title: Neglected tropical diseases and omics science: proteogenomics analysis of the promastigote stage of Leishmania major parasite.
abstract: Among the neglected tropical diseases, leishmaniasis is one of the most devastating, resulting in significant mortality and contributing to nearly 2 million disability-adjusted life years. Cutaneous leishmaniasis is a debilitating disorder caused by the kinetoplastid protozoan parasite Leishmania major, which results in disfiguration and scars. L. major genome was the first to be sequenced within the genus Leishmania. Use of proteomic data for annotating genomes is a complementary approach to conventional genome annotation approaches and is referred to as proteogenomics. We have used a proteogenomics-based approach to map the proteome of L. major and also annotate its genome. In this study, we searched L. major promastigote proteomic data against the annotated L. major protein database. Additionally, we searched the proteomic data against six-frame translated L. major genome. In all, we identified 3613 proteins in L. major promastigotes, which covered 43% of its proteome. We also identified 26 genome search-specific peptides, which led to the identification of three novel genes previously not identified in L. major. We also corrected the annotation of N-termini of 15 genes, which resulted in extension of their protein products. We have validated our proteogenomics findings by RT-PCR and sequencing. In addition, our study resulted in identification of 266 N-terminally acetylated peptides in L. major, one of the largest acetylated peptide datasets thus far in Leishmania. This dataset should be a valuable resource to researchers focusing on neglected tropical diseases.
authors.affiliation: 1 Institute of Bioinformatics , International Technology Park, Bangalore, India .
authors.forename: Harsh
authors.initials: H
authors.lastname: Pawar
authors.forename: Santosh
authors.initials: S
authors.lastname: Renuse
authors.forename: Sweta N
authors.initials: SN
authors.lastname: Khobragade
authors.forename: Sandip
authors.initials: S
authors.lastname: Chavan
authors.forename: Gajanan
authors.initials: G
authors.lastname: Sathe
authors.forename: Praveen
authors.initials: P
authors.lastname: Kumar
authors.forename: Kiran N
authors.initials: KN
authors.lastname: Mahale
authors.forename: Kalpita
authors.initials: K
authors.lastname: Gore
authors.forename: Aditi
authors.initials: A
authors.lastname: Kulkarni
authors.forename: Tanwi
authors.initials: T
authors.lastname: Dixit
authors.forename: Rajesh
authors.initials: R
authors.lastname: Raju
authors.forename: T S Keshava
authors.initials: TS
authors.lastname: Prasad
authors.forename: H C
authors.initials: HC
authors.lastname: Harsha
authors.forename: Milind S
authors.initials: MS
authors.lastname: Patole
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
mesh_terms: D000595:Amino Acid Sequence; D002478:Cells, Cultured; D063990:Gene Ontology; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018320:Leishmania major / Q000235:genetics / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D058069:Neglected Diseases / Q000469:parasitology; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry
chemical_list: D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D020543:Proteome; D015800:Protozoan Proteins