Task In Bioinformatics Research Articles

COS: A new MeSH term embedding incorporating corpus, ontology, and semantic predications.

The embedding of Medical Subject Headings (MeSH) terms has become a foundation for many downstream bioinformatics tasks. Recent studies employ different data sources, such as the corpus (in which each document is indexed by a set of MeSH terms), the MeSH term ontology, and the semantic predications between MeSH terms (extracted by SemMedDB), to learn their embeddings. While these data sources contribute to learning the MeSH term embeddings, current approaches fail to incorporate all of them in the learning process. The challenge is that the structured relationships between MeSH terms are different across the data sources, and there is no approach to fusing such complex data into the MeSH term embedding learning. In this paper, we study the problem of incorporating corpus, ontology, and semantic predications to learn the embeddings of MeSH terms. We propose a novel framework, Corpus, Ontology, and Semantic predications-based MeSH term embedding (COS), to generate high-quality MeSH term embeddings. COS converts the corpus, ontology, and semantic predications into MeSH term sequences, merges these sequences, and learns MeSH term embeddings using the sequences. Extensive experiments on different datasets show that COS outperforms various baseline embeddings and traditional non-embedding-based baselines.

The multiple alignments of very short sequences.

The multiple sequence alignment (MSA) is an increasingly important task in bioinformatics as we have to deal with the constantly increasing gene‐ and protein sequence databases. MSA is applied in phylogenetic analysis, in discovering conservative protein domains, in the assignment of secondary and tertiary structural features in proteins, or in the metagenomic sample analysis and gene discovery. Usually, the focus is on the MSA of long sequences, since in the practice these tasks appear most frequently. However, the strict analysis of the optimal MSA of short sequences is an area of negligence, and findings there may contribute to better and faster algorithms for the multiple alignment of long sequences. In the present contribution, we are examining length‐1 sequences using arbitrary metric and length‐2 sequences using unit metric, and we show that the optimum of the MSA problem can be achieved by the trivial alignment in both cases.

Implementation of Protein Sequence Classification for Globin family using Ensemble Learnin

Feature Extraction from protein sequence is a very important task in bioinformatics. The main focus of that work is protein sequences classification that can be used to improve drug discovery and identification of diseases for treating patients in the early stages of diagnosis. In this paper, we proposed a method which is used for feature extraction i.e. converting the protein sequence of hemoglobin in to feature vectors. The feature vectors are then given to the ensemble classifier as an input which uses various classifier to provide better result/performance as compared to any constituent learning algorithm alone.

Cancer Subtype Recognition Based on Laplacian Rank Constrained Multiview Clustering.

Integrating multigenomic data to recognize cancer subtype is an important task in bioinformatics. In recent years, some multiview clustering algorithms have been proposed and applied to identify cancer subtype. However, these clustering algorithms ignore that each data contributes differently to the clustering results during the fusion process, and they require additional clustering steps to generate the final labels. In this paper, a new one-step method for cancer subtype recognition based on graph learning framework is designed, called Laplacian Rank Constrained Multiview Clustering (LRCMC). LRCMC first forms a graph for a single biological data to reveal the relationship between data points and uses affinity matrix to encode the graph structure. Then, it adds weights to measure the contribution of each graph and finally merges these individual graphs into a consensus graph. In addition, LRCMC constructs the adaptive neighbors to adjust the similarity of sample points, and it uses the rank constraint on the Laplacian matrix to ensure that each graph structure has the same connected components. Experiments on several benchmark datasets and The Cancer Genome Atlas (TCGA) datasets have demonstrated the effectiveness of the proposed algorithm comparing to the state-of-the-art methods.

PHONI: Streamed Matching Statistics with Multi-Genome References.

Computing the matching statistics of patterns with respect to a text is a fundamental task in bioinformatics, but a formidable one when the text is a highly compressed genomic database. Bannai et al. gave an efficient solution for this case, which Rossi et al. recently implemented, but it uses two passes over the patterns and buffers a pointer for each character during the first pass. In this paper, we simplify their solution and make it streaming, at the cost of slowing it down slightly. This means that, first, we can compute the matching statistics of several long patterns (such as whole human chromosomes) in parallel while still using a reasonable amount of RAM; second, we can compute matching statistics online with low latency and thus quickly recognize when a pattern becomes incompressible relative to the database. Our code is available at https://github.com/koeppl/phoni.

