The reactome pathway knowledgebase 2022

Gillespie, Marc; Jassal, Bijay; Stephan, Ralf; Milacic, Marija; Rothfels, Karen; Senff‐Ribeiro, Andrea; Griss, Johannes; Sevilla, Cristoffer; Matthews, Lisa; Gong, Chuqiao; Chuan, Deng; Varusai, Thawfeek; Ragueneau, Eliot; Haider, Yusra; May, Bruce; Shamovsky, Veronica; Weiser, Joel; Brunson, Timothy; Sanati, Nasim; Beckman, Liam; Shao, Xiang; Fabregat, Antonio; Sidiropoulos, Konstantinos; Murillo, Julieth; Viteri, Guilherme; Cook, Justin; Shorser, Solomon; Bader, Gary D.; Demir, Emek; Sander, Chris; Haw, Robin; Wu, Guanming; Stein, Lincoln; Hermjakob, Henning; D'Eustachio, P

doi:10.1093/nar/gkab1028

Cited by 1,403 publications

(1,152 citation statements)

References 24 publications

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“…In the ‘ Metabolic and signalling pathways ’ section, the popular Reactome database of biological processes and networks has an Update paper ( 46 ) describing an interesting collaboration with the ‘Illuminating the Druggable Genome’ (IDG) consortium ( 47 ) that helps place many ‘dark’ proteins (those that are poorly understood and/or understudied) in the context of Reactome networks. The paper also reports curation of the processes behind SARS-CoV-2 infection, a procedure interestingly expedited by first working on SAR-CoV-1 from March 2020.…”

Section: New and Updated Databasesmentioning

confidence: 99%

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

Rigden

Fernández

2021

Nucleic Acids Research

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The 2022 Nucleic Acids Research Database Issue contains 185 papers, including 87 papers reporting on new databases and 85 updates from resources previously published in the Issue. Thirteen additional manuscripts provide updates on databases most recently published elsewhere. Seven new databases focus specifically on COVID-19 and SARS-CoV-2, including SCoV2-MD, the first of the Issue's Breakthrough Articles. Major nucleic acid databases reporting updates include MODOMICS, JASPAR and miRTarBase. The AlphaFold Protein Structure Database, described in the second Breakthrough Article, is the stand-out in the protein section, where the Human Proteoform Atlas and GproteinDb are other notable new arrivals. Updates from DisProt, FuzDB and ELM comprehensively cover disordered proteins. Under the metabolism and signalling section Reactome, ConsensusPathDB, HMDB and CAZy are major returning resources. In microbial and viral genomes taxonomy and systematics are well covered by LPSN, TYGS and GTDB. Genomics resources include Ensembl, Ensembl Genomes and UCSC Genome Browser. Major returning pharmacology resource names include the IUPHAR/BPS guide and the Therapeutic Target Database. New plant databases include PlantGSAD for gene lists and qPTMplants for post-translational modifications. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). Our latest update to the NAR online Molecular Biology Database Collection brings the total number of entries to 1645. Following last year's major cleanup, we have updated 317 entries, listing 89 new resources and trimming 80 discontinued URLs. The current release is available at http://www.oxfordjournals.org/nar/database/c/.

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Section: New and Updated Databasesmentioning

confidence: 99%

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

Rigden

Fernández

2021

Nucleic Acids Research

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“…Wilcoxon-test instead was used between the allelic fraction of private and shared SNVs in each sample. To perform the SNVs enrichment analysis, we selected all genes harboring at least one deleterious point mutation and performed an over-representation analysis exploiting Reactome Db gene sets collection (121). For each tested PDO, we selected a subset of enriched terms (Q-value < 0.2) and retained those shortlisted in at least 20% of the study samples (relapse samples BLCa112 and BLCa81 excluded, in Table S4 and S5).…”

Section: Deleterious Snvs and Snvs Enrichment Analysismentioning

confidence: 99%

Bladder cancer organoids as a functional system to model different disease stages and therapy response

