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An expanded evaluation of protein function prediction methods shows an improvement in accuracy

View Article: PubMed Central - PubMed

ABSTRACT

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging.

Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2.

Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent.

Electronic supplementary material: The online version of this article (doi:10.1186/s13059-016-1037-6) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

CAFA2 benchmark breakdown. a The benchmark size for each of the four ontologies. b Breakdown of benchmarks for both types over 11 species (with no less than 15 proteins) sorted according to the total number of benchmark proteins. For both panels, dark colors (blue, red, and yellow) correspond to no-knowledge (NK) types, while their light color counterparts correspond to limited-knowledge (LK) types. The distributions of information contents corresponding to the benchmark sets are shown in Additional file 1. The size of CAFA 1 benchmarks are shown in gray. BPO Biological Process Ontology, CCO Cellular Component Ontology, HPO Human Phenotype Ontology, LK limited-knowledge, MFO Molecular Function Ontology, NK no-knowledge
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Fig2: CAFA2 benchmark breakdown. a The benchmark size for each of the four ontologies. b Breakdown of benchmarks for both types over 11 species (with no less than 15 proteins) sorted according to the total number of benchmark proteins. For both panels, dark colors (blue, red, and yellow) correspond to no-knowledge (NK) types, while their light color counterparts correspond to limited-knowledge (LK) types. The distributions of information contents corresponding to the benchmark sets are shown in Additional file 1. The size of CAFA 1 benchmarks are shown in gray. BPO Biological Process Ontology, CCO Cellular Component Ontology, HPO Human Phenotype Ontology, LK limited-knowledge, MFO Molecular Function Ontology, NK no-knowledge

Mentions: Figure 2 summarizes the benchmarks we used in this study. Figure 2a shows the benchmark sizes for each of the ontologies and compares these numbers to CAFA1. All species that have at least 15 proteins in any of the benchmark categories are listed in Fig. 2b.Fig. 2


An expanded evaluation of protein function prediction methods shows an improvement in accuracy
CAFA2 benchmark breakdown. a The benchmark size for each of the four ontologies. b Breakdown of benchmarks for both types over 11 species (with no less than 15 proteins) sorted according to the total number of benchmark proteins. For both panels, dark colors (blue, red, and yellow) correspond to no-knowledge (NK) types, while their light color counterparts correspond to limited-knowledge (LK) types. The distributions of information contents corresponding to the benchmark sets are shown in Additional file 1. The size of CAFA 1 benchmarks are shown in gray. BPO Biological Process Ontology, CCO Cellular Component Ontology, HPO Human Phenotype Ontology, LK limited-knowledge, MFO Molecular Function Ontology, NK no-knowledge
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC5015320&req=5

Fig2: CAFA2 benchmark breakdown. a The benchmark size for each of the four ontologies. b Breakdown of benchmarks for both types over 11 species (with no less than 15 proteins) sorted according to the total number of benchmark proteins. For both panels, dark colors (blue, red, and yellow) correspond to no-knowledge (NK) types, while their light color counterparts correspond to limited-knowledge (LK) types. The distributions of information contents corresponding to the benchmark sets are shown in Additional file 1. The size of CAFA 1 benchmarks are shown in gray. BPO Biological Process Ontology, CCO Cellular Component Ontology, HPO Human Phenotype Ontology, LK limited-knowledge, MFO Molecular Function Ontology, NK no-knowledge
Mentions: Figure 2 summarizes the benchmarks we used in this study. Figure 2a shows the benchmark sizes for each of the ontologies and compares these numbers to CAFA1. All species that have at least 15 proteins in any of the benchmark categories are listed in Fig. 2b.Fig. 2

View Article: PubMed Central - PubMed

ABSTRACT

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging.

Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2.

Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent.

Electronic supplementary material: The online version of this article (doi:10.1186/s13059-016-1037-6) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus