Multiscale community detection in Cytoscape

Singhal, Akshat; Cao, Song; Churas, Christopher; Pratt, Dexter; Fortunato, Santo; Zheng, Fan; Ideker, Trey

doi:10.1371/journal.pcbi.1008239

Cited by 42 publications

(31 citation statements)

References 36 publications

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“…with the following criteria: Algorithm: OSLOM, weight column: STRING score, random number seed: 1, and all other settings at default. Then, we performed functional enrichment on the hierarchy network using g: Profiler as the algorithm ( 31 ).…”

Section: Methodsmentioning

confidence: 99%

Combined Transcriptome and Proteome Leukocyte’s Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis

et al. 2021

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Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in “omics” technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co‐differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down‐regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up‐regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host‐defense system.

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Section: Methodsmentioning

confidence: 99%

Combined Transcriptome and Proteome Leukocyte’s Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis

et al. 2021

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“…First, significantly changed genes in Foz/Foz WD week 12 compared with WT chow week 12 (adjusted P < .05, absolute value [log fold change], >1.5) were integrated with high confidence interactions from STRING (edge score, >0.7). The resulting network was input to the CDAPS (Community Detection Application and Service) hierarchical clustering tool 46 in Cytoscape (Institute for Systems Biology, 2019, https://www.cytoscape.org .) 47 to identify biological pathways underlying the Foz/Foz WD phenotype.…”

Section: Methodsmentioning

confidence: 99%

“…[log fold change], >1.5) were integrated with high confidence interactions from STRING (edge score, >0.7). The resulting network was input to the CDAPS hierarchical clustering tool 46 in Cytoscape Q44 47 to identify biological pathways underlying the Foz/Foz WD phenotype. We used the OSLOM clustering algorithm available in CDAPS.…”

Section: Rna Sequencingmentioning

confidence: 99%

Nonalcoholic Steatohepatitis and HCC in a Hyperphagic Mouse Accelerated by Western Diet

Ganguly

Muench

Shang

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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This study establishes a relevant mouse model of nonalcoholic steatohepatitis-fibrosis-hepatocellular carcinoma that closely recapitulates human disease. With this model, we elucidate multitissue dynamics of nonalcoholic steatohepatitis/hepatocellular carcinoma progression, as well as regression. We define the key signaling and cytokine pathways that are critical for disease development and resolution.BACKGROUND & AIMS: How benign liver steatosis progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC) remains elusive. NASH progression entails diverse pathogenic mechanisms and relies on complex cross-talk between multiple tissues such as the gut, adipose tissues, liver, and the brain. Using a hyperphagic mouse fed with a Western diet (WD), we aimed to elucidate the cross-talk and kinetics of hepatic and extrahepatic alterations during NASH-HCC progression, as well as regression.METHODS: Hyperphagic mice lacking a functional Alms1 gene (Foz/Foz) and wild-type littermates were fed WD or standard chow for 12 weeks for NASH/fibrosis and for 24 weeks for HCC development. NASH regression was modeled by switching back to normal chow after NASH development.RESULTS: FozþWD mice were steatotic within 1 to 2 weeks, developed NASH by 4 weeks, and grade 3 fibrosis by 12 weeks, accompanied by chronic kidney injury. FozþWD mice that continued on WD progressed to cirrhosis and HCC within 24 weeks and had reduced survival as a result of cardiac dysfunction. However, NASH mice that were switched to normal chow showed NASH regression, improved survival, and did not develop HCC. Transcriptomic and histologic analyses of Foz/Foz NASH liver showed strong concordance with human NASH. NASH was preceded by an early disruption of gut barrier, microbial dysbiosis, lipopolysaccharide leakage, and intestinal inflammation. This led to acute-phase liver inflammation in FozþWD mice, characterized by neutrophil infiltration and increased levels of several chemokines/cytokines. The liver cytokine/chemokine profile evolved as NASH progressed, with subsequent predominance by monocyte recruitment. CONCLUSIONS:The FozþWD model closely mimics the pathobiology and gene signature of human NASH with fibrosis and subsequent HCC. FozþWD mice provide a robust and

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“…HiDeF is available through CDAPS (Community Detection APplication and Service) [55], which enables simultaneous visualization of the hierarchical model and the underlying network data and is integrated with the Cytoscape visualization and analysis environment. The Cytoscape App can be downloaded at: http://apps.cytoscape.org/apps/ cycommunitydetection.…”

Section: Protein-protein Interaction Networkmentioning

confidence: 99%

HiDeF: identifying persistent structures in multiscale ‘omics data

et al. 2021

Self Cite

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In any ‘omics study, the scale of analysis can dramatically affect the outcome. For instance, when clustering single-cell transcriptomes, is the analysis tuned to discover broad or specific cell types? Likewise, protein communities revealed from protein networks can vary widely in sizes depending on the method. Here, we use the concept of persistent homology, drawn from mathematical topology, to identify robust structures in data at all scales simultaneously. Application to mouse single-cell transcriptomes significantly expands the catalog of identified cell types, while analysis of SARS-COV-2 protein interactions suggests hijacking of WNT. The method, HiDeF, is available via Python and Cytoscape.

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Multiscale community detection in Cytoscape

Cited by 42 publications

References 36 publications

Combined Transcriptome and Proteome Leukocyte’s Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis

Combined Transcriptome and Proteome Leukocyte’s Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis

Nonalcoholic Steatohepatitis and HCC in a Hyperphagic Mouse Accelerated by Western Diet

HiDeF: identifying persistent structures in multiscale ‘omics data

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