DNA/Gene Classification Using RNN Sequential Analysis

Abstract

Each active life has complex molecules in their cells called DNA (Deoxyribonucleic Acid) which are responsible for all biological features. These DNA molecules are further reduced into grander structures called chromosomes, which together compose the being’s genome. Genes are size altering DNA sequences which comprise code that are frequently used to produce proteins.

There has been a struggle to reliably try to identify the gene sequences since the entire anthropological genome has been sequenced. Gene classification and prediction are difficult tasks to be executed, by numerous variables conditioning its efficiency. Developments in machine learning concepts has enhanced the prediction and classification of DNA sequences.

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Deep Learning (DL) can be observed as a progress of the Artificial Neural Networks technology, are proficient to abstract significant features from raw data, and to practice these features for classification tasks. This report presents deep learning neural network for DNA sequence classification based on spectral sequence depiction. In case of datasets having huge number of attributes DL is relatively suitable to manage classification/regression tasks. This report points towards the learning of prediction and classification of genomic sequences and further improves knowledge in the field of gene classification using a DL model named RNN,

The deep recurrent neural network (RNN) designs can be used to trap the structure in a genetic sequence. By relating the perplexity attained after training on actual genome to that attained after training on a random sequence of nucleotides, we can confirm that a character level RNN can seize the non-random parts of DNA

Introduction

In recent years, deep RNNs are used by researchers to manage numerous machine learning difficulties in the province of NLP. Most of these applications examine complications like named entity recognition, translation and sentiment analysis. A smaller amount of work has been completed with RNNs on what is possibly the most natural language: the genome, a sequence of 4 letters (A, C, G, T). The persistence of this report is to discover how an RNN architecture can be used to study sequential patterns in genomic sequences. To confirm that an RNN can model the structure in a genomic sequence, firstly we train a simple character-level RNN to predict one of the 4 likely characters assumed the prior string of characters.

In case the capability of an RNN to forecast the subsequent character for a real genome is as similar as for a random genome, then we need to more cautiously tweak our model till we recognize some signal. This simple task is used to assist in selecting an appropriate model architecture. As soon as we have empirical evidence that an RNN could seize the non-random structure in a genome, we discover a sequence classification problem. Biological researches have revealed that subsequences of the anthropological genome are frequently controlled equally by neighboring and very distant sequences. Biologists have been able to recognize whether a specific genomic feature will be detected for a specific sequence. Few examples of these features comprise

• a. DNase I hypersensitive sites: sequences that are delicate to cleavage by the DNase I enzyme
• b. Histone marks: chemical changes to histone proteins, biomolecules which control certain sequences.
• c. Transcription factors: proteins that bind to a specific sequence

Overview of RNN

RNN is a class of artificial neural network where networks amongst units form a directed graph along a sequence. This permits it to display progressive behavior for a time sequence. RNNs use their internal memory to process sequences of inputs. This makes them appropriate to tasks like unsegmented and speech recognition.

Recurrent Neural Networks (RNN) were formed to report the faults in ANN that didn’t make conclusions based on prior knowledge. A characteristic ANN had learned to make conclusions depending on situation in training, but once it was building conclusions for use, the conclusions were made autonomous of each other.

Recurrent Neural Network arises into the depiction when any model requires context to be able to deliver the output based on the input provided.

Literature Review

Sequences in biology certainly fit the processing power of RNNs. This is due to the temporal modeling abilities of RNNs. By using iterative function loops, they stock information from input sequences. As they stock framework information in a flexible way, RNNs are a perfect architecture for sequence labelling tasks. They take input data in different forms and illustrations, by having the knowledge of what to stock and what to ignore. Also, they can comprehend sequential patterns in the existence of sequential noise (Graves, 2012). The time window method used by additional nonsequential networks suffers from shortage of robustness counter to sequential misrepresentations and the necessity to manually regulate the window length. It also surges the quantity of weights in the network. The other alternative method is to announce a delay from input processing to output generation. This method is robust in contrast to sequential misrepresentations but the delay sequence should be manually determined. Also, the network should recollect original inputs during the delay (Graves, 2012). A suitable approach to better comprehend RNN architectures is to unfold the cyclical connections through a graph, where each time step forms a node and shares the similar weights as other nodes (Graves, 2012).

Certainly, RNNs are powerful architectures. As RNN-Turing machines can also implement this kind of functions, the author demonstrates their equivalence by relating an RNN based on perceptron’s with a program executing a computable function. This similarity is found in terms of the transitions of states to the program flow and the network internal state to the program state.

