Dataset Information

Neuroproteomics with Systems Biology: The proteomic landscape of adult human hypothalamus

ABSTRACT: The hypothalamus is an anatomically small, but functionally crucial region of the human brain. Normal hypothalamus functioning is central to the regulation of neuroendocrine and neurovegetative systems as well as modulation of chronobiology and behavioral aspects of the human body. Till date the human hypothalamus proteome profile is lacking from literature. In this study, we attempt to delineate the human hypothalamus proteome using high-resolution mass spectrometry approach. We identified a total of 5,349 proteins in the proteomics study. The unassigned spectra from the proteomics study were further used for identifying multiple post translational modification sites as well as for proteogenomics analysis. This resulted in the identification of 616 additional proteins. We observed a higher representation of mitochondrial and synaptic proteins in the proteomics data, as well as enrichment of pathways supporting the hypothalamic involvement in autophagy and adult neurogenesis. Interestingly, the phospholipase D signaling pathway emerged as a junction to the various aspects of hypothalamic functions, and relation to neurodegenerative disorders. Additionally, the investigation for multiple post translational modifications led to the identification of several known and novel post translational modification sites. A total of 13,544 peptides corresponding to 2,542 proteins with modifications of R/K-methylation, S/T/Y-phosphorylation, N/Q-deamidation, R-citrullination, and K-acetylation have been reported in this study. Proteogenomic analysis of hypothalamus resulted in the identification of 291 GSSPs which were further categorised into probable gene correction events. Among these, we confirmed 28 peptides to confer evidence for 10 predicted pseudogenes with coding potential, 4 novel protein-coding (3 novel isoforms, and 1 novel SEP), and 3 protein correction (1 novel exon, 1 alternate frame of translation and 1 N-terminal protein extension) events. We believe that hypothalamic proteome would aid as a platform to decipher the molecular basis for the diverse range of functions performed by this region and provide a baseline for exploring the role of these proteins in neurological health and disorders.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Keshava Prasad T. S.

LAB HEAD: Thottethodi Subrahmanya Keshava Prasad

PROVIDER: PXD026879 | Pride | 2021-11-01

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Hypothal_PTMwithMSF_070619.msf	Msf
	Hypothal_PTMwithMSF_070619.pdResult	Other
	Hypothalamus_10_HBP.raw	Raw
	Hypothalamus_1_HBP.raw	Raw
	Hypothalamus_2_HBP.raw	Raw

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Publications

The Normal Human Adult Hypothalamus Proteomic Landscape: Rise of Neuroproteomics in Biological Psychiatry and Systems Biology.

Chatterjee Oishi O Gopalakrishnan Lathika L Mol Praseeda P Advani Jayshree J Nair Bipin B Shankar Susarla Krishna SK Mahadevan Anita A Prasad Thottethodi Subrahmanya Keshava TSK

Omics : a journal of integrative biology 20211029 11

The human hypothalamus is central to the regulation of neuroendocrine and neurovegetative systems, as well as modulation of chronobiology and behavioral aspects in human health and disease. Surprisingly, a deep proteomic analysis of the normal human hypothalamic proteome has been missing for such an important organ so far. In this study, we delineated the human hypothalamus proteome using a high-resolution mass spectrometry approach which resulted in the identification of 5349 proteins, while a ...[more]

PMID: 34714154

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