Rerepresenting and Restructuring Domain Theories: A Constructive Induction Approach

Theory revision integrates inductive learning and background knowledge by combining training examples with a coarse domain theory to produce a more accurate theory. There are two challenges that theory revision and other theory-guided systems face. First, a representation language appropriate for the initial theory may be inappropriate for an improved theory. While the original representation may concisely express the initial theory, a more accurate theory forced to use that same representation may be bulky, cumbersome, and difficult to reach. Second, a theory structure suitable for a coarse domain theory may be insufficient for a fine-tuned theory. Systems that produce only small, local changes to a theory have limited value for accomplishing complex structural alterations that may be required. Consequently, advanced theory-guided learning systems require flexible representation and flexible structure. An analysis of various theory revision systems and theory-guided learning systems reveals specific strengths and weaknesses in terms of these two desired properties. Designed to capture the underlying qualities of each system, a new system uses theory-guided constructive induction. Experiments in three domains show improvement over previous theory-guided systems. This leads to a study of the behavior, limitations, and potential of theory-guided constructive induction.Comment: See http://www.jair.org/ for an online appendix and other files accompanying this articl

Discerning Novel Splice Junctions Derived from RNA-Seq Alignment: A Deep Learning Approach

Background: Exon splicing is a regulated cellular process in the transcription of protein-coding genes. Technological advancements and cost reductions in RNA sequencing have made quantitative and qualitative assessments of the transcriptome both possible and widely available. RNA-seq provides unprecedented resolution to identify gene structures and resolve the diversity of splicing variants. However, currently available ab initio aligners are vulnerable to spurious alignments due to random sequence matches and sample-reference genome discordance. As a consequence, a significant set of false positive exon junction predictions would be introduced, which will further confuse downstream analyses of splice variant discovery and abundance estimation. Results: In this work, we present a deep learning based splice junction sequence classifier, named DeepSplice, which employs convolutional neural networks to classify candidate splice junctions. We show (I) DeepSplice outperforms state-of-the-art methods for splice site classification when applied to the popular benchmark dataset HS3D, (II) DeepSplice shows high accuracy for splice junction classification with GENCODE annotation, and (III) the application of DeepSplice to classify putative splice junctions generated by Rail-RNA alignment of 21,504 human RNA-seq data significantly reduces 43 million candidates into around 3 million highly confident novel splice junctions. Conclusions: A model inferred from the sequences of annotated exon junctions that can then classify splice junctions derived from primary RNA-seq data has been implemented. The performance of the model was evaluated and compared through comprehensive benchmarking and testing, indicating a reliable performance and gross usability for classifying novel splice junctions derived from RNA-seq alignment

Prediction of Alternative Splice Sites in Human Genes

This thesis addresses the problem of predicting alternative splice sites in human genes. The most common way to identify alternative splice sites are the use of expressed sequence tags and microarray data. Since genes only produce alternative proteins under certain conditions, these methods are limited to detecting only alternative splice sites in genes whose alternative protein forms are expressed under the tested conditions. I have introduced three multiclass support vector machines that predict upstream and downstream alternative 3’ splice sites, upstream and downstream alternative 5’ splice sites, and the 3’ splice site of skipped and cryptic exons. On a test set extracted from the Alternative Splice Annotation Project database, I was able to correctly classify about 68% of the splice sites in the alternative 3’ set, about 62% of the splice sites in the alternative 5’ set, and about 66% in the exon skipping set