ILearnPlus: a comprehensive and automated machine-learning platform for nucleic acid and protein sequence analysis, prediction and visualization.

Sequence-based analysis and prediction are fundamental bioinformatic tasks that facilitate understanding of the sequence(-structure)-function paradigm for DNAs, RNAs and proteins. Rapid accumulation of sequences requires equally pervasive development of new predictive models, which depends on the availability of effective tools that support these efforts. We introduce iLearnPlus, the first machine-learning platform with graphical- and web-based interfaces for the construction of machine-learning pipelines for analysis and predictions using nucleic acid and protein sequences. iLearnPlus provides a comprehensive set of algorithms and automates sequence-based feature extraction and analysis, construction and deployment of models, assessment of predictive performance, statistical analysis, and data visualization; all without programming. iLearnPlus includes a wide range of feature sets which encode information from the input sequences and over twenty machine-learning algorithms that cover several deep-learning approaches, outnumbering the current solutions by a wide margin. Our solution caters to experienced bioinformaticians, given the broad range of options, and biologists with no programming background, given the point-and-click interface and easy-to-follow design process. We showcase iLearnPlus with two case studies concerning prediction of long noncoding RNAs (lncRNAs) from RNA transcripts and prediction of crotonylation sites in protein chains. iLearnPlus is an open-source platform available at https://github.com/Superzchen/iLearnPlus/ with the webserver at http://ilearnplus.erc.monash.edu/.

Application of learning to rank in bioinformatics tasks.

Over the past decades, learning to rank (LTR) algorithms have been gradually applied to bioinformatics. Such methods have shown significant advantages in multiple research tasks in this field. Therefore, it is necessary to summarize and discuss the application of these algorithms so that these algorithms are convenient and contribute to bioinformatics. In this paper, the characteristics of LTR algorithms and their strengths over other types of algorithms are analyzed based on the application of multiple perspectives in bioinformatics. Finally, the paper further discusses the shortcomings of the LTR algorithms, the methods and means to better use the algorithms and some open problems that currently exist.

Bladder cancer in the time of machine learning: Intelligent tools for diagnosis and management.

Machine learning (ML) is the subfield of artificial intelligence (AI), born from the marriage between statistics and computer science, with the unique purpose of building prediction algorithms able to improve their performances by automatically learning from massive data sets. The availability of ever-growing computational power and highly evolved pattern recognition software has led to the spread of ML-based systems able to perform complex tasks in bioinformatics, medical imaging, and diagnostics. These intelligent tools could be the answer to the unmet need for non-invasive and patient-tailored instruments for the diagnosis and management of bladder cancer (BC), which are still based on old technologies and unchanged nomograms. We reviewed the most significant evidence on ML in the diagnosis, prognosis, and management of bladder cancer, to find out if these intelligent technologies are ready to be introduced into the daily clinical practice of the urologist.

Identifying Native and Non-native Membrane Protein Loops by Using Stabilizing Energetic Terms of Three Popular Force Fields

Background: Predicting the three-dimensional structure of globular proteins from their amino acid sequence has reached a fair accuracy, but predicting the structure of membrane proteins, especially loop regions, is still a difficult task in structural bioinformatics. The difficulty in predicting membrane loops is due to various factors like length variation, position, flexibility, and they are easily prone to mutation. Objective: In the present work, we address the problem of identifying and ranking near-native loops from a set of decoys generated by Monte-Carlo simulations. Methods: We systematically analyzed native and generated non-native decoys to develop a scoring function. The scoring function uses four important stabilizing energy terms from three popular force fields, such as FOLDX, OPLS, and AMBER, to identify and rank near-native membrane loops. Results: The results reveal better discrimination of native and non-natives and perform poor prediction in binary classifying native and near-native defined based on Root Mean Square Deviation (RMSD), Global Distance Test (GDT), and Template Modeling (TM) score, respectively. Conclusions: From our observations, we conclude that the important energy features described here may help to improve the loop prediction when the membrane protein database size increases.

