Evidence map›Paper›PMID 30453949›Full record

ArticleBMC medical genomics2018

Discovery and disentanglement of aligned residue associations from aligned pattern clusters to reveal subgroup characteristics.

Pei-Yuan Zhou, Antonio Sze-To, Andrew K C Wong

Abstract read
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Article in BMC medical genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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3citing papers in PubMed
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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Pei-Yuan ZhouSystems Design Engineering, University of Waterloo, Waterloo, ON, Canada.
Antonio Sze-ToSystems Design Engineering, University of Waterloo, Waterloo, ON, Canada.
Andrew K C WongSystems Design Engineering, University of Waterloo, Waterloo, ON, Canada. akcwong@uwaterloo.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA protein family has similar and diverse functions locally conserved. An aligned pattern cluster (APC) can reflect the conserved functionality. Discovering aligned residue associations (ARAs) in APCs can reveal subtle inner working characteristics of conserved regions of protein families. However, ARAs corresponding to different functionalities/subgroups/classes could be entangled because of subtle multiple entwined factors.

methodsTo discover and disentangle patterns from mixed-mode datasets, such as APCs when the residues are replaced by their fundamental biochemical properties list, this paper presents a novel method, Extended Aligned Residual Association Discovery and Disentanglement (E-ARADD). E-ARADD discretizes the numerical dataset to transform the mixed-mode dataset into an event-value dataset, constructs an ARA Frequency Matrix and then converts it into an adjusted Statistical Residual (SR) Vector Space (SRV) capturing statistical deviation from randomness. By applying Principal Component (PC) Decomposition on SRV, PCs ranked by their variance are obtained. Finally, the disentangled ARAs are discovered when the projections on a PC is re-projected to a vector space with the same basis vectors of SRV.

resultsExperiments on synthetic, cytochrome c and class A scavenger data have shown that E-ARADD can a) disentangle the entwined ARAs in APCs (with residues or biochemical properties), b) reveal subtle AR clusters relating to classes, subtle subgroups or specific functionalities.

conclusionsE-ARADD can discover and disentangle ARs and ARAs entangled in functionality and location of protein families to reveal functional subgroups and subgroup characteristics of biological conserved regions. Experimental results on synthetic data provides the proof-of-concept validation on the successful disentanglement that reveals class-associated ARAs with or without class labels as input. Experiments on cytochrome c data proved the efficacy of E-ARADD in handing both types of residue data. Our novel methodology is not only able to discover and disentangle ARs and ARAs in specific statistical/functional (PCs and RSRVs) spaces, but also their locations in the protein family functional domains. The success of E-ARADD shows its great potential to proteomic research, drug discovery and precision and personalized genetic medicine.

Indexed as

AlgorithmsCluster AnalysisComputational BiologyCytochromes cPrincipal Component AnalysisCytochromes cAligned pattern clustersAligned residue associationsDisentanglementPattern discoverySubgroup characteristics

Identifiers

PMID30453949
PMCPMC6245498

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.