Minoli

Cantore

Kiener

et al. 2022

Preprint

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Bladder Cancer (BLCa) inter-patient heterogeneity is considered the primary cause of tumor reoccurrence and treatment failure, suggesting that BLCa patients could benefit from a more personalized treatment approach. Patient-derived organoids (PDOs) have been successfully used as a functional model for predicting drug response in different cancer types. In our study, we established BLCa PDO cultures from different BLCa stages. BLCa PDOs preserve the histological and molecular heterogeneity of the parental tumors, including their multiclonal genetic landscapes. BLCa PDOs consistently share key genetic alterations detected in parental tumors, mirroring tumor evolution in longitudinal sampling. Our drug screening pipeline was implemented using BLCa PDOs, testing both standard-of-care and additional FDA-approved compounds for other solid tumors. Integrative analysis of drug response profiles with matched PDO genomic analysis was used to determine enrichment thresholds for candidate markers of therapy resistance and sensitivity. By assessing the clinical history of longitudinally sampled cases, the clonal evolution of the disease could be determined and matched with drug response profiles. In conclusion, we have developed a clinically relevant pipeline for drug response profile assessment and discovery of candidate markers of therapy resistance.

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“…The key genes affected in polymyxin B-treated cells were selected by partial least squaresdiscriminant analysis (PLS-DA). Functional pathway analysis was conducted against the Kyoto Encyclopedia of Genes and Genomes (KEGG) [31] and Reactome hierarchy [32]. The hypergeometric distribution was used to determine whether a pathway was over-presented in the interesting gene list (i.e.…”

Section: Bioinformatic Analysismentioning

confidence: 99%

Polymyxin Induces Significant Transcriptomic Perturbations of Cellular Signalling Networks in Human Lung Epithelial Cells

Azad

Ahmed

et al. 2022

Antibiotics

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Inhaled polymyxins are increasingly used to treat pulmonary infections caused by multidrug-resistant Gram-negative pathogens. We have previously shown that apoptotic pathways, autophagy and oxidative stress are involved in polymyxin-induced toxicity in human lung epithelial cells. In the present study, we employed human lung epithelial cells A549 treated with polymyxin B as a model to elucidate the complex interplay of multiple signalling networks underpinning cellular responses to polymyxin toxicity. Polymyxin B induced toxicity (1.0 mM, 24 h) in A549 cells was assessed by flow cytometry and transcriptomics was performed using microarray. Polymyxin B induced cell death was 19.0 ± 4.2% at 24 h. Differentially expressed genes (DEGs) between the control and polymyxin B treated cells were identified with Student’s t-test. Pathway analysis was conducted with KEGG and Reactome and key hub genes related to polymyxin B induced toxicity were examined using the STRING database. In total we identified 899 DEGs (FDR < 0.01), KEGG and Reactome pathway analyses revealed significantly up-regulated genes related to cell cycle, DNA repair and DNA replication. NF-κB and nucleotide-binding oligomerization domain-like receptor (NOD) signalling pathways were identified as markedly down-regulated genes. Network analysis revealed the top 5 hub genes (i.e., degree) affected by polymyxin B treatment were PLK1(48), CDK20 (46), CCNA2 (42), BUB1 (40) and BUB1B (37). Overall, perturbations of cell cycle, DNA damage and pro-inflammatory NF-κB and NOD-like receptor signalling pathways play key roles in polymyxin-induced toxicity in human lung epithelial cells. Noting that NOD-like receptor signalling represents a group of key sensors for microorganisms and damage in the lung, understanding the mechanism of polymyxin-induced pulmonary toxicity will facilitate the optimisation of polymyxin inhalation therapy in patients.

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The reactome pathway knowledgebase 2022

Cited by 1,403 publications

References 24 publications

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

Bladder cancer organoids as a functional system to model different disease stages and therapy response

Polymyxin Induces Significant Transcriptomic Perturbations of Cellular Signalling Networks in Human Lung Epithelial Cells

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