Dataset Information

ASAP: a machine learning framework for local protein properties.

ABSTRACT: Determining residue-level protein properties, such as sites of post-translational modifications (PTMs), is vital to understanding protein function. Experimental methods are costly and time-consuming, while traditional rule-based computational methods fail to annotate sites lacking substantial similarity. Machine Learning (ML) methods are becoming fundamental in annotating unknown proteins and their heterogeneous properties. We present ASAP (Amino-acid Sequence Annotation Prediction), a universal ML framework for predicting residue-level properties. ASAP extracts numerous features from raw sequences, and supports easy integration of external features such as secondary structure, solvent accessibility, intrinsically disorder or PSSM profiles. Features are then used to train ML classifiers. ASAP can create new classifiers within minutes for a variety of tasks, including PTM prediction (e.g. cleavage sites by convertase, phosphoserine modification). We present a detailed case study for ASAP: CleavePred, an ASAP-based model to predict protein precursor cleavage sites, with state-of-the-art results. Protein cleavage is a PTM shared by a wide variety of proteins sharing minimal sequence similarity. Current rule-based methods suffer from high false positive rates, making them suboptimal. The high performance of CleavePred makes it suitable for analyzing new proteomes at a genomic scale. The tool is attractive to protein design, mass spectrometry search engines and the discovery of new bioactive peptides from precursors. ASAP functions as a baseline approach for residue-level protein sequence prediction. CleavePred is freely accessible as a web-based application. Both ASAP and CleavePred are open-source with a flexible Python API.Database URL: ASAP's and CleavePred source code, webtool and tutorials are available at: https://github.com/ddofer/asap; http://protonet.cs.huji.ac.il/cleavepred.

SUBMITTER: Brandes N

PROVIDER: S-EPMC5045867 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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ASAP: a machine learning framework for local protein properties.

Brandes Nadav N Ofer Dan D Linial Michal M

Database : the journal of biological databases and curation 20161002

Determining residue-level protein properties, such as sites of post-translational modifications (PTMs), is vital to understanding protein function. Experimental methods are costly and time-consuming, while traditional rule-based computational methods fail to annotate sites lacking substantial similarity. Machine Learning (ML) methods are becoming fundamental in annotating unknown proteins and their heterogeneous properties. We present ASAP (Amino-acid Sequence Annotation Prediction), a universal ...[more]

PMID: 27694209

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Project description:BACKGROUND:The selection and prioritization of drug targets is a central problem in drug discovery. Computational approaches can leverage the growing number of large-scale human genomics and proteomics data to make in-silico target identification, reducing the cost and the time needed. RESULTS:We developed a machine learning approach to score proteins to generate a druggability score of novel targets. In our model we incorporated 70 protein features which included properties derived from the sequence, features characterizing protein functions as well as network properties derived from the protein-protein interaction network. The advantage of this approach is that it is unbiased and even less studied proteins with limited information about their function can score well as most of the features are independent of the accumulated literature. We build models on a training set which consist of targets with approved drugs and a negative set of non-drug targets. The machine learning techniques help to identify the most important combination of features differentiating validated targets from non-targets. We validated our predictions on an independent set of clinical trial drug targets, achieving a high accuracy characterized by an Area Under the Curve (AUC) of 0.89. Our most predictive features included biological function of proteins, network centrality measures, protein essentiality, tissue specificity, localization and solvent accessibility. Our predictions, based on a small set of 102 validated oncology targets, recovered the majority of known drug targets and identifies a novel set of proteins as drug target candidates. CONCLUSIONS:We developed a machine learning approach to prioritize proteins according to their similarity to approved drug targets. We have shown that the method proposed is highly predictive on a validation dataset consisting of 277 targets of clinical trial drug confirming that our computational approach is an efficient and cost-effective tool for drug target discovery and prioritization. Our predictions were based on oncology targets and cancer relevant biological functions, resulting in significantly higher scores for targets of oncology clinical trial drugs compared to the scores of targets of trial drugs for other indications. Our approach can be used to make indication specific drug-target prediction by combining generic druggability features with indication specific biological functions.

Project description:BackgroundMoonlighting proteins (MPs) are a subclass of multifunctional proteins in which more than one independent or usually distinct function occurs in a single polypeptide chain. Identification of unknown cellular processes, understanding novel protein mechanisms, improving the prediction of protein functions, and gaining information about protein evolution are the main reasons to study MPs. They also play an important role in disease pathways and drug-target discovery. Since detecting MPs experimentally is quite a challenge, most of them are detected randomly. Therefore, introducing an appropriate computational approach to predict MPs seems reasonable.ResultsIn this study, we introduced a competent model for detecting moonlighting and non-MPs through extracted features from protein sequences. We attempted to set up a well-judged scheme for detecting outlier proteins. Consequently, 37 distinct feature vectors were utilized to study each protein's impact on detecting MPs. Furthermore, 8 different classification methods were assessed to find the best performance. To detect outliers, each one of the classifications was executed 100 times by tenfold cross-validation on feature vectors; proteins which misclassified 90 times or more were grouped. This process was applied to every single feature vector and eventually the intersection of these groups was determined as the outlier proteins. The results of tenfold cross-validation on a dataset of 351 samples (containing 215 moonlighting and 136 non-moonlighting proteins) reveal that the SVM method on all feature vectors has the highest performance among all methods in this study and other available methods. Besides, the study of outliers showed that 57 of 351 proteins in the dataset could be an appropriate candidate for the outlier. Among the outlier proteins, there were non-MPs (such as P69797) that have been misclassified in 8 different classification methods with 16 different feature vectors. Because these proteins have been obtained by computational methods, the results of this study could reduce the likelihood of hypothesizing whether these proteins are non-moonlighting at all.ConclusionsMPs are difficult to be identified through experimentation. Using distinct feature vectors, our method enabled identification of novel moonlighting proteins. The study also pinpointed that a number of non-MPs are likely to be moonlighting.

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ASAP: a machine learning framework for local protein properties.

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ASAP: a machine learning framework for local protein properties.

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