Addressing inaccuracies in BLOSUM computation improves homology search performance

BMC Bioinformatics

Research Article

Kay Hamacher¹  Frank Keul¹  Michael Goesele²  Martin Hess³ 

[1]Computational Biology and Simulation, Department of Biology, Technische Universität Darmstadt, Schnittspahnstraße 2, 64287, Darmstadt, Germany

[2]Graphics, Capture and Massively Parallel Computing, Department of Computer Science, Technische Universität Darmstadt, Rundeturmstraße 12, 64283, Darmstadt, Germany

[3]Graphics, Capture and Massively Parallel Computing, Department of Computer Science, Technische Universität Darmstadt, Rundeturmstraße 12, 64283, Darmstadt, Germany

[4]Computational Biology and Simulation, Department of Biology, Technische Universität Darmstadt, Schnittspahnstraße 2, 64287, Darmstadt, Germany

关键词: Substitution matrix;    Homologous sequence search;    BLOSUM;    Correction;    RBLOSUM;    CorBLOSUM;    Performance evaluation;    ASTRAL;    BLOCKS 13+;    BLOCKS 14.3;   

DOI  :  10.1186/s12859-016-1060-3

 received in 2015-11-26, accepted in 2016-04-21,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundBLOSUM matrices belong to the most commonly used substitution matrix series for protein homology search and sequence alignments since their publication in 1992. In 2008, Styczynski et al. discovered miscalculations in the clustering step of the matrix computation. Still, the RBLOSUM64 matrix based on the corrected BLOSUM code was reported to perform worse at a statistically significant level than the BLOSUM62.Here, we present a further correction of the (R)BLOSUM code and provide a thorough performance analysis of BLOSUM-, RBLOSUM- and the newly derived CorBLOSUM-type matrices. Thereby, we assess homology search performance of these matrix-types derived from three different BLOCKS databases on all versions of the ASTRAL20, ASTRAL40 and ASTRAL70 subsets resulting in 51 different benchmarks in total. Our analysis is focused on two of the most popular BLOSUM matrices — BLOSUM50 and BLOSUM62.ResultsOur study shows that fixing small errors in the BLOSUM code results in substantially different substitution matrices with a beneficial influence on homology search performance when compared to the original matrices. The CorBLOSUM matrices introduced here performed at least as good as their BLOSUM counterparts in ∼75 % of all test cases. On up-to-date ASTRAL databases BLOSUM matrices were even outperformed by CorBLOSUM matrices in more than 86 % of the times. In contrast to the study by Styczynski et al., the tested RBLOSUM matrices also outperformed the corresponding BLOSUM matrices in most of the cases. Comparing the CorBLOSUM with the RBLOSUM matrices revealed no general performance advantages for either on older ASTRAL releases. On up-to-date ASTRAL databases however CorBLOSUM matrices performed better than their RBLOSUM counterparts in ∼74 % of the test cases.ConclusionsOur results imply that CorBLOSUM type matrices outperform the BLOSUM matrices on a statistically significant level in most of the cases, especially on up-to-date databases such as ASTRAL ≥2.01. Additionally, CorBLOSUM matrices are closer to those originally intended by Henikoff and Henikoff on a conceptual level. Hence, we encourage the usage of CorBLOSUM over (R)BLOSUM matrices for the task of homology search.

【 授权许可】

CC BY   
© Hess et al. 2016

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