Dataset Information

Detection of alpha-rod protein repeats using a neural network and application to huntingtin.

ABSTRACT: A growing number of solved protein structures display an elongated structural domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel alpha-helices. Alpha-rods are flexible and expose a large surface, which makes them suitable for protein interaction. Although most likely originating by tandem duplication of a two-helix unit, their detection using sequence similarity between repeats is poor. Here, we show that alpha-rod repeats can be detected using a neural network. The network detects more repeats than are identified by domain databases using multiple profiles, with a low level of false positives (<10%). We identify alpha-rod repeats in approximately 0.4% of proteins in eukaryotic genomes. We then investigate the results for all human proteins, identifying alpha-rod repeats for the first time in six protein families, including proteins STAG1-3, SERAC1, and PSMD1-2 & 5. We also characterize a short version of these repeats in eight protein families of Archaeal, Bacterial, and Fungal species. Finally, we demonstrate the utility of these predictions in directing experimental work to demarcate three alpha-rods in huntingtin, a protein mutated in Huntington's disease. Using yeast two hybrid analysis and an immunoprecipitation technique, we show that the huntingtin fragments containing alpha-rods associate with each other. This is the first definition of domains in huntingtin and the first validation of predicted interactions between fragments of huntingtin, which sets up directions toward functional characterization of this protein. An implementation of the repeat detection algorithm is available as a Web server with a simple graphical output: http://www.ogic.ca/projects/ard. This can be further visualized using BiasViz, a graphic tool for representation of multiple sequence alignments.

SUBMITTER: Palidwor GA

PROVIDER: S-EPMC2647740 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Detection of alpha-rod protein repeats using a neural network and application to huntingtin.

Palidwor Gareth A GA Shcherbinin Sergey S Huska Matthew R MR Rasko Tamas T Stelzl Ulrich U Arumughan Anup A Foulle Raphaele R Porras Pablo P Sanchez-Pulido Luis L Wanker Erich E EE Andrade-Navarro Miguel A MA

PLoS computational biology 20090313 3

A growing number of solved protein structures display an elongated structural domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel alpha-helices. Alpha-rods are flexible and expose a large surface, which makes them suitable for protein interaction. Although most likely originating by tandem duplication of a two-helix unit, their detection using sequence similarity between repeats is poor. Here, we show that alpha-rod repeats can be detected using a neural network. The ne ...[more]

PMID: 19282972

Similar Datasets

Project description:Numerous brain disorders are associated with ventriculomegaly, including both neuro-degenerative diseases and cerebrospinal fluid disorders. Detailed evaluation of the ventricular system is important for these conditions to help understand the pathogenesis of ventricular enlargement and elucidate novel patterns of ventriculomegaly that can be associated with different diseases. One such disease is normal pressure hydrocephalus (NPH), a chronic form of hydrocephalus in older adults that causes dementia. Automatic parcellation of the ventricular system into its sub-compartments in patients with ventriculomegaly is quite challenging due to the large variation of the ventricle shape and size. Conventional brain labeling methods are time-consuming and often fail to identify the boundaries of the enlarged ventricles. We propose a modified 3D U-Net method to perform accurate ventricular parcellation, even with grossly enlarged ventricles, from magnetic resonance images (MRIs). We validated our method on a data set of healthy controls as well as a cohort of 95 patients with NPH with mild to severe ventriculomegaly and compared with several state-of-the-art segmentation methods. On the healthy data set, the proposed network achieved mean Dice similarity coefficient (DSC) of 0.895?±?0.03 for the ventricular system. On the NPH data set, we achieved mean DSC of 0.973?±?0.02, which is significantly (p?<?0.005) higher than four state-of-the-art segmentation methods we compared with. Furthermore, the typical processing time on CPU-base implementation of the proposed method is 2?min, which is much lower than the several hours required by the other methods. Results indicate that our method provides: 1) highly robust parcellation of the ventricular system that is comparable in accuracy to state-of-the-art methods on healthy controls; 2) greater robustness and significantly more accurate results on cases of ventricular enlargement; and 3) a tool that enables computation of novel imaging biomarkers for dilated ventricular spaces that characterize the ventricular system.

Dataset Information

Detection of alpha-rod protein repeats using a neural network and application to huntingtin.

Publications

Detection of alpha-rod protein repeats using a neural network and application to huntingtin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets