EU H2020 Project "TTNPRED (Development of novel computational biology pipeline for the efficient..)": description, partecipants, costs and EC-fundings

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TTNPred project word cloud

Explore the words cloud of the TTNPred project. It provides you a very rough idea of what is the project "TTNPred" about.

bioinformatics pertinent molecular methodology mutations pathogenic community accumulating mechanistic vulnerability routine disorders msnp scoring 17 centric first detecting extrapolated domain heart functional truncations spots predictions clinicians filtering msnps calculations patients data components loci pipeline human staggering protein effect disease repetition distributed titin substantial medium screening feasible benchmarked training poly function populations experimentally aid risk single diagnostic cohorts free energy calculated estimating databases truncation poorly biophysical harvest considering predicts patient link conformational existent gt dna models clinically hot evaluation stable intervention muscle exchange stages rest ultimately clarified tool map polymorphisms throughput genomics subsequent nucleotide 75 classification biochemical chain giant predictors structural missense dynamics

Project "TTNPred" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITAT KONSTANZ Organization address address: UNIVERSITATSSTRASSE 10 city: KONSTANZ postcode: 78464 website: www.uni-konstanz.de/ contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Germany [DE]
Total cost	171˙460 €
EC max contribution	171˙460 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2016
Funding Scheme	MSCA-IF-EF-ST
Starting year	2018
Duration (year-month-day)	from 2018-01-01 to 2020-02-28

#	participants	country	role	EC contrib. [€]
1	UNIVERSITAT KONSTANZ	DE (KONSTANZ)	coordinator	171˙460.00

UNIVERSITAT KONSTANZ

DE (KONSTANZ)

coordinator

171˙460.00

Project objective

Mutations in the giant muscle protein titin are a major cause of heart disorders in human populations. Routine DNA screening of patient cohorts is now becoming feasible, with a staggering number of titin truncations and missense single nucleotide polymorphisms (mSNPs) rapidly accumulating in genomics databases (>17,000 mSNPs). While the link between titin truncation and disease is now becoming clarified, detecting the pathogenic potential of mSNPs remains a substantial challenge. In mSNPs classification, bioinformatics evaluation is a necessary first filtering step, but existing predictors are poorly reliable. To address this problem, we aim to develop a new titin-centric scoring function that predicts the mechanistic effect of an mSNP exchange in the titin protein by considering the specific characteristics of its poly-domain chain. For this work, we will build a medium-throughput molecular diagnostic pipeline that harvest existent structural models of titin components in estimating mSNPs-induced changes in free energy and conformational dynamics in the protein. Calculations will be benchmarked against experimentally obtained biophysical and biochemical data. To develop this methodology, we will use a clinically pertinent training set of 75 mSNPs. However, in a subsequent step, stable predictions will be extrapolated to the rest of the titin chain by exploiting the repetition of structural and functional loci within the chain. A titin map of vulnerability “hot-spots” so calculated will be distributed to the research community. Ultimately, we aim to produce a tool that can aid clinicians to identify patients at risk of developing a titin-based heart condition at early disease stages, where intervention is still possible.

Publications

List of publications.
year	authors and title	journal	last update
2019	Yevheniia Nesterenko, Christopher J. Hill, Jennifer R. Fleming, Patricia Murray, Olga Mayans The ZT Biopolymer: A Self-Assembling Protein Scaffold for Stem Cell Applications published pages: 4299, ISSN: 1422-0067, DOI: 10.3390/ijms20174299	International Journal of Molecular Sciences 20/17	2019-09-09
2019	Christopher J. Hill, Jennifer R. Fleming, Masoumeh Mousavinejad, Rachael Nicholson, Svetomir B. Tzokov, Per A. Bullough, Julius Bogomolovas, Mark R. Morgan, Olga Mayans, Patricia Murray Self-Assembling Proteins as High-Performance Substrates for Embryonic Stem Cell Self-Renewal published pages: 1807521, ISSN: 0935-9648, DOI: 10.1002/adma.201807521	Advanced Materials	2019-06-03
2019	Michael Adams, Jennifer R. Fleming, Eva Riehle, Tiankun Zhou, Thomas Zacharchenko, Marija Markovic, Olga Mayans Scalable, Non-denaturing Purification of Phosphoproteins Using Ga3+-IMAC: N2A and M1M2 Titin Components as Study case published pages: 181-189, ISSN: 1572-3887, DOI: 10.1007/s10930-019-09815-w	The Protein Journal 38/2	2019-09-05

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