Shallow learning model for diagnosing neuro muscular disorder from splicing variants
Authors: Kalimuthu Sathyavikasini , Vijayakumar Vijaya 
Published: June 2017

Purpose
Diagnosing genetic neuromuscular disorder such as muscular dystrophy is complicated when the imperfection occurs while splicing. This paper aims in predicting the type of muscular dystrophy from the gene sequences by extracting the well-defined descriptors related to splicing mutations. An automatic model is built to classify the disease through pattern recognition techniques coded in python using scikit-learn framework.

Design/methodology/approach
In this paper, the cloned gene sequences are synthesized based on the mutation position and its location on the chromosome by using the positional cloning approach. For instance, in the human gene mutational database (HGMD), the mutational information for splicing mutation is specified as IVS1-5 T > G indicates (IVS - intervening sequence or introns), first intron and five nucleotides before the consensus intron site AG, where the variant occurs in nucleotide G altered to T. IVS (+ve) denotes forward strand 3′– positive numbers from G of donor site invariant and IVS (−ve) denotes backward strand 5′ – negative numbers starting from G of acceptor site. The key idea in this paper is to spot out discriminative descriptors from diseased gene sequences based on splicing variants and to provide an effective machine learning solution for predicting the type of muscular dystrophy disease with the splicing mutations. Multi-class classification is worked out through data modeling of gene sequences. The synthetic mutational gene sequences are created, as the diseased gene sequences are not readily obtainable for this intricate disease. Positional cloning approach supports in generating disease gene sequences based on mutational information acquired from HGMD. SNP-, gene- and exon-based discriminative features are identified and used to train the model. An eminent muscular dystrophy disease prediction model is built using supervised learning techniques in scikit-learn environment. The data frame is built with the extracted features as numpy array. The data are normalized by transforming the feature values into the range between 0 and 1 aid in scaling the input attributes for a model. Naïve Bayes, decision tree, K-nearest neighbor and SVM learned models are developed using python library framework in scikit-learn.

Findings
To the best knowledge of authors, this is the foremost pattern recognition model, to classify muscular dystrophy disease pertaining to splicing mutations. Certain essential SNP-, gene- and exon-based descriptors related to splicing mutations are proposed and extracted from the cloned gene sequences. An eminent model is built using statistical learning technique through scikit-learn in the anaconda framework. This paper also deliberates the results of statistical learning carried out with the same set of gene sequences with synonymous and non-synonymous mutational descriptors.

Research limitations/implications
The data frame is built with the Numpy array. Normalizing the data by transforming the feature values into the range between 0 and 1 aid in scaling the input attributes for a model. Naïve Bayes, decision tree, K-nearest neighbor and SVM learned models are developed using python library framework in scikit-learn. While learning the SVM model, the cost, gamma and kernel parameters are tuned to attain good results. Scoring parameters of the classifiers are evaluated using tenfold cross-validation using metric functions of scikit-learn library. Results of the disease identification model based on non-synonymous, synonymous and splicing mutations were analyzed.

Practical implications
Certain essential SNP-, gene- and exon-based descriptors related to splicing mutations are proposed and extracted from the cloned gene sequences. An eminent model is built using statistical learning technique through scikit-learn in the anaconda framework. The performance of the classifiers are increased by using different estimators from the scikit-learn library. Several types of mutations such as missense, non-sense and silent mutations are also considered to build models through statistical learning technique and their results are analyzed.

Originality/value
To the best knowledge of authors, this is the foremost pattern recognition model, to classify muscular dystrophy disease pertaining to splicing mutations.