A Deep Convolutional Neural Network to Improve the Prediction of Protein Secondary Structure

Background: Protein secondary structure prediction (PSSP) is a fundamental task in bioinformatics that is helpful for understanding the three-dimensional structure and biological function of proteins. Many neural network-based prediction methods have been developed for protein secondary structures. Deep learning and multiple features are two obvious means to improve prediction accuracy. Objective: To promote the development of PSSP, a deep convolutional neural network-based method is proposed to predict both the eight-state and three-state of protein secondary structure. Methods: In this model, sequence and evolutionary information of proteins are combined as multiple input features after preprocessing. A deep convolutional neural network with no pooling layer and connection layer is then constructed to predict the secondary structure of proteins. L2 regularization, batch normalization, and dropout techniques are employed to avoid over-fitting and obtain better prediction performance, and an improved cross-entropy is used as the loss function. Results: Our proposed model can obtain Q3 prediction results of 86.2%, 84.5%, 87.8%, and 84.7%, respectively, on CullPDB, CB513, CASP10 and CASP11 datasets, with corresponding Q8 prediction results of 74.1%, 70.5%, 74.9%, and 71.3%. Conclusion: We have proposed the DCNN-SS deep convolutional-network-based PSSP method, and experimental results show that DCNN-SS performs competitively with other methods.

RepeatFS: a file system providing reproducibility through provenance and automation.

MotivationReproducibility is of central importance to the scientific process. The difficulty of consistently replicating and verifying experimental results is magnified in the era of big data, in which bioinformatics analysis often involves complex multi-application pipelines operating on terabytes of data. These processes result in thousands of possible permutations of data preparation steps, software versions and command-line arguments. Existing reproducibility frameworks are cumbersome and involve redesigning computational methods. To address these issues, we developed RepeatFS, a file system that records, replicates and verifies informatics workflows with no alteration to the original methods. RepeatFS also provides several other features to help promote analytical transparency and reproducibility, including provenance visualization and task automation.ResultsWe used RepeatFS to successfully visualize and replicate a variety of bioinformatics tasks consisting of over a million operations with no alteration to the original methods. RepeatFS correctly identified all software inconsistencies that resulted in replication differences.Availabilityand implementationRepeatFS is implemented in Python 3. Its source code and documentation are available at https://github.com/ToniWestbrook/repeatfs.Supplementary information Supplementary data are available at Bioinformatics online.

Intron retention and its impact on gene expression and protein diversity: A review and a practical guide.

Intron retention (IR) occurs when a complete and unspliced intron remains in mature mRNA. An increasing body of literature has demonstrated a major role for IR in numerous biological functions, including several that impact human health and disease. Although experimental technologies used to study other forms of mRNA splicing can also be used to investigate IR, a specialized downstream computational analysis is optimal for IR discovery and analysis. Here we provide a review of IR and its biological implications, as well as a practical guide for how to detect and analyze it. Several methods, including long read third generation direct RNA sequencing, are described. We have developed an R package, FakIR, to facilitate the execution of the bioinformatic tasks recommended in this review and a tutorial on how to fit them to users aims. Additionally, we provide guidelines and experimental protocols to validate IR discovery and to evaluate the potential impact of IR on gene expression and protein output. This article is categorized under: RNA Evolution and Genomics > Computational Analyses of RNA RNA Processing > Splicing Regulation/Alternative Splicing RNA Methods > RNA Analyses in vitro and In Silico.

A Generalized Iterative Map for Analysis of Protein Sequences.

