Daniel Navarro-Gomez1, Jeremy Leipzig1, Lishuang Shen1, Marie Lott1, Alphons P M Stassen1, Douglas C Wallace2, Janey L Wiggs1, Marni J Falk2, Mannis van Oven1, Xiaowu Gai1. 1. Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA, Center for Biomedical Informaticsand Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA, Department of Clinical Genetics, Maastricht University Medical Centre, The Netherlands, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA and Department of Forensic Molecular Biology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 2. Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA, Center for Biomedical Informaticsand Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA, Department of Clinical Genetics, Maastricht University Medical Centre, The Netherlands, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA and Department of Forensic Molecular Biology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA, Center for Biomedical Informaticsand Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA, Department of Clinical Genetics, Maastricht University Medical Centre, The Netherlands, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA and Department of Forensic Molecular Biology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract
MOTIVATION: All current mitochondrial haplogroup classification tools require variants to be detected from an alignment with the reference sequence and to be properly named according to the canonical nomenclature standards for describing mitochondrial variants, before they can be compared with the haplogroup determining polymorphisms. With the emergence of high-throughput sequencing technologies and hence greater availability of mitochondrial genome sequences, there is a strong need for an automated haplogroup classification tool that is alignment-free and agnostic to reference sequence. RESULTS: We have developed a novel mitochondrial genome haplogroup-defining algorithm using a k-mer approach namely Phy-Mer. Phy-Mer performs equally well as the leading haplogroup classifier, HaploGrep, while avoiding the errors that may occur when preparing variants to required formats and notations. We have further expanded Phy-Mer functionality such that next-generation sequencing data can be used directly as input. AVAILABILITY AND IMPLEMENTATION: Phy-Mer is publicly available under the GNU Affero General Public License v3.0 on GitHub (https://github.com/danielnavarrogomez/phy-mer). CONTACT: Xiaowu_Gai@meei.harvard.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
MOTIVATION: All current mitochondrial haplogroup classification tools require variants to be detected from an alignment with the reference sequence and to be properly named according to the canonical nomenclature standards for describing mitochondrial variants, before they can be compared with the haplogroup determining polymorphisms. With the emergence of high-throughput sequencing technologies and hence greater availability of mitochondrial genome sequences, there is a strong need for an automated haplogroup classification tool that is alignment-free and agnostic to reference sequence. RESULTS: We have developed a novel mitochondrial genome haplogroup-defining algorithm using a k-mer approach namely Phy-Mer. Phy-Mer performs equally well as the leading haplogroup classifier, HaploGrep, while avoiding the errors that may occur when preparing variants to required formats and notations. We have further expanded Phy-Mer functionality such that next-generation sequencing data can be used directly as input. AVAILABILITY AND IMPLEMENTATION: Phy-Mer is publicly available under the GNU Affero General Public License v3.0 on GitHub (https://github.com/danielnavarrogomez/phy-mer). CONTACT: Xiaowu_Gai@meei.harvard.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Authors: Doron M Behar; Mannis van Oven; Saharon Rosset; Mait Metspalu; Eva-Liis Loogväli; Nuno M Silva; Toomas Kivisild; Antonio Torroni; Richard Villems Journal: Am J Hum Genet Date: 2012-04-06 Impact factor: 11.025
Authors: Bruce Budowle; Deborah Polanskey; Constance L Fisher; Bobi K Den Hartog; Russell B Kepler; John W Elling Journal: J Forensic Sci Date: 2010-07-26 Impact factor: 1.832
Authors: S Anderson; A T Bankier; B G Barrell; M H de Bruijn; A R Coulson; J Drouin; I C Eperon; D P Nierlich; B A Roe; F Sanger; P H Schreier; A J Smith; R Staden; I G Young Journal: Nature Date: 1981-04-09 Impact factor: 49.962
Authors: Marni J Falk; Eric A Pierce; Mark Consugar; Michael H Xie; Moraima Guadalupe; Owen Hardy; Eric F Rappaport; Douglas C Wallace; Emily LeProust; Xiaowu Gai Journal: Discov Med Date: 2012-12 Impact factor: 2.970
Authors: Lishuang Shen; Marcella Attimonelli; Renkui Bai; Marie T Lott; Douglas C Wallace; Marni J Falk; Xiaowu Gai Journal: Hum Mutat Date: 2018-04-06 Impact factor: 4.878
Authors: Nina Marchi; Laura Winkelbach; Ilektra Schulz; Maxime Brami; Zuzana Hofmanová; Jens Blöcher; Carlos S Reyna-Blanco; Yoan Diekmann; Alexandre Thiéry; Adamandia Kapopoulou; Vivian Link; Valérie Piuz; Susanne Kreutzer; Sylwia M Figarska; Elissavet Ganiatsou; Albert Pukaj; Travis J Struck; Ryan N Gutenkunst; Necmi Karul; Fokke Gerritsen; Joachim Pechtl; Joris Peters; Andrea Zeeb-Lanz; Eva Lenneis; Maria Teschler-Nicola; Sevasti Triantaphyllou; Sofija Stefanović; Christina Papageorgopoulou; Daniel Wegmann; Joachim Burger; Laurent Excoffier Journal: Cell Date: 2022-05-12 Impact factor: 66.850
Authors: Petr Triska; Kristiyana Kaneva; Daria Merkurjev; Noor Sohail; Marni J Falk; Timothy J Triche; Jaclyn A Biegel; Xiaowu Gai Journal: Cancer Res Date: 2019-02-01 Impact factor: 12.701
Authors: Marni J Falk; Xiaowu Gai; Lishuang Shen; Maria Angela Diroma; Michael Gonzalez; Daniel Navarro-Gomez; Jeremy Leipzig; Marie T Lott; Mannis van Oven; Douglas C Wallace; Colleen Clarke Muraresku; Zarazuela Zolkipli-Cunningham; Patrick F Chinnery; Marcella Attimonelli; Stephan Zuchner Journal: Hum Mutat Date: 2016-03-21 Impact factor: 4.878
Authors: Elizabeth M McCormick; Marie T Lott; Matthew C Dulik; Lishuang Shen; Marcella Attimonelli; Ornella Vitale; Amel Karaa; Renkui Bai; Daniel E Pineda-Alvarez; Larry N Singh; Christine M Stanley; Stacey Wong; Anshu Bhardwaj; Daria Merkurjev; Rong Mao; Neal Sondheimer; Shiping Zhang; Vincent Procaccio; Douglas C Wallace; Xiaowu Gai; Marni J Falk Journal: Hum Mutat Date: 2020-11-10 Impact factor: 4.878
Authors: Daniel Fernandes; Kendra Sirak; Mario Novak; John A Finarelli; John Byrne; Edward Connolly; Jeanette E L Carlsson; Edmondo Ferretti; Ron Pinhasi; Jens Carlsson Journal: Sci Rep Date: 2017-01-30 Impact factor: 4.379
Authors: Kristiyana Kaneva; Katrina O'Halloran; Petr Triska; Xiyu Liu; Daria Merkurjev; Moiz Bootwalla; Alex Ryutov; Jennifer A Cotter; Dejerianne Ostrow; Jaclyn A Biegel; Xiaowu Gai Journal: Neurooncol Adv Date: 2021-06-02