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. 2019 Nov 14;20(1):238.
doi: 10.1186/s13059-019-1832-y.

OrthoFinder: phylogenetic orthology inference for comparative genomics

David M Emms  1 , Steven Kelly  2
Affiliations

Affiliations

  • 1 Department of Plant Sciences, University of Oxford, South Parks Road, Oxford, OX1 3RB, UK.
  • 2 Department of Plant Sciences, University of Oxford, South Parks Road, Oxford, OX1 3RB, UK. steven.kelly@plants.ox.ac.uk.

OrthoFinder: phylogenetic orthology inference for comparative genomics

David M Emms et al. Genome Biol. .
. 2019 Nov 14;20(1):238.
doi: 10.1186/s13059-019-1832-y.

Authors

David M Emms  1 , Steven Kelly  2

Affiliations

  • 1 Department of Plant Sciences, University of Oxford, South Parks Road, Oxford, OX1 3RB, UK.
  • 2 Department of Plant Sciences, University of Oxford, South Parks Road, Oxford, OX1 3RB, UK. steven.kelly@plants.ox.ac.uk.

Abstract

Here, we present a major advance of the OrthoFinder method. This extends OrthoFinder's high accuracy orthogroup inference to provide phylogenetic inference of orthologs, rooted gene trees, gene duplication events, the rooted species tree, and comparative genomics statistics. Each output is benchmarked on appropriate real or simulated datasets, and where comparable methods exist, OrthoFinder is equivalent to or outperforms these methods. Furthermore, OrthoFinder is the most accurate ortholog inference method on the Quest for Orthologs benchmark test. Finally, OrthoFinder's comprehensive phylogenetic analysis is achieved with equivalent speed and scalability to the fastest, score-based heuristic methods. OrthoFinder is available at https://github.com/davidemms/OrthoFinder.

Keywords: Comparative genomics; Gene duplication; Gene tree inference; Ortholog inference.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Fig. 1

Pairwise similarity score-based ortholog inference…

Fig. 1

Pairwise similarity score-based ortholog inference can be misled by variable sequence evolution rates. …

Fig. 1
Pairwise similarity score-based ortholog inference can be misled by variable sequence evolution rates. a Phylogenetic tree of a typical gene family. The correct orthologs of species A-gene 1 are not identified. b Species A-gene 2 is misidentified as the ortholog of the genes from species B and C. Left-hand side: gene trees with branches to scale and the true orthology relationships, which can be determined from the gene tree. Right-hand side: Reciprocal best hits (RBH) based on gene similarity scores that are monotonic with branch length and the orthology relationships inferred from these scores using standard heuristics (orthologs inferred using RBHs and co-orthology identified from within species hits better than closest RBH [8, 16]). FP, false positive; FN, false negative
Fig. 2

Fig. 2

The OrthoFinder workflow. The method…

Fig. 2

The OrthoFinder workflow. The method used for each step is shown by the…

Fig. 2
The OrthoFinder workflow. The method used for each step is shown by the arrow. Published algorithms are shown in italics and are followed by an asterisk. A dotted blue line connecting with a solid arrow indicates additional data that are used in order to carry out the transformation indicated by the solid arrow. MSA, multiple sequence alignment-based tree inference; DLC, duplication-loss-coalescence. (a) Orthogroup inference using the original OrthoFinder algorithm (an orthogroup is the set of genes descended from a single gene in the last common ancestor of all the species under consideration). (b) Gene tree inference. (c) Species tree inference. (d) Species tree rooting (e) Gene tree rooting (f) Hybrid overlap + DLC analysis of rooted gene trees to infer orthologs and gene duplication events. (g) Illustration of the ortholog results table for the genes in each input species (four main boxes). The horizontal divisions within these show the orthologs for each individual species pair. (h) Illustration of the gene duplication event table showing the location of the gene duplication events mapped to the species tree, the location in the gene tree, the percent retention of the duplicate genes in the sampled species, and the genes descended from the gene duplication event. (i) Comparative genomics statistics
Fig. 3

Fig. 3

Summary of OrthoFinder analysis of…

Fig. 3

Summary of OrthoFinder analysis of a set of Chordata species: Ciona intestinalis , …

Fig. 3
Summary of OrthoFinder analysis of a set of Chordata species: Ciona intestinalis, Danio rerio, Oryzias latipes, Xenopus tropicalis, Gallus gallus, Monodelphis domestica, Mus musculus, Rattus norvegicus, Pan troglodytes, and Homo sapiens. Bar charts and heat map contain data for each species, aligned to the corresponding species in the tree in a. a The species tree inferred by STAG and rooted by STRIDE. b Percentage of genes from each species assigned to orthogroups. c The number of species-specific orthogroups. d The number of genes with orthologs in any/all species. e Heat map of the number of orthogroups containing each species pair (top right) and orthologs between each species (bottom left). f Ortholog multiplicities for two species, C. intestinalis and H. sapiens, with respect to all other species. g The number of gene duplication events on each terminal branch of the species tree. h The number of duplications on each branch of the species tree and retained in all descendant species. OG, orthogroup; sp., species; spp., species (plural); dups., gene duplication events
Fig. 4

Fig. 4

a – l Quest for…

Fig. 4

a – l Quest for Orthologs 2011_04 benchmarks (see [1]) on 66 species…
Fig. 4
a–l Quest for Orthologs 2011_04 benchmarks (see [1]) on 66 species across Eukarya, Bacteria and Archaea for ortholog inference methods. Dotted line shows Pareto frontier. Data for graphs are in Additional file 1: Table S1. a, b F-score on SwissTree and TreeFam-A tests. c “Pseudo-F-score” across the two Species Tree Discordance Tests (STDT). d “Pseudo-F-score” across the four Generalized Species Tree Discordance Tests (GSTDT). e–f Agreement of orthologs SwissTree/FreeFam-A trees g-h Benchmarks across the STDT & GSTDT. X-axis: Total fraction of randomly selected genes with predicted orthologs in a predefined set of species for the two STDTs & four GSTDTs respectively. Y-axis: Average (1 – normalised Robinson-Foulds distance) between gene tree for putative orthologs and the known species tree across the two STDT & four GSTD respectively. The four individual GSTDTs and two individual STDTs are shown in Additional file: 1 i-l Zoom in of plots e-h. See Methods section “Ortholog Benchmarking” for details of Quest for Orthologs benchmarks. m Runtime for each method with 4-256 input Fungi proteomes. n Results returned by methods, a multi-species orthogroup is the set of genes descended from a single gene in the last common ancestor of three or more species
Fig. 5

Fig. 5

a Duplication F-score, on simulated…

Fig. 5

a Duplication F-score, on simulated gene trees. b Runtime to analyse all trees…
Fig. 5
a Duplication F-score, on simulated gene trees. b Runtime to analyse all trees from the 4 to 128 species Fungi datasets (see Methods), a maximum time of 120 hours (4.3x10 seconds) was allowed. DLCpar (full) did not complete the smallest dataset in this time limit and so only the lower bound for the first time point is shown. c-d Precision and recall
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