TY - JOUR
T1 - Proteogenomic analysis of pathogenic yeast cryptococcus neoformans using high resolution mass spectrometry
AU - Selvan, Lakshmi Dhevi Nagarajha
AU - Kaviyil, Jyothi Embekkat
AU - Nirujogi, Raja Sekhar
AU - Muthusamy, Babylakshmi
AU - Puttamallesh, Vinuth N.
AU - Subbannayya, Tejaswini
AU - Syed, Nazia
AU - Radhakrishnan, Aneesha
AU - Kelkar, Dhanashree S.
AU - Ahmad, Sartaj
AU - Pinto, Sneha M.
AU - Kumar, Praveen
AU - Madugundu, Anil K.
AU - Nair, Bipin
AU - Chatterjee, Aditi
AU - Pandey, Akhilesh
AU - Ravikumar, Raju
AU - Gowda, Harsha
AU - Prasad, Thottethodi Subrahmanya Keshava
N1 - Funding Information:
We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics. The study was supported by a research grant “DBT Programme Support on Neuroproteomics of Neurological Disorders” to IOB and NIMHANS by DBT, Government of India (BT/01/COE/08/05). Jyothi Embekkat Kaviyil is a recipient of Senior Research Fellowship from Indian Council for Medical Research (ICMR), Government of India. Raja Sekhar Nirujogi, Babylakshmi Muthusamy, Aneesha Radhakrishnan and Sneha M. Pinto are recipients of Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. Nazia Syed, Sartaj Ahmad and Dhanashree S. Kelkar are recipients of Senior Research Fellowship from the University Grants Commission (UGC), Government of India. Anil K. Madugundu is the recipient of BINC-Junior Research Fellowship from DBT, India. Harsha Gowda is a Wellcome Trust/DBT India Alliance Early Career Fellow. T. S. Keshava Prasad is supported by a research grant on “Development of Infrastructure and a Computational Framework for Analysis of Proteomic Data” from DBT. We thank Agilent Technologies for instrumentation support.
PY - 2014
Y1 - 2014
N2 - Background: Cryptococcus neoformans, a basidiomycetous fungus of universal occurrence, is a significant opportunistic human pathogen causing meningitis. Owing to an increase in the number of immunosuppressed individuals along with emergence of drug-resistant strains, C. neoformans is gaining importance as a pathogen. Although, whole genome sequencing of three varieties of C. neoformans has been completed recently, no global proteomic studies have yet been reported. Results: We performed a comprehensive proteomic analysis of C. neoformans var. grubii (Serotype A), which is the most virulent variety, in order to provide protein-level evidence for computationally predicted gene models and to refine the existing annotations. We confirmed the protein-coding potential of 3,674 genes from a total of 6,980 predicted protein-coding genes. We also identified 4 novel genes and corrected 104 predicted gene models. In addition, our studies led to the correction of translational start site, splice junctions and reading frame used for translation in a number of proteins. Finally, we validated a subset of our novel findings by RT-PCR and sequencing. Conclusions: Proteogenomic investigation described here facilitated the validation and refinement of computationally derived gene models in the intron-rich genome of C. neoformans, an important fungal pathogen in humans.
AB - Background: Cryptococcus neoformans, a basidiomycetous fungus of universal occurrence, is a significant opportunistic human pathogen causing meningitis. Owing to an increase in the number of immunosuppressed individuals along with emergence of drug-resistant strains, C. neoformans is gaining importance as a pathogen. Although, whole genome sequencing of three varieties of C. neoformans has been completed recently, no global proteomic studies have yet been reported. Results: We performed a comprehensive proteomic analysis of C. neoformans var. grubii (Serotype A), which is the most virulent variety, in order to provide protein-level evidence for computationally predicted gene models and to refine the existing annotations. We confirmed the protein-coding potential of 3,674 genes from a total of 6,980 predicted protein-coding genes. We also identified 4 novel genes and corrected 104 predicted gene models. In addition, our studies led to the correction of translational start site, splice junctions and reading frame used for translation in a number of proteins. Finally, we validated a subset of our novel findings by RT-PCR and sequencing. Conclusions: Proteogenomic investigation described here facilitated the validation and refinement of computationally derived gene models in the intron-rich genome of C. neoformans, an important fungal pathogen in humans.
KW - Antifungal drugs
KW - Computational prediction
KW - Cryptococcal meningitis
KW - Fungal genomics
KW - Fungal infection
KW - Genome annotation
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U2 - 10.1186/1559-0275-11-5
DO - 10.1186/1559-0275-11-5
M3 - Article
AN - SCOPUS:84903795994
SN - 1542-6416
VL - 11
JO - Clinical Proteomics
JF - Clinical Proteomics
IS - 1
M1 - 5
ER -