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A Cyclic Permutation Approach to Removing Spatial Dependency between Clustered Gene Ontology Terms.

ABSTRACT: Traditional gene set enrichment analysis falters when applied to large genomic domains, where neighboring genes often share functions. This spatial dependency creates misleading enrichments, mistaking mere physical proximity for genuine biological connections. Here we present Spatial Adjusted Gene Ontology (SAGO), a novel cyclic permutation-based approach, to tackle this challenge. SAGO separates enrichments due to spatial proximity from genuine biological links by incorporating the genes' spatial arrangement into the analysis. We applied SAGO to various datasets in which the identified genomic intervals are large, including replication timing domains, large H3K9me3 and H3K27me3 domains, HiC compartments and lamina-associated domains (LADs). Intriguingly, applying SAGO to prostate cancer samples with large copy number alteration (CNA) domains eliminated most of the enriched GO terms, thus helping to accurately identify biologically relevant gene sets linked to oncogenic processes, free from spatial bias.

SUBMITTER: Rapoport R

PROVIDER: S-EPMC10967837 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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A Cyclic Permutation Approach to Removing Spatial Dependency between Clustered Gene Ontology Terms.

Rapoport Rachel R Greenberg Avraham A Yakhini Zohar Z Simon Itamar I

Biology 20240308 3

Traditional gene set enrichment analysis falters when applied to large genomic domains, where neighboring genes often share functions. This spatial dependency creates misleading enrichments, mistaking mere physical proximity for genuine biological connections. Here we present Spatial Adjusted Gene Ontology (SAGO), a novel cyclic permutation-based approach, to tackle this challenge. SAGO separates enrichments due to spatial proximity from genuine biological links by incorporating the genes' spati ...[more]

PMID: 38534445

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Project description:BackgroundWith the development of high throughput methods of gene analyses, there is a growing need for mining tools to retrieve relevant articles in PubMed. As PubMed grows, literature searches become more complex and time-consuming. Automated search tools with good precision and recall are necessary. We developed GO2PUB to automatically enrich PubMed queries with gene names, symbols and synonyms annotated by a GO term of interest or one of its descendants.ResultsGO2PUB enriches PubMed queries based on selected GO terms and keywords. It processes the result and displays the PMID, title, authors, abstract and bibliographic references of the articles. Gene names, symbols and synonyms that have been generated as extra keywords from the GO terms are also highlighted. GO2PUB is based on a semantic expansion of PubMed queries using the semantic inheritance between terms through the GO graph. Two experts manually assessed the relevance of GO2PUB, GoPubMed and PubMed on three queries about lipid metabolism. Experts' agreement was high (kappa = 0.88). GO2PUB returned 69% of the relevant articles, GoPubMed: 40% and PubMed: 29%. GO2PUB and GoPubMed have 17% of their results in common, corresponding to 24% of the total number of relevant results. 70% of the articles returned by more than one tool were relevant. 36% of the relevant articles were returned only by GO2PUB, 17% only by GoPubMed and 14% only by PubMed. For determining whether these results can be generalized, we generated twenty queries based on random GO terms with a granularity similar to those of the first three queries and compared the proportions of GO2PUB and GoPubMed results. These were respectively of 77% and 40% for the first queries, and of 70% and 38% for the random queries. The two experts also assessed the relevance of seven of the twenty queries (the three related to lipid metabolism and four related to other domains). Expert agreement was high (0.93 and 0.8). GO2PUB and GoPubMed performances were similar to those of the first queries.ConclusionsWe demonstrated that the use of genes annotated by either GO terms of interest or a descendant of these GO terms yields some relevant articles ignored by other tools. The comparison of GO2PUB, based on semantic expansion, with GoPubMed, based on text mining techniques, showed that both tools are complementary. The analysis of the randomly-generated queries suggests that the results obtained about lipid metabolism can be generalized to other biological processes. GO2PUB is available at http://go2pub.genouest.org.

Dataset Information

A Cyclic Permutation Approach to Removing Spatial Dependency between Clustered Gene Ontology Terms.

Publications

A Cyclic Permutation Approach to Removing Spatial Dependency between Clustered Gene Ontology Terms.

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