FB2024_02 , released April 23, 2024
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Gene Ontology Curators, (2002-). Gene Ontology Curators, (2002-). Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.  ( Link 1 )
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FBrf0255270
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Personal communication to FlyBase
Abstract
In the course of gene function analysis, Gene Ontology (GO) terms are assigned to genes on the basis of sequence similarity to homologous sequences using the evidence code 'inferred from sequence or structural similarity' (ISS). Following the rules established by the GO reference genome project, it is mandatory to include a database cross-reference in the GO annotation that identifies the similar gene/gene product. To avoid circular inferences, the similar gene must be experimentally characterised; the GO term should only be assigned if the similar gene can be annotated with the same term (or a more specific child term) using an experimental evidence code (inferred from direct assay, IDA; inferred from mutant phenotype, IMP; inferred from genetic interaction, IGI, inferred from physical interaction, IPI; inferred from expression pattern, IEP). Homologous sequences are identified by computational sequence analysis and the significance of matches judged on a case-by-case basis by the GO curator.
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Text of Personal Communication
Method for transferring manual annotations to an entry based on a curator's judgment of its similarity to a putative ortholog that has annotations that are supported with experimental evidence. Annotations are created when a curator judges that the sequence of a protein shows high similarity to another protein that has annotation(s) supported by experimental evidence (and therefore display one of the evidence codes EXP, IDA, IGI, IMP, IPI or IEP). Annotations resulting from the transfer of GO terms display the 'ISS' evidence code and include an accession for the protein from which the annotation was projected in the 'with' field (column 8). This field can contain either a UniProtKB accession or an IPI (International Protein Index) identifier. Only annotations with an experimental evidence code and which do not have the 'NOT' qualifier are transferred. Putative orthologs are chosen using information combined from a variety of complementary sources. Potential orthologs are initially identified using sequence similarity search programs such as BLAST. Orthology relationships are then verified manually using a combination of resources including sequence analysis tools, phylogenetic and comparative genomics databases such as Ensembl Compara, INPARANOID and OrthoMCL, as well as other specialised databases such as species-specific collections (e.g. HGNC's HCOP). In all cases curators check each alignment and use their experience to assess whether similarity is considered to be strong enough to infer that the two proteins have a common function so that they can confidently project an annotation. While there is no fixed cut-off point in percentage sequence similarity, generally proteins which have greater than 30% identity that covers greater than 80% of the length of both proteins are examined further. For mammalian proteins this cut-off tends to be higher, with an average of 80% identity over 90% of the length of both proteins. Strict orthologs are desirable but not essential. In general, when there is evidence of multiple paralogs for a single species, annotations using less specific GO terms are transferred to the paralogs, however, annotations using more specific GO terms may be transferred to the most similar paralog in each species, this decision is taken on a case by case basis and may be influenced by statements by researchers in the field. Further detailed information on this procedure can be found at: https://wiki.geneontology.org/index.php/Inferred_from_Sequence_or_structural_Similarity_(ISS).
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This reference corresponds to annotations made to GO_REF:0000024 .

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    English
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