Dataset Information

Efficient and interpretable prediction of protein functional classes by correspondence analysis and compact set relations.

ABSTRACT: Predicting protein functional classes such as localization sites and modifications plays a crucial role in function annotation. Given a tremendous amount of sequence data yielded from high-throughput sequencing experiments, the need of efficient and interpretable prediction strategies has been rapidly amplified. Our previous approach for subcellular localization prediction, PSLDoc, archives high overall accuracy for Gram-negative bacteria. However, PSLDoc is computational intensive due to incorporation of homology extension in feature extraction and probabilistic latent semantic analysis in feature reduction. Besides, prediction results generated by support vector machines are accurate but generally difficult to interpret. In this work, we incorporate three new techniques to improve efficiency and interpretability. First, homology extension is performed against a compact non-redundant database using a fast search model to reduce running time. Second, correspondence analysis (CA) is incorporated as an efficient feature reduction to generate a clear visual separation of different protein classes. Finally, functional classes are predicted by a combination of accurate compact set (CS) relation and interpretable one-nearest neighbor (1-NN) algorithm. Besides localization data sets, we also apply a human protein kinase set to validate generality of our proposed method. Experiment results demonstrate that our method make accurate prediction in a more efficient and interpretable manner. First, homology extension using a fast search on a compact database can greatly accelerate traditional running time up to twenty-five times faster without sacrificing prediction performance. This suggests that computational costs of many other predictors that also incorporate homology information can be largely reduced. In addition, CA can not only efficiently identify discriminative features but also provide a clear visualization of different functional classes. Moreover, predictions based on CS achieve 100% precision. When combined with 1-NN on unpredicted targets by CS, our method attains slightly better or comparable performance compared with the state-of-the-art systems.

SUBMITTER: Chang JM

PROVIDER: S-EPMC3795737 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficient and interpretable prediction of protein functional classes by correspondence analysis and compact set relations.

Chang Jia-Ming JM Taly Jean-Francois JF Erb Ionas I Sung Ting-Yi TY Hsu Wen-Lian WL Tang Chuan Yi CY Notredame Cedric C Su Emily Chia-Yu EC

PloS one 20131011 10

Predicting protein functional classes such as localization sites and modifications plays a crucial role in function annotation. Given a tremendous amount of sequence data yielded from high-throughput sequencing experiments, the need of efficient and interpretable prediction strategies has been rapidly amplified. Our previous approach for subcellular localization prediction, PSLDoc, archives high overall accuracy for Gram-negative bacteria. However, PSLDoc is computational intensive due to incorp ...[more]

PMID: 24146760

Similar Datasets

Project description:Protein secondary structure prediction (SSP) has been an area of intense research interest. Despite advances in recent methods conducted on large datasets, the estimated upper limit accuracy is yet to be reached. Since the predictions of SSP methods are applied as input to higher-level structure prediction pipelines, even small errors may have large perturbations in final models. Previous works relied on cross validation as an estimate of classifier accuracy. However, training on large numbers of protein chains compromises the classifier ability to generalize to new sequences. This prompts a novel approach to training and an investigation into the possible structural factors that lead to poor predictions. Here, a small group of 55 proteins termed the compact model is selected from the CB513 dataset using a heuristics-based approach. In a prior work, all sequences were represented as probability matrices of residues adopting each of Helix, Sheet and Coil states, based on energy calculations using the C-Alpha, C-Beta, Side-chain (CABS) algorithm. The functional relationship between the conformational energies computed with CABS force-field and residue states is approximated using a classifier termed the Fully Complex-valued Relaxation Network (FCRN). The FCRN is trained with the compact model proteins.The performance of the compact model is compared with traditional cross-validated accuracies and blind-tested on a dataset of G Switch proteins, obtaining accuracies of ?81 %. The model demonstrates better results when compared to several techniques in the literature. A comparative case study of the worst performing chain identifies hydrogen bond contacts that lead to Coil ? Sheet misclassifications. Overall, mispredicted Coil residues have a higher propensity to participate in backbone hydrogen bonding than correctly predicted Coils.The implications of these findings are: (i) the choice of training proteins is important in preserving the generalization of a classifier to predict new sequences accurately and (ii) SSP techniques sensitive in distinguishing between backbone hydrogen bonding and side-chain or water-mediated hydrogen bonding might be needed in the reduction of Coil ? Sheet misclassifications.

Project description:BackgroundA cluster analysis is the most commonly performed procedure (often regarded as a first step) on a set of gene expression profiles. In most cases, a post hoc analysis is done to see if the genes in the same clusters can be functionally correlated. While past successes of such analyses have often been reported in a number of microarray studies (most of which used the standard hierarchical clustering, UPGMA, with one minus the Pearson's correlation coefficient as a measure of dissimilarity), often times such groupings could be misleading. More importantly, a systematic evaluation of the entire set of clusters produced by such unsupervised procedures is necessary since they also contain genes that are seemingly unrelated or may have more than one common function. Here we quantify the performance of a given unsupervised clustering algorithm applied to a given microarray study in terms of its ability to produce biologically meaningful clusters using a reference set of functional classes. Such a reference set may come from prior biological knowledge specific to a microarray study or may be formed using the growing databases of gene ontologies (GO) for the annotated genes of the relevant species.ResultsIn this paper, we introduce two performance measures for evaluating the results of a clustering algorithm in its ability to produce biologically meaningful clusters. The first measure is a biological homogeneity index (BHI). As the name suggests, it is a measure of how biologically homogeneous the clusters are. This can be used to quantify the performance of a given clustering algorithm such as UPGMA in grouping genes for a particular data set and also for comparing the performance of a number of competing clustering algorithms applied to the same data set. The second performance measure is called a biological stability index (BSI). For a given clustering algorithm and an expression data set, it measures the consistency of the clustering algorithm's ability to produce biologically meaningful clusters when applied repeatedly to similar data sets. A good clustering algorithm should have high BHI and moderate to high BSI. We evaluated the performance of ten well known clustering algorithms on two gene expression data sets and identified the optimal algorithm in each case. The first data set deals with SAGE profiles of differentially expressed tags between normal and ductal carcinoma in situ samples of breast cancer patients. The second data set contains the expression profiles over time of positively expressed genes (ORF's) during sporulation of budding yeast. Two separate choices of the functional classes were used for this data set and the results were compared for consistency.ConclusionFunctional information of annotated genes available from various GO databases mined using ontology tools can be used to systematically judge the results of an unsupervised clustering algorithm as applied to a gene expression data set in clustering genes. This information could be used to select the right algorithm from a class of clustering algorithms for the given data set.

Dataset Information

Efficient and interpretable prediction of protein functional classes by correspondence analysis and compact set relations.

Publications

Efficient and interpretable prediction of protein functional classes by correspondence analysis and compact set relations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets