Efficient gene orthology inference via large-scale rearrangements

Background Recently we developed a gene orthology inference tool based on genome rearrangements ( Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal...

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Vydané v:Algorithms for molecular biology Ročník 18; číslo 1; s. 1 - 18
Hlavní autori: Rubert, Diego P., Braga, Marília D. V.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London BioMed Central 28.09.2023
BioMed Central Ltd
Springer Nature B.V
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Abstract Background Recently we developed a gene orthology inference tool based on genome rearrangements ( Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space. Results In this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into m ≥ 1 subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to F L Y B A S E families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with F L Y B A S E , when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the M C L algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with M C L . Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at https://gitlab.ub.uni-bielefeld.de/gi/FFGC or as a Conda package at https://anaconda.org/bioconda/ffgc .
AbstractList BackgroundRecently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space.ResultsIn this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into \(m\ge 1\) subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to \({\text{F}} {\textsc{ly}} {\text{B}} {\textsc{ase}}\) families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with \({\text{F}} {\textsc{ly}} {\text{B}} {\textsc{ase}}\), when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the \({\textsc{mcl}}\) algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with \(\textsc {mcl}\). Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at https://gitlab.ub.uni-bielefeld.de/gi/FFGC or as a Conda package at https://anaconda.org/bioconda/ffgc.
Recently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space. In this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into [formula omitted] subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to [formula omitted] families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with [formula omitted], when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the [formula omitted] algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with [formula omitted]. Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at https://gitlab.ub.uni-bielefeld.de/gi/FFGC or as a Conda package at https://anaconda.org/bioconda/ffgc.
Background Recently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space. Results In this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into [formula omitted] subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to [formula omitted] families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with [formula omitted], when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the [formula omitted] algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with [formula omitted]. Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at Keywords: Comparative genomics, Double-cut-and-join, Indels, Gene orthology
Background Recently we developed a gene orthology inference tool based on genome rearrangements ( Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space. Results In this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into m ≥ 1 subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to F L Y B A S E families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with F L Y B A S E , when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the M C L algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with M C L . Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at https://gitlab.ub.uni-bielefeld.de/gi/FFGC or as a Conda package at https://anaconda.org/bioconda/ffgc .
Abstract Background Recently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space. Results In this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into $$m\ge 1$$ m ≥ 1 subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to $${\text{F}} {\textsc{ly}} {\text{B}} {\textsc{ase}}$$ F L Y B A S E families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with $${\text{F}} {\textsc{ly}} {\text{B}} {\textsc{ase}}$$ F L Y B A S E , when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the $${\textsc{mcl}}$$ M C L algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with $$\textsc {mcl}$$ M C L . Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at https://gitlab.ub.uni-bielefeld.de/gi/FFGC or as a Conda package at https://anaconda.org/bioconda/ffgc .
Recently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space.BACKGROUNDRecently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a set of genomes our method first computes all pairwise gene similarities. Then it runs pairwise ILP comparisons to compute optimal gene matchings, which minimize, by taking the similarities into account, the weighted rearrangement distance between the analyzed genomes (a problem that is NP-hard). The gene matchings are then integrated into gene families in the final step. The mentioned ILP includes an optimal capping that connects each end of a linear segment of one genome to an end of a linear segment in the other genome, producing an exponential increase of the search space.In this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into [Formula: see text] subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to [Formula: see text] families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with [Formula: see text], when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the [Formula: see text] algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with [Formula: see text]. Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at https://gitlab.ub.uni-bielefeld.de/gi/FFGC or as a Conda package at https://anaconda.org/bioconda/ffgc .RESULTSIn this work, we design and implement a heuristic capping algorithm that replaces the optimal capping by clustering (based on their gene content intersections) the linear segments into [Formula: see text] subsets, whose ends are capped independently. Furthermore, in each subset, instead of allowing all possible connections, we let only the ends of content-related segments be connected. Although there is no guarantee that m is much bigger than one, and with the possible side effect of resulting in sub-optimal instead of optimal gene matchings, the heuristic works very well in practice, from both the speed performance and the quality of computed solutions. Our experiments on primate and fruit fly genomes show two positive results. First, for complete assemblies of five primates the version with heuristic capping reports orthologies that are very similar to the orthologies computed by the version of our tool with optimal capping. Second, we were able to efficiently analyze fruit fly genomes with incomplete assemblies distributed in hundreds or even thousands of contigs, obtaining gene families that are very similar to [Formula: see text] families. Indeed, our tool inferred a higher number of complete cliques, with a higher intersection with [Formula: see text], when compared to gene families computed by other inference tools. We added a post-processing for refining, with the aid of the [Formula: see text] algorithm, our ambiguous families (those with more than one gene per genome), improving even more the accuracy of our results. Our approach is implemented into a pipeline incorporating the pre-computation of gene similarities and the post-processing refinement of ambiguous families with [Formula: see text]. Both the original version with optimal capping and the new modified version with heuristic capping can be downloaded, together with their detailed documentations, at https://gitlab.ub.uni-bielefeld.de/gi/FFGC or as a Conda package at https://anaconda.org/bioconda/ffgc .
ArticleNumber 14
Audience Academic
Author Rubert, Diego P.
Braga, Marília D. V.
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Issue 1
Keywords Comparative genomics
Double-cut-and-join
Indels
Gene orthology
Language English
License Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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PublicationTitle Algorithms for molecular biology
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Snippet Background Recently we developed a gene orthology inference tool based on genome rearrangements ( Journal of Bioinformatics and Computational Biology 19:6,...
Background Recently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6,...
Recently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6, 2021). Given a...
BackgroundRecently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology 19:6,...
Abstract Background Recently we developed a gene orthology inference tool based on genome rearrangements (Journal of Bioinformatics and Computational Biology...
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SubjectTerms Algorithms
Analysis
Animal genetics
Assemblies
Bioinformatics
Biomedical and Life Sciences
Capping
Cellular and Medical Topics
Chromosomes
Clustering
Comparative genomics
Computation
Computational Biology/Bioinformatics
Double-cut-and-join
Fruit flies
Fruits
Gene families
Gene orthology
Genes
Genetic research
Genomes
Genomics
Heuristic
Indels
Inference
Life Sciences
Orthology
Physiological
Problem solving
Segments
Selected papers from WABI 2022
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Title Efficient gene orthology inference via large-scale rearrangements
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