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Theses

Searching for novel peptide hormones in the human genome

Olivier Mirabeau 1
1 MAB - Méthodes et Algorithmes pour la Bioinformatique
LIRMM - Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier
Abstract : The goal of my thesis was to discover novel peptide hormones (PH) in the human genome. Peptide hormones (PH) are an important class of molecules that are involved in a broad range of normal and pathological physiological processes. PH are small secreted proteins that are processed from larger proteins, called precursors. In the first part of the thesis I introduce hidden Markov models (HMM)-based algorithms that allow for the modelling of those PH precursor sequences. This leads me to derive models of some of their well-known characteristic features, including signal peptides and prohormone convertase cleavage sites. Next, I make use of orthology information and modify the HMM algorithms so that the HMM can incorporate a conservation score that is calculated along protein sequence alignments. I show that this idea brings significant improvements in the quality of predictions and I conclude the chapter by drawing a list of potential candidate peptide hormones that was obtained by running the HMM algorithms on genome-wide protein sequence data. In the second and third part of the thesis I present data on the most interesting candidates that we named "spexin" and "augurin". I show in vitro subcellular localization, secretion and processing of those proteins after transfection of their coding DNA into endocrine cells. I then show mRNA and protein in vivo expression data in the mouse for those two proteins, and present functional data on spexin. I conclude both chapters by making some speculations on the functional significance of those two proteins. In the fourth part of the thesis I present data on the expression, secretion and processing of four extra candidate peptide hormones.
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Theses
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https://tel.archives-ouvertes.fr/tel-00340710
Contributor : Olivier Mirabeau <>
Submitted on : Friday, November 21, 2008 - 4:36:05 PM
Last modification on : Monday, October 19, 2020 - 11:06:42 AM
Long-term archiving on: : Thursday, October 11, 2012 - 11:56:00 AM

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  • HAL Id : tel-00340710, version 1

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Olivier Mirabeau. Searching for novel peptide hormones in the human genome. Life Sciences [q-bio]. Université Montpellier II - Sciences et Techniques du Languedoc, 2008. English. ⟨tel-00340710⟩

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