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The identification of orthologs—genes in different species which descended from the same gene in their last common ancestor—is a prerequisite for many analyses in comparative genomics and molecular evolution. Numerous algorithms and resources have been conceived to address this problem, but benchmarking and interpreting them is fraught with difficulties (need to compare them on a common input dataset, absence of ground truth, computational cost of calling orthologs). To address this, the Quest for Orthologs consortium maintains a reference set of proteomes and provides a web server for continuous orthology benchmarking (http://orthology.benchmarkservice.org). Furthermore, consensus ortholog calls derived from public benchmark submissions are provided on the Alliance of Genome Resources website, the joint portal of NIH-funded model organism databases. ; Service and Infrastructure grant from the Swiss Institute of Bioinformatics [to C.D.]; NSF [1917302 to P.D.T.]; NIH NHGRI [HG002273, HG010859 to P.D.T.]; INB [PT17/0009/0001 - ISCIII-SGEFI/ERDF to J.G.V., V.S., J.M.F., L.C., J.L.G. and S.C.G.]; H2020 ELIXIR-EXCELERATE [676559 to J.G.V., V.S., J.M.F., L.C., J.L.G. and S.C.G]; ELIXIR, the research infrastructure for life-science data [to J.G.V., V.S., J.M.F., L.C., J.L.G. and S.C.G]; Ministerio de Ciencia, Innovación y Universidades [PGC2018-098073-A-I00 MCIU/AEI/FEDER, UE to J.H.C.]; European Union's Horizon 2020 Research and Innovation Programme [686070 to J.H.C. and D.S, and 637765 to D.M.E. and S.K.]; Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid and Fondo Social Europeo [PEJ-2017-AI/TIC-7514 to A.H.P.]; IdEX Unistra in the framework of the Investments for the future program of the French government [to O.L.]; National Institutes of Health (NIH) [U24HG007822 to M.J.M.]; European Molecular Biology Laboratory (EMBL) [core funds to M.J.M and M.M.]; Wellcome Trust [WT108749/Z/15/Z to M.M.]; S.K. is a royal Society University Research Fellow; Swiss National Science Foundation [183723 to C.D.]. Funding for open access charge: Swiss National Science Foundation. ; Peer Reviewed ; Postprint (published version)

8 Pág. ; The Quest for Orthologs Consortium ; The identification of orthologs-genes in different species which descended from the same gene in their last common ancestor-is a prerequisite for many analyses in comparative genomics and molecular evolution. Numerous algorithms and resources have been conceived to address this problem, but benchmarking and interpreting them is fraught with difficulties (need to compare them on a common input dataset, absence of ground truth, computational cost of calling orthologs). To address this, the Quest for Orthologs consortium maintains a reference set of proteomes and provides a web server for continuous orthology benchmarking (http://orthology.benchmarkservice.org). Furthermore, consensus ortholog calls derived from public benchmark submissions are provided on the Alliance of Genome Resources website, the joint portal of NIH-funded model organism databases. ; Service and Infrastructure grant from the Swiss Institute of Bioinformatics [to C.D.]; NSF [1917302 to P.D.T.]; NIH NHGRI [HG002273, HG010859 to P.D.T.]; INB [PT17/0009/0001 - ISCIII-SGEFI/ERDF to J.G.V., V.S., J.M.F., L.C., J.L.G. and S.C.G.]; H2020 ELIXIR-EXCELERATE [676559 to J.G.V., V.S., J.M.F., L.C., J.L.G. and S.C.G]; ELIXIR, the research infrastructure for life-science data [to J.G.V., V.S., J.M.F., L.C., J.L.G. and S.C.G]; Ministerio de Ciencia, Innovación y Universidades [PGC2018-098073-A-I00 MCIU/AEI/FEDER, UE to J.H.C.]; European Union's Horizon 2020 Research and Innovation Programme [686070 to J.H.C. and D.S, and 637765 to D.M.E. and S.K.]; Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid and Fondo Social Europeo [PEJ-2017-AI/TIC-7514 to A.H.P.]; IdEX Unistra in the framework of the Investments for the future program of the French government [to O.L.]; National Institutes of Health (NIH) [U24HG007822 to M.J.M.]; European Molecular Biology Laboratory (EMBL) [core funds to M.J.M and M.M.]; Wellcome Trust [WT108749/Z/15/Z to M.M.]; S.K. is a royal Society University Research Fellow; Swiss ...