The similarities comparison of biological sequences is an important task in bioinformatics. The methods of the similarities comparison for biological sequences are divided into two classes: sequence alignment method and alignment-free method. The graphical representation of biological sequences is a kind of alignment-free method, which constitutes a tool for analyzing and visualizing the biological sequences. In this article, a generalized iterative map of protein sequences was suggested to analyze the similarities of biological sequences. Based on the normalized physicochemical indexes of 20 amino acids, each amino acid can be mapped into a point in 5D space. A generalized iterative function system was introduced to outline a generalized iterative map of protein sequences, which can not only reflect various physicochemical properties of amino acids but also incorporate with different compression ratios of the component of a generalized iterative map. Several properties were proved to illustrate the advantage of the generalized iterative map. The mathematical description of the generalized iterative map was suggested to compare the similarities and dissimilarities of protein sequences. Based on this method, similarities/dissimilarities were compared among ND5 protein sequences, as well as ND6 protein sequences of ten different species. By correlation analysis, the ClustalW results were compared with our similarity/dissimilarity results and other graphical representation results to show the utility of our approach. The comparison results show that our approach has better correlations with ClustalW for all species than other approaches and illustrate the effectiveness of our approach. Two examples show that our method not only has good performances and effects in the similarity/dissimilarity analysis of protein sequences but also does not require complex computation.

Protein class prediction based on Count Vectorizer and long short term memory

Proteins class and function prediction is one of the most significant task in computational bioinformatics. The information about the protein functions and class plays a vital role in understanding biological cells and has a great impact on human life in factors such as personalized medicine. The technical advancement in the areas of biological aspects and understanding of biological processes results in features and characteristics of important Proteins. Prediction of amino acid sequence involves prediction of amino sequence folding and its structures from the primary sequence obtained. In this work, Machine learning prediction algorithms have applied for protein class prediction. This method takes consideration of macromolecules of biological significances. Later the solution focuses on the understanding of different protein family, subsequently classify the protein family type sequence. This is achieved through machine learning algorithms Naive Bayes (NB) and Random forest (RF) algorithms with count vectorized feature and LSTM. These algorithms are used to classify the protein family on its protein sequence. Finally, result shows that LSTM predicts the protein class more accurately than the RF, and NB algorithm. LSTM achieves an accuracy of 96% whereas RF & NB with an accuracy of 91% and 86%.

Embedding covariate adjustments in tree-based automated machine learning for biomedical big data analyses

BackgroundA typical task in bioinformatics consists of identifying which features are associated with a target outcome of interest and building a predictive model. Automated machine learning (AutoML) systems such as the Tree-based Pipeline Optimization Tool (TPOT) constitute an appealing approach to this end. However, in biomedical data, there are often baseline characteristics of the subjects in a study or batch effects that need to be adjusted for in order to better isolate the effects of the features of interest on the target. Thus, the ability to perform covariate adjustments becomes particularly important for applications of AutoML to biomedical big data analysis.ResultsWe developed an approach to adjust for covariates affecting features and/or target in TPOT. Our approach is based on regressing out the covariates in a manner that avoids ‘leakage’ during the cross-validation training procedure. We describe applications of this approach to toxicogenomics and schizophrenia gene expression data sets. The TPOT extensions discussed in this work are available at https://github.com/EpistasisLab/tpot/tree/v0.11.1-resAdj.ConclusionsIn this work, we address an important need in the context of AutoML, which is particularly crucial for applications to bioinformatics and medical informatics, namely covariate adjustments. To this end we present a substantial extension of TPOT, a genetic programming based AutoML approach. We show the utility of this extension by applications to large toxicogenomics and differential gene expression data. The method is generally applicable in many other scenarios from the biomedical field.

Gsufsort: constructing suffix arrays, LCP arrays and BWTs for string collections

BackgroundThe construction of a suffix array for a collection of strings is a fundamental task in Bioinformatics and in many other applications that process strings. Related data structures, as the Longest Common Prefix array, the Burrows–Wheeler transform, and the document array, are often needed to accompany the suffix array to efficiently solve a wide variety of problems. While several algorithms have been proposed to construct the suffix array for a single string, less emphasis has been put on algorithms to construct suffix arrays for string collections.ResultIn this paper we introduce gsufsort, an open source software for constructing the suffix array and related data indexing structures for a string collection with N symbols in O(N) time. Our tool is written in ANSI/C and is based on the algorithm gSACA-K (Louza et al. in Theor Comput Sci 678:22–39, 2017), the fastest algorithm to construct suffix arrays for string collections. The tool supports large fasta, fastq and text files with multiple strings as input. Experiments have shown very good performance on different types of strings.Conclusionsgsufsort is a fast, portable, and lightweight tool for constructing the suffix array and additional data structures for string collections.

