-longevity Strategies DOI Creative Commons
Shihong Max Gao, Yanyan Qi, Qinghao Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 1, 2023

Abstract Organism aging occurs at the multicellular level; however, how pro-longevity mechanisms slow down in different cell types remains unclear. We generated single-cell transcriptomic atlases across lifespan of Caenorhabditis elegans under conditions ( http://mengwanglab.org/atlas ). found cell-specific, age-related changes somatic and germ developed clocks for tissues. These enabled us to determine tissue-specific aging-slowing effects mechanisms, identify major sensitive these regulations. Additionally, we provided a systemic view alternative polyadenylation events types, as well their cell-type-specific during conditions. Together, this study provides molecular insights into they respond strategies.

Language: Английский

Citations

15
Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers DOI Creative Commons
Jan Vincent B. Beltran,

Fang‐Ping Lin,

Chaw‐Liang Chang

et al.

Circulation, Journal Year: 2023, Volume and Issue: 148(22), P. 1778 - 1796

Published: Oct. 31, 2023

Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share similar clinical manifestations, including cardiovascular complications, suggesting underlying immunopathogenic processes. Aberrant neutrophil activation may play a crucial role the shared pathologies of KD MIS-C; however, associated pathogenic mechanisms molecular drivers remain unknown.

Language: Английский

Citations

13
Genome-wide enhancer-associated tandem repeats are expanded in cardiomyopathy DOI Creative Commons
Aleksandra Mitina, Mahreen Khan, Robert Lesurf

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 101, P. 105027 - 105027

Published: Feb. 27, 2024

BackgroundCardiomyopathy is a clinically and genetically heterogeneous heart condition that can lead to failure sudden cardiac death in childhood. While it has strong genetic basis, the aetiology for over 50% of cardiomyopathy cases remains unknown.MethodsIn this study, we analyse characteristics tandem repeats from genome sequence data unrelated individuals diagnosed with Canada United Kingdom (n = 1216) compare them those found general population. We perform burden analysis identify genomic epigenomic features are impacted by rare repeat expansions (TREs), enrichment functional pathways involved TRE-associated genes cardiomyopathy. use Oxford Nanopore targeted long-read sequencing validate size methylation status one most recurrent TREs. also dysregulated tissues cardiomyopathy.FindingsWe demonstrate rarely expanded population predominantly find TREs disproportionately present constrained near transcriptional start sites, have high GC content, frequently overlap active enhancer H3K27ac marks, where expansion-related DNA may reduce gene expression. silencing effect CGG DIP2B through promoter hypermethylation. show enhancer-associated loci highly expressed human cardiomyocytes differentially left ventricle cardiomyopathy.InterpretationOur findings highlight underrecognized contribution risk suggest contribute ∼4% risk.FundingGovernment Ontario (RKCY), The Canadian Institutes Health Research PJT 175329 Azrieli Foundation SickKids Catalyst Scholar Genetics University Toronto McLaughlin Centre (RKCY, SM), Ted Rogers Heart (SM), Data Sciences Institute at 175034 ENP 161429 under frame ERA PerMed (SM, RL), Stroke & Robert M Freedom Chair Cardiovascular Science Bitove Family Professorship Adult Congenital Disease (EO), Innovation (SWS, JR), (PS), Genome (PS, (PS).

Language: Английский

Citations

5
Macrophage-Related Testicular Inflammation in Individuals with Idiopathic Non-Obstructive Azoospermia: A Single-Cell Analysis DOI Open Access
Peng Xia,

Siwei Ouyang,

Rong Shen

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8819 - 8819

Published: May 16, 2023

Male infertility is a global issue that seriously affects reproductive health. This study aimed to understand the underlying causes of idiopathic non-obstructive azoospermia (iNOA), which type male with unknown origins accounts for 10-15% cases. By using single-cell analysis techniques, we uncover mechanisms iNOA and gain insight into cellular molecular changes in testicular environment. In this study, performed bioinformatics scRNA-seq microarray data obtained from GEO database. The included techniques such as pseudotime analysis, cell-cell communication, hdWGCNA. Our showed significant difference between normal groups, indicating disorder spermatogenic microenvironment iNOA. We observed reduction proportion Sertoli cells blocked germ cell differentiation. Additionally, found evidence inflammation related macrophages identified ODF2 CABYR potential biomarkers

Language: Английский

Citations

12