ArticleBioinformatics (Oxford, England)2016
Benchmarking the next generation of homology inference tools.
Article in Bioinformatics (Oxford, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Major advances in protein function assignment by remote homolog detection with protein language models - A review.Current opinion in structural biology · 2025Review
- Protein domain embeddings for fast and accurate similarity search.Genome research · 2024Article
- Advanced computational tools, artificial intelligence and machine-learning approaches in gut microbiota and biomarker identification.Frontiers in medical technology · 2024Review
- Improved global protein homolog detection with major gains in function identification.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Master Blaster: an approach to sensitive identification of remotely related proteins.Scientific reports · 2021Article
- De novo gene birth.PLoS genetics · 2019Article
- MultiDomainBenchmark: a multi-domain query and subject database suite.BMC bioinformatics · 2019Article
- From De Novo to "De Nono": The Majority of Novel Protein-Coding Genes Identified with Phylostratigraphy Are Old Genes or Recent Duplicates.Genome biology and evolution · 2018Article
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
motivationOver the last decades, vast numbers of sequences were deposited in public databases. Bioinformatics tools allow homology and consequently functional inference for these sequences. New profile-based homology search tools have been introduced, allowing reliable detection of remote homologs, but have not been systematically benchmarked. To provide such a comparison, which can guide bioinformatics workflows, we extend and apply our previously developed benchmark approach to evaluate the 'next generation' of profile-based approaches, including CS-BLAST, HHSEARCH and PHMMER, in comparison with the non-profile based search tools NCBI-BLAST, USEARCH, UBLAST and FASTA.
methodWe generated challenging benchmark datasets based on protein domain architectures within either the PFAM + Clan, SCOP/Superfamily or CATH/Gene3D domain definition schemes. From each dataset, homologous and non-homologous protein pairs were aligned using each tool, and standard performance metrics calculated. We further measured congruence of domain architecture assignments in the three domain databases.
resultsCSBLAST and PHMMER had overall highest accuracy. FASTA, UBLAST and USEARCH showed large trade-offs of accuracy for speed optimization.
conclusionProfile methods are superior at inferring remote homologs but the difference in accuracy between methods is relatively small. PHMMER and CSBLAST stand out with the highest accuracy, yet still at a reasonable computational cost. Additionally, we show that less than 0.1% of Swiss-Prot protein pairs considered homologous by one database are considered non-homologous by another, implying that these classifications represent equivalent underlying biological phenomena, differing mostly in coverage and granularity. AVAILABILITY AND IMPLEMENTATION: Benchmark datasets and all scripts are placed at (http://sonnhammer.org/download/Homology_benchmark). CONTACT: forslund@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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