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PFASUM: a substitution matrix from Pfam structural alignments

Keul, Frank ; Hess, Martin ; Goesele, Michael ; Hamacher, Kay (2017)
PFASUM: a substitution matrix from Pfam structural alignments.
In: BMC Bioinformatics, 2017, 18 (1)
Article, Secondary publication

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Item Type: Article
Type of entry: Secondary publication
Title: PFASUM: a substitution matrix from Pfam structural alignments
Language: English
Date: 27 September 2017
Place of Publication: Darmstadt
Year of primary publication: 2017
Publisher: Biomed Central
Journal or Publication Title: BMC Bioinformatics
Volume of the journal: 18
Issue Number: 1
Corresponding Links:
Origin: Secondary publication via sponsored Golden Open Access


Detecting 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. Results

We 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.


We 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.

URN: urn:nbn:de:tuda-tuprints-65108
Classification DDC: 500 Science and mathematics > 570 Life sciences, biology
Divisions: 10 Department of Biology > Computational Biology and Simulation
Date Deposited: 27 Sep 2017 11:41
Last Modified: 04 Jan 2024 10:30
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/6510
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