Improving the Caenorhabditis elegans Genome Annotation Using Machine Learning

For modern biology, precise genome annotations are of prime importance, as they allow the accurate definition of genic regions. We employ state-of-the-art machine learning methods to assay and improve the accuracy of the genome annotation of the nematode Caenorhabditis elegans. The proposed machine learning system is trained to recognize exons and introns on the unspliced mRNA, utilizing recent advances in support vector machines and label sequence learning. In 87% (coding and untranslated regions) and 95% (coding regions only) of all genes tested in several out-of-sample evaluations, our method correctly identified all exons and introns. Notably, only 37% and 50%, respectively, of the presently unconfirmed genes in the C. elegans genome annotation agree with our predictions, thus we hypothesize that a sizable fraction of those genes are not correctly annotated. A retrospective evaluation of the Wormbase WS120 annotation [1] of C. elegans reveals that splice form predictions on unconfirmed genes in WS120 are inaccurate in about 18% of the considered cases, while our predictions deviate from the truth only in 10%–13%. We experimentally analyzed 20 controversial genes on which our system and the annotation disagree, confirming the superiority of our predictions. While our method correctly predicted 75% of those cases, the standard annotation was never completely correct. The accuracy of our system is further corroborated by a comparison with two other recently proposed systems that can be used for splice form prediction: SNAP and ExonHunter. We conclude that the genome annotation of C. elegans and other organisms can be greatly enhanced using modern machine learning technology

DNA Steganalysis Using Deep Recurrent Neural Networks

Recent advances in next-generation sequencing technologies have facilitated the use of deoxyribonucleic acid (DNA) as a novel covert channels in steganography. There are various methods that exist in other domains to detect hidden messages in conventional covert channels. However, they have not been applied to DNA steganography. The current most common detection approaches, namely frequency analysis-based methods, often overlook important signals when directly applied to DNA steganography because those methods depend on the distribution of the number of sequence characters. To address this limitation, we propose a general sequence learning-based DNA steganalysis framework. The proposed approach learns the intrinsic distribution of coding and non-coding sequences and detects hidden messages by exploiting distribution variations after hiding these messages. Using deep recurrent neural networks (RNNs), our framework identifies the distribution variations by using the classification score to predict whether a sequence is to be a coding or non-coding sequence. We compare our proposed method to various existing methods and biological sequence analysis methods implemented on top of our framework. According to our experimental results, our approach delivers a robust detection performance compared to other tools

On the Investigation of Biological Phenomena through Computational Intelligence

This paper is largely devoted for building a novel approach which is able to explain biological phenomena like splicing promoter gene identification disease and disorder identification and to acquire and exploit biological data This paper also presents an overview on the artificial neural network based computational intelligence technique to infer and analyze biological information from wide spectrum of complex problems Bioinformatics and computational intelligence are new research area which integrates many core subjects such as chemistry biology medical science mathematics computer and information science Since most of the problems in bioinformatics are inherently hard ill defined and possesses overlapping boundaries Neural networks have proved to be effective in solving those problems where conventional com-putation tools failed to provide solution Our experiments demonstrate the endeavor of biological phenomena as an effec-tive description for many intelligent applications Having a computational tool to predict genes and other meaningful in-formation is therefore of great value and can save a lot of expensive and time consuming experiments for biologists This paper will focus on issues related to design methodology comprising neural network to analyze biological information and investigate them for powerful application

Automatic intron detection in metagenomes using neural networks.

Tato práce se zabývá detekcí intronů v metagenomech hub pomocí hlubokých neuronových sítí. Přesné biologické mechanizmy rozpoznávání a vyřezávání intronů nejsou zatím plně známy a jejich strojová detekce není považovaná za vyřešený problém. Rozpoznávání a vyřezávání intronů z DNA sekvencí je důležité pro identifikaci genů v metagenomech a hledání jejich homologií mezi známými DNA sekvencemi,které jsou dostupné ve veřejných databázích. Rozpoznání genů a nalezení jejich případných homologů umožňuje identifikaci jak již známých tak i nových druhů a jejich taxonomické zařazení. V rámci práce vznikly dva modely neuronových sítí, které detekují začátky a konce intronů, takzvaná donorová a akceptorová místa sestřihu. Detekovaná místa sestřihu jsou následně zkombinována do kandidátních intronů. Překrývající se kandidátní introny jsou poté odstraněny pomocí jednoduchého skórovacího algoritmu. Práce navazuje na existující řešení, které využívá metody podpůrných vektorů (SVM). Výsledné neuronové sítě dosahují lepších výsledků než SVM a to při více než desetinásobně nižším výpočetním čase na zpracování stejně obsáhlého genomu.This work is concerned with the detection of introns in metagenomes with deep neural networks. Exact biological mechanisms of intron recognition and splicing are not fully known yet and their automated detection has remained unresolved. Detection and removal of introns from DNA sequences is important for the identification of genes in metagenomes and for searching for homologs among the known DNA sequences available in public databases. Gene prediction and the discovery of their homologs allows the identification of known and new species and their taxonomic classification. Two neural network models were developed as part of this thesis. The models' aim is the detection of intron starts and ends with the so-called donor and acceptor splice sites. The splice sites are later combined into candidate introns which are further filtered by a simple score-based overlap resolving algorithm. The work relates to an existing solution based on support vector machines (SVM). The resulting neural networks achieve better results than SVM and require more than order of magnitude less computational resources in order to process equally large genome

NOVEL APPLICATIONS OF MACHINE LEARNING IN BIOINFORMATICS

Technological advances in next-generation sequencing and biomedical imaging have led to a rapid increase in biomedical data dimension and acquisition rate, which is challenging the conventional data analysis strategies. Modern machine learning techniques promise to leverage large data sets for finding hidden patterns within them, and for making accurate predictions. This dissertation aims to design novel machine learning-based models to transform biomedical big data into valuable biological insights. The research presented in this dissertation focuses on three bioinformatics domains: splice junction classification, gene regulatory network reconstruction, and lesion detection in mammograms. A critical step in defining gene structures and mRNA transcript variants is to accurately identify splice junctions. In the first work, we built the first deep learning-based splice junction classifier, DeepSplice. It outperforms the state-of-the-art classification tools in terms of both classification accuracy and computational efficiency. To uncover transcription factors governing metabolic reprogramming in non-small-cell lung cancer patients, we developed TFmeta, a machine learning approach to reconstruct relationships between transcription factors and their target genes in the second work. Our approach achieves the best performance on benchmark data sets. In the third work, we designed deep learning-based architectures to perform lesion detection in both 2D and 3D whole mammogram images

Artificial intelligence used in genome analysis studies

Next Generation Sequencing (NGS) or deep sequencing technology enables parallel reading of multiple individual DNA fragments, thereby enabling the identification of millions of base pairs in several hours. Recent research has clearly shown that machine learning technologies can efficiently analyse large sets of genomic data and help to identify novel gene functions and regulation regions. A deep artificial neural network consists of a group of artificial neurons that mimic the properties of living neurons. These mathematical models, termed Artificial Neural Networks (ANN), can be used to solve artificial intelligence engineering problems in several different technological fields (e.g., biology, genomics, proteomics, and metabolomics). In practical terms, neural networks are non-linear statistical structures that are organized as modelling tools and are used to simulate complex genomic relationships between inputs and outputs. To date, Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNN) have been demonstrated to be the best tools for improving performance in problem solving tasks within the genomic field

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