Problem Statement

Gene classification using RNN is the problem of categorizing the functionality of genes using only the sequence data (ATGTGT….) repeatedly. This problem can be solved using RNN which will monitor the sequence and deliver meaningful data. They can integrate contextual data from past inputs, with the benefit to be robust to constrained distortions of the input sequence along the time. In this research RNN based network is used for the DNA/gene classification. RNN is a kind of recurrent neural networks with a more composite computational unit that leads to improved performance. RNN model in this research is developed using tensorflow python package. RNNs are mostly used for handing out sequences of data which progresses along the time axis. Sequences do not have explicit features, and the usually used illustrations announce the disadvantage of the high dimensionality. For sure, machine learning techniques dedicated to supervised classification tasks are dependent on the feature extraction stage, and to shape a good illustration it is required to identify and measure meaningful particulars of the items. The multi-task learning notion disturbs the models, both in terms of required training time and performance.

Methodology

• a. Collection of Data and Preparation of Dataset: Genomic sequences in the dataset is from 16S dataset. Pictures in the dataset were clustered into 5 dissimilar classes.
• b. Character Embedding: It is done by character level one hot encoding. This illustration considers each character ‘i’ of the alphabet through a vector of length equivalent to the size of the alphabet, having all zero entries excluding a single one in location ‘i’. This method also leads to a sparse illustration of the input provided, which is undertaken in the NLP literature through an embedding layer.
• c. Training: Training the deep convolution neural network for making an image classification model is done. CaffeNet architecture is used and attuned to support our 15 classes. Rectified Linear Units also known as ReLU are used as the substitution for saturating nonlinearities. This activation function adaptively studies the parameters of rectifiers and progresses accuracy at insignificant additional computational cost.
• d. Testing: In this stage the author uses the test set for prediction of gene sequence class.

Architecture of DNA/Gene Classification System

Experimental Design

• a. Dataset: ‘16S’ dataset has been used in this research which was downloaded from the RDP-II by NCBI. A total of 3000 sequences have been selected, and can be further clustered into 5 well-ordered taxonomic rank Family, Order, Class, Phylum and Genus by a consequent filtering stage.
• b. Evaluation Measures: Standard Deviation (SD) & Mean are calculated on 10 validation test folds.
• c. Hardware & Software Requirements: Python based Deep Learning libraries & Computer Vision will be oppressed for the project growth and its research. Training is performed on GPUs.

Conclusions

Deep learning models are powerful complement to traditional ML techniques and other analysis strategies. These approaches are used in a various application in computational biology, which includes image analysis and regulatory genomics. Research specifies that standard RNNs and its variations have improved performance in time-series data as when compared with other models. It is extensively used in the process of sequence data, like video description, text classification because RNNs can efficiently extract feature data from time-series data,

The main aim of this project was to evaluate how DL models could be functional in the classification of DNA sequences. Since gene annotation and gene prediction are crucial tasks to comprehend how the several genomes work, I want to contribute to the extent with few insights regarding trending technological methods. Every gene classification model that has any practice in the field of bioinformatics is required to achieve lots of features and also identify gene sequences. This further include, classification of homologous sequences and identification of other specific binding sites, terminator and regulatory regions, the identification of promoter within the genome.

In general, there are shared approaches between comparative methods and ab initio to augment classification results. With this report and work I wanted to measure and emphasize the usage of DL algorithms in the cracking of genomic problems. One issue that proved to be tough to overcome was the computational limits. DL projects typically distribute state of the art results by running huge information by consuming more time in clusters of dozens or hundreds or even thousands of high-end machines, and most of them use GPUs for matrix calculations.

RNNs in specific are popular in sequence classification problems with samples of variable length. Additional efforts at extracting more features from DNA sequences before feeding them to the models could also be made which results in overall calculations with more accuracy. The key enhancement would be in the working environment. With accomplishments like usage of GPU for calculations and the integration of our machine in a cluster that comprises other computers, hyperparameters like reduced learning rate can be improved, or increase size of the dataset. All of this possibly will result in improved inferences than those that are attained previously.

References

1. Juergen Schmid Huber. Deep Learning in Neural Networks: An Overview. Neural Networks
2. Oriol Vinyals, Ilya Sutskever and Quoc V Le. Sequence to sequence learning with neural networks
3. Alex Graves. Generating Sequences with RNN
4. Ritambhara Singh, Yanjun Qi and Deep Motif Dashboard: Visualizing and Understanding Genomic Sequences Using Deep Neural Networks. arXiv
5. Zachary C. Lipton. A Critical Review of RNN’s for Sequence Learning. arXiv