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

Seven clusters in genomic triplet distributions

Motivation: In several recent papers new algorithms were proposed for detecting coding regions without requiring learning dataset of already known genes. In this paper we studied cluster structure of several genomes in the space of codon usage. This allowed to interpret some of the results obtained in other studies and propose a simpler method, which is, nevertheless, fully functional. Results: Several complete genomic sequences were analyzed, using visualization of tables of triplet counts in a sliding window. The distribution of 64-dimensional vectors of triplet frequencies displays a well-detectable cluster structure. The structure was found to consist of seven clusters, corresponding to protein-coding information in three possible phases in one of the two complementary strands and in the non-coding regions. Awareness of the existence of this structure allows development of methods for the segmentation of sequences into regions with the same coding phase and non-coding regions. This method may be completely unsupervised or use some external information. Since the method does not need extraction of ORFs, it can be applied even for unassembled genomes. Accuracy calculated on the base-pair level (both sensitivity and specificity) exceeds 90%. This is not worse as compared to such methods as HMM, however, has the advantage to be much simpler and clear

PLIT: An alignment-free computational tool for identification of long non-coding RNAs in plant transcriptomic datasets

Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs which play a significant role in several biological processes. RNA-seq based transcriptome sequencing has been extensively used for identification of lncRNAs. However, accurate identification of lncRNAs in RNA-seq datasets is crucial for exploring their characteristic functions in the genome as most coding potential computation (CPC) tools fail to accurately identify them in transcriptomic data. Well-known CPC tools such as CPC2, lncScore, CPAT are primarily designed for prediction of lncRNAs based on the GENCODE, NONCODE and CANTATAdb databases. The prediction accuracy of these tools often drops when tested on transcriptomic datasets. This leads to higher false positive results and inaccuracy in the function annotation process. In this study, we present a novel tool, PLIT, for the identification of lncRNAs in plants RNA-seq datasets. PLIT implements a feature selection method based on L1 regularization and iterative Random Forests (iRF) classification for selection of optimal features. Based on sequence and codon-bias features, it classifies the RNA-seq derived FASTA sequences into coding or long non-coding transcripts. Using L1 regularization, 31 optimal features were obtained based on lncRNA and protein-coding transcripts from 8 plant species. The performance of the tool was evaluated on 7 plant RNA-seq datasets using 10-fold cross-validation. The analysis exhibited superior accuracy when evaluated against currently available state-of-the-art CPC tools

Neural Network and Bioinformatic Methods for Predicting HIV-1 Protease Inhibitor Resistance

This article presents a new method for predicting viral resistance to seven protease inhibitors from the HIV-1 genotype, and for identifying the positions in the protease gene at which the specific nature of the mutation affects resistance. The neural network Analog ARTMAP predicts protease inhibitor resistance from viral genotypes. A feature selection method detects genetic positions that contribute to resistance both alone and through interactions with other positions. This method has identified positions 35, 37, 62, and 77, where traditional feature selection methods have not detected a contribution to resistance. At several positions in the protease gene, mutations confer differing degress of resistance, depending on the specific amino acid to which the sequence has mutated. To find these positions, an Amino Acid Space is introduced to represent genes in a vector space that captures the functional similarity between amino acid pairs. Feature selection identifies several new positions, including 36, 37, and 43, with amino acid-specific contributions to resistance. Analog ARTMAP networks applied to inputs that represent specific amino acids at these positions perform better than networks that use only mutation locations.Air Force Office of Scientific Research (F49620-01-1-0423); National Geospatial-Intelligence Agency (NMA 201-01-1-2016); National Science Foundation (SBE-0354378); Office of Naval Research (N00014-01-1-0624

On Critical Relative Distance of DNA Codes for Additive Stem Similarity

We consider DNA codes based on the nearest-neighbor (stem) similarity model which adequately reflects the "hybridization potential" of two DNA sequences. Our aim is to present a survey of bounds on the rate of DNA codes with respect to a thermodynamically motivated similarity measure called an additive stem similarity. These results yield a method to analyze and compare known samples of the nearest neighbor "thermodynamic weights" associated to stacked pairs that occurred in DNA secondary structures.Comment: 5 or 6 pages (compiler-dependable), 0 figures, submitted to 2010 IEEE International Symposium on Information Theory (ISIT 2010), uses IEEEtran.cl

Use of Average Mutual Information and Derived Measures to Find Coding Regions

One of the important steps in the annotation of genomes is the identification of regions in the genome which code for proteins. One of the tools used by most annotation approaches is the use of signals extracted from genomic regions that can be used to identify whether the region is a protein coding region. Motivated by the fact that these regions are information bearing structures we propose signals based on measures motivated by the average mutual information for use in this task. We show that these signals can be used to identify coding and noncoding sequences with high accuracy. We also show that these signals are robust across species, phyla, and kingdom and can, therefore, be used in species agnostic genome annotation algorithms for identifying protein coding regions. These in turn could be used for gene identification

Using signal processing, evolutionary computation, and machine learning to identify transposable elements in genomes

About half of the human genome consists of transposable elements (TE's), sequences that have many copies of themselves distributed throughout the genome. All genomes, from bacterial to human, contain TE's. TE's affect genome function by either creating proteins directly or affecting genome regulation. They serve as molecular fossils, giving clues to the evolutionary history of the organism. TE's are often challenging to identify because they are fragmentary or heavily mutated. In this thesis, novel features for the detection and study of TE's are developed. These features are of two types. The first type are statistical features based on the Fourier transform used to assess reading frame use. These features measure how different the reading frame use is from that of a random sequence, which reading frames the sequence is using, and the proportion of use of the active reading frames. The second type of feature, called side effect machine (SEM) features, are generated by finite state machines augmented with counters that track the number of times the state is visited. These counters then become features of the sequence. The number of possible SEM features is super-exponential in the number of states. New methods for selecting useful feature subsets that incorporate a genetic algorithm and a novel clustering method are introduced. The features produced reveal structural characteristics of the sequences of potential interest to biologists. A detailed analysis of the genetic algorithm, its fitness functions, and its fitness landscapes is performed. The features are used, together with features used in existing exon finding algorithms, to build classifiers that distinguish TE's from other genomic sequences in humans, fruit flies, and ciliates. The classifiers achieve high accuracy (> 85%) on a variety of TE classification problems. The classifiers are used to scan large genomes for TE's. In addition, the features are used to describe the TE's in the newly sequenced ciliate, Tetrahymena thermophile to provide information for biologists useful to them in forming hypotheses to test experimentally concerning the role of these TE's and the mechanisms that govern them