Protein function prediction is improved by creating synthetic feature samples with generative adversarial networks

Protein function prediction is a challenging but important task in bioinformatics. Many prediction methods have been developed, but are still limited by the bottleneck on training sample quantity. Therefore, it is valuable to develop a data augmentation method that can generate high-quality synthetic samples to further improve the accuracy of prediction methods. In this work, we propose a novel generative adversarial networks-based method, FFPred-GAN, to accurately learn the high-dimensional distributions of protein sequence-based biophysical features and also generate high-quality synthetic protein feature samples. The experimental results suggest that the synthetic protein feature samples are successful in improving the prediction accuracy for all three domains of Gene Ontology through augmentation of the original training protein feature samples. Training machine learning models to predict the function of proteins is limited by the availability of only a small amount of labelled training data. Training can be improved by employing generative adversarial networks to generate additional synthetic protein samples.

Pangenome Graphs.

Low-cost whole-genome assembly has enabled the collection of haplotype-resolved pangenomes for numerous organisms. In turn, this technological change is encouraging the development of methods that can precisely address the sequence and variation described in large collections of related genomes. These approaches often use graphical models of the pangenome to support algorithms for sequence alignment, visualization, functional genomics, and association studies. The additional information provided to these methods by the pangenome allows them to achieve superior performance on a variety of bioinformatic tasks, including read alignment, variant calling, and genotyping. Pangenome graphs stand to become a ubiquitous tool in genomics. Although it is unclear whether they will replace linearreference genomes, their ability to harmoniously relate multiple sequence and coordinate systems will make them useful irrespective of which pangenomic models become most common in the future.

Boosting the accuracy of protein secondary structure prediction through nearest neighbor search and method hybridization

Motivation Protein secondary structure prediction is a fundamental precursor to many bioinformatics tasks. Nearly all state-of-the-art tools when computing their secondary structure prediction do not explicitly leverage the vast number of proteins whose structure is known. Leveraging this additional information in a so-called template-based method has the potential to significantly boost prediction accuracy. Method We present a new hybrid approach to secondary structure prediction that gains the advantages of both template- and non-template-based methods. Our core template-based method is an algorithmic approach that uses metric-space nearest neighbor search over a template database of fixed-length amino acid words to determine estimated class-membership probabilities for each residue in the protein. These probabilities are then input to a dynamic programming algorithm that finds a physically valid maximum-likelihood prediction for the entire protein. Our hybrid approach exploits a novel accuracy estimator for our core method, which estimates the unknown true accuracy of its prediction, to discern when to switch between template- and non-template-based methods. Results On challenging CASP benchmarks, the resulting hybrid approach boosts the state-of-the-art Q8 accuracy by more than 2-10%, and Q3 accuracy by more than 1-3%, yielding the most accurate method currently available for both 3- and 8-state secondary structure prediction. Availability and implementation A preliminary implementation in a new tool we call Nnessy is available free for non-commercial use at http://nnessy.cs.arizona.edu.

A novel alignment-free DNA sequence similarity analysis approach based on top-k n-gram match-up

DNA sequence similarity analysis is an essential task in computational biology and bioinformatics. In nearly all research that explores evolutionary relationships, gene function analysis, protein structure prediction and sequence retrieving, it is necessary to perform similarity calculations. As an alternative to alignment-based sequence comparison methods, which result in high computational cost, alignment-free methods have emerged that calculate similarity by digitizing the sequence in a different space. In this paper, we proposed an alignment-free DNA sequence similarity analysis method based on top-k n-gram matches, with the prediction that common repeating DNA subsections indicate high similarity between DNA sequences. In our method, we determined DNA sequence similarities by measuring similarity among feature vectors created according to top-k n-gram match-up scores without the use of similarity functions. We applied the similarity calculation for three different DNA data sets of different lengths. The phylogenetic relationships revealed by our method show that our trees coincide almost completely with the results of the MEGA software, which is based on sequence alignment. Our findings show that a certain number of frequently recurring common sequence patterns have the power to characterize DNA sequences.