PFASUM: a substitution matrix from Pfam structural alignments

BMC Bioinformatics

Research Article

Frank Keul¹  Kay Hamacher¹  Michael Goesele²  Martin Hess² 

[1] Computational Biology and Simulation, Department of Biology, Technische Universität Darmstadt, Schnittspahnstraße 2, 64287, Darmstadt, Germany;Graphics, Capture and Massively Parallel Computing, Department of Computer Science, Technische Universität Darmstadt, Rundeturmstraße 12, 64283, Darmstadt, Germany;

关键词: Substitution matrix;    PFASUM;    Homologous sequence search;    Sequence alignment;   

DOI  :  10.1186/s12859-017-1703-z

 received in 2017-03-01, accepted in 2017-05-22,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundDetecting homologous protein sequences and computing multiple sequence alignments (MSA) are fundamental tasks in molecular bioinformatics. These tasks usually require a substitution matrix for modeling evolutionary substitution events derived from a set of aligned sequences. Over the last years, the known sequence space increased drastically and several publications demonstrated that this can lead to significantly better performing matrices. Interestingly, matrices based on dated sequence datasets are still the de facto standard for both tasks even though their data basis may limit their capabilities.We address these aspects by presenting a new substitution matrix series called PFASUM. These matrices are derived from Pfam seed MSAs using a novel algorithm and thus build upon expert ground truth data covering a large and diverse sequence space.ResultsWe show results for two use cases: First, we tested the homology search performance of PFASUM matrices on up-to-date ASTRAL databases with varying sequence similarity. Our study shows that the usage of PFASUM matrices can lead to significantly better homology search results when compared to conventional matrices. PFASUM matrices with comparable relative entropies to the commonly used substitution matrices BLOSUM50, BLOSUM62, PAM250, VTML160 and VTML200 outperformed their corresponding counterparts in 93% of all test cases. A general assessment also comparing matrices with different relative entropies showed that PFASUM matrices delivered the best homology search performance in the test set.Second, our results demonstrate that the usage of PFASUM matrices for MSA construction improves their quality when compared to conventional matrices. On up-to-date MSA benchmarks, at least 60% of all MSAs were reconstructed in an equal or higher quality when using MUSCLE with PFASUM31, PFASUM43 and PFASUM60 matrices instead of conventional matrices. This rate even increases to at least 76% for MSAs containing similar sequences.ConclusionsWe present the novel PFASUM substitution matrices derived from manually curated MSA ground truth data covering the currently known sequence space. Our results imply that PFASUM matrices improve homology search performance as well as MSA quality in many cases when compared to conventional substitution matrices. Hence, we encourage the usage of PFASUM matrices and especially PFASUM60 for these specific tasks.

【 授权许可】

CC BY   
© The Author(s) 2017

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