KaKs_Calculator 2.0: A Toolkit Incorporating Gamma-Series Methods and Sliding Window Strategies

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Abstract

We present an integrated stand-alone software package named KaKs_Calculator 2.0 as an updated version. It incorporates 17 methods for the calculation of nonsynonymous and synonymous substitution rates; among them, we added our modified versions of several widely used methods as the gamma series including γ-NG, γ-LWL, γ-MLWL, γ-LPB, γ-MLPB, γ-YN and γ-MYN, which have been demonstrated to perform better under certain conditions than their original forms and are not implemented in the previous version. The package is readily used for the identification of positively selected sites based on a sliding window across the sequences of interests in 5’ to 3’ direction of protein-coding sequences, and have improved the overall performance on sequence analysis for evolution studies. A toolbox, including C++ and Java source code and executable files on both Windows and Linux platforms together with a user instruction, is downloadable from the website for academic purpose at https://sourceforge.net/projects/kakscalculator2/.

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The Bioperl toolkit: Perl modules for the life sciences.

Jason E Stajich, David Block, Kris Boulez … (2002)

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.

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γ-MYN: a new algorithm for estimating Ka and Ks with consideration of variable substitution rates

Da-Peng Wang, Hao-Lei Wan, Song Zhang … (2009)

Background Over the past two decades, there have been several approximate methods that adopt different mutation models and used for estimating nonsynonymous and synonymous substitution rates (Ka and Ks) based on protein-coding sequences across species or even different evolutionary lineages. Among them, MYN method (a Modified version of Yang-Nielsen method) considers three major dynamic features of evolving DNA sequences–bias in transition/transversion rate, nucleotide frequency, and unequal transitional substitution but leaves out another important feature: unequal substitution rates among different sites or nucleotide positions. Results We incorporated a new feature for analyzing evolving DNA sequences–unequal substitution rates among different sites–into MYN method, and proposed a modified version, namely γ (gamma)-MYN, based on an assumption that the evolutionary rate at each site follows a mode of γ-distribution. We applied γ-MYN to analyze the key estimator of selective pressure ω (Ka/Ks) and other relevant parameters in comparison to two other related methods, YN and MYN, and found that neglecting the variation of substitution rates among different sites may lead to biased estimations of ω. Our new method appears to have minimal deviations when relevant parameters vary within normal ranges defined by empirical data. Conclusion Our results indicate that unequal substitution rates among different sites have variable influences on ω under different evolutionary rates while both transition/transversion rate ratio and unequal nucleotide frequencies affect Ka and Ks thus selective pressure ω. Reviewers This paper was reviewed by Kateryna Makova, David A. Liberles (nominated by David H Ardell), Zhaolei Zhang (nominated by Mark Gerstein), and Shamil Sunyaev.

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Correlation between Ka/Ks and Ks is related to substitution model and evolutionary lineage.

Gane Wong, Ya-Jun Li, Lu-Jun Yu … (2009)

In 2005, Wyckoff and coworkers described a surprisingly strong correlation between Ka/Ks and Ks in several data sets using the LPB93 algorithm. This finding indicated the possibility of a paradigm shift in the way selection strength can be measured using the Ka/Ks ratio. We carried out a calculation of Ka and Ks using six different algorithms on three cross-species orthologous data sets and found a highly variable correlation among the algorithms and lineages. Algorithms based on the GY-HKY substitution model exhibit a weaker positive correlation or a stronger negative correlation than those based on the K2P and JC69 substitution model. Even if one algorithm shows a positive correlation between Ka/Ks and Ks in a warm-blooded lineage, it may show no correlation in a cold-blooded lineage. This algorithm-related and evolutionary lineage-related correlation indicates the need for great caution in drawing conclusions when using only one Ka and Ks algorithm in a genomewide analysis of selection strength. Our results indicated that currently used algorithms for Ka and Ks calculations are flawed and need improvements.

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Author and article information

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Jun Yu

Journal

Journal ID (nlm-ta): Genomics Proteomics Bioinformatics

Journal ID (iso-abbrev): Genomics Proteomics Bioinformatics

Title: Genomics, Proteomics & Bioinformatics

Publisher: Elsevier

ISSN (Print): 1672-0229

ISSN (Electronic): 2210-3244

Publication date PMC-release: 05 May 2010

Publication date (Print): March 2010

Publication date (Electronic): 05 May 2010

Volume: 8

Issue: 1

Pages: 77-80

Affiliations

[1 ]CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China

[2 ]Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China

[3 ]Graduate University of Chinese Academy of Sciences, Beijing 100049, China

[4 ]Plant Stress Genomics Research Center, Division of Chemical and Life Sciences & Engineering, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia

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[* ]Corresponding author. junyu@ 123456big.ac.cn

[#]

Equal contribution.

Article

Publisher ID: S1672-0229(10)60008-3

DOI: 10.1016/S1672-0229(10)60008-3

PMC ID: 5054116

PubMed ID: 20451164

SO-VID: b6392ee1-1324-43db-a37e-52fdb9c9b085

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This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).

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KaKs_Calculator 2.0: A Toolkit Incorporating Gamma-Series Methods and Sliding Window Strategies

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Most cited references 9

The Bioperl toolkit: Perl modules for the life sciences.

γ-MYN: a new algorithm for estimating Ka and Ks with consideration of variable substitution rates

Correlation between Ka/Ks and Ks is related to substitution model and evolutionary lineage.

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