Higher-order Markov models for metagenomic sequence classification

2020 ◽  
Vol 36 (14) ◽  
pp. 4130-4136
Author(s):  
David J Burks ◽  
Rajeev K Azad
Keyword(s):  
Dna Sequences ◽  
Markov Models ◽  
Fragment Size ◽  
Higher Order ◽  
Training Data ◽  
Supplementary Information ◽  
Local Alignment ◽  
Metagenomic Sequence ◽  
Higher Order Models

Abstract Motivation Alignment-free, stochastic models derived from k-mer distributions representing reference genome sequences have a rich history in the classification of DNA sequences. In particular, the variants of Markov models have previously been used extensively. Higher-order Markov models have been used with caution, perhaps sparingly, primarily because of the lack of enough training data and computational power. Advances in sequencing technology and computation have enabled exploitation of the predictive power of higher-order models. We, therefore, revisited higher-order Markov models and assessed their performance in classifying metagenomic sequences. Results Comparative assessment of higher-order models (HOMs, 9th order or higher) with interpolated Markov model, interpolated context model and lower-order models (8th order or lower) was performed on metagenomic datasets constructed using sequenced prokaryotic genomes. Our results show that HOMs outperform other models in classifying metagenomic fragments as short as 100 nt at all taxonomic ranks, and at lower ranks when the fragment size was increased to 250 nt. HOMs were also found to be significantly more accurate than local alignment which is widely relied upon for taxonomic classification of metagenomic sequences. A novel software implementation written in C++ performs classification faster than the existing Markovian metagenomic classifiers and can therefore be used as a standalone classifier or in conjunction with existing taxonomic classifiers for more robust classification of metagenomic sequences. Availability and implementation The software has been made available at https://github.com/djburks/SMM. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals MODER2: first-order Markov modeling and discovery of monomeric and dimeric binding motifs

2020 ◽  
Vol 36 (9) ◽  
pp. 2690-2696
Author(s):  
Jarkko Toivonen ◽  
Pratyush K Das ◽  
Jussi Taipale ◽  
Esko Ukkonen
Keyword(s):  
Markov Models ◽  
Expectation Maximization Algorithm ◽  
Software Tool ◽  
Specific Weight ◽  
Training Data ◽  
Supplementary Information ◽  
Markov Modeling ◽  
Binding Motifs ◽  
The Difference ◽  
Probability Matrices

Abstract Motivation Position-specific probability matrices (PPMs, also called position-specific weight matrices) have been the dominating model for transcription factor (TF)-binding motifs in DNA. There is, however, increasing recent evidence of better performance of higher order models such as Markov models of order one, also called adjacent dinucleotide matrices (ADMs). ADMs can model dependencies between adjacent nucleotides, unlike PPMs. A modeling technique and software tool that would estimate such models simultaneously both for monomers and their dimers have been missing. Results We present an ADM-based mixture model for monomeric and dimeric TF-binding motifs and an expectation maximization algorithm MODER2 for learning such models from training data and seeds. The model is a mixture that includes monomers and dimers, built from the monomers, with a description of the dimeric structure (spacing, orientation). The technique is modular, meaning that the co-operative effect of dimerization is made explicit by evaluating the difference between expected and observed models. The model is validated using HT-SELEX and generated datasets, and by comparing to some earlier PPM and ADM techniques. The ADM models explain data slightly better than PPM models for 314 tested TFs (or their DNA-binding domains) from four families (bHLH, bZIP, ETS and Homeodomain), the ADM mixture models by MODER2 being the best on average. Availability and implementation Software implementation is available from https://github.com/jttoivon/moder2. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals A framework for space-efficient variable-order Markov models

2019 ◽  
Vol 35 (22) ◽  
pp. 4607-4616
Author(s):  
Fabio Cunial ◽  
Jarno Alanko ◽  
Djamal Belazzougui
Keyword(s):  
Language Processing ◽  
Data Structures ◽  
Markov Models ◽  
Biological Properties ◽  
Specific Model ◽  
Suffix Array ◽  
Training Data ◽  
Supplementary Information ◽  
Variable Order ◽  
Scoring Functions

Abstract Motivation Markov models with contexts of variable length are widely used in bioinformatics for representing sets of sequences with similar biological properties. When models contain many long contexts, existing implementations are either unable to handle genome-scale training datasets within typical memory budgets, or they are optimized for specific model variants and are thus inflexible. Results We provide practical, versatile representations of variable-order Markov models and of interpolated Markov models, that support a large number of context-selection criteria, scoring functions, probability smoothing methods, and interpolations, and that take up to four times less space than previous implementations based on the suffix array, regardless of the number and length of contexts, and up to ten times less space than previous trie-based representations, or more, while matching the size of related, state-of-the-art data structures from Natural Language Processing. We describe how to further compress our indexes to a quantity related to the redundancy of the training data, saving up to 90% of their space on very repetitive datasets, and making them become up to 60 times smaller than previous implementations based on the suffix array. Finally, we show how to exploit constraints on the length and frequency of contexts to further shrink our compressed indexes to half of their size or more, achieving data structures that are a hundred times smaller than previous implementations based on the suffix array, or more. This allows variable-order Markov models to be used with bigger datasets and with longer contexts on the same hardware, thus possibly enabling new applications. Availability and implementation https://github.com/jnalanko/VOMM Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Metabolic network-guided binning of metagenomic sequence fragments

2015 ◽  
Vol 32 (6) ◽  
pp. 867-874 ◽  
Author(s):  
Matthew B. Biggs ◽  
Jason A. Papin
Keyword(s):  
Metabolic Network ◽  
Dna Sequences ◽  
Metabolic Networks ◽  
Human Microbiome ◽  
Environmental Dna ◽  
Human Microbiome Project ◽  
Supplementary Information ◽  
Metagenomic Sequence ◽  
Connectivity Score ◽  
Genome Scale

Abstract Motivation: Most microbes on Earth have never been grown in a laboratory, and can only be studied through DNA sequences. Environmental DNA sequence samples are complex mixtures of fragments from many different species, often unknown. There is a pressing need for methods that can reliably reconstruct genomes from complex metagenomic samples in order to address questions in ecology, bioremediation, and human health. Results: We present the SOrting by NEtwork Completion (SONEC) approach for assigning reactions to incomplete metabolic networks based on a metabolite connectivity score. We successfully demonstrate proof of concept in a set of 100 genome-scale metabolic network reconstructions, and delineate the variables that impact reaction assignment accuracy. We further demonstrate the integration of SONEC with existing approaches (such as cross-sample scaffold abundance profile clustering) on a set of 94 metagenomic samples from the Human Microbiome Project. We show that not only does SONEC aid in reconstructing species-level genomes, but it also improves functional predictions made with the resulting metabolic networks. Availability and implementation: The datasets and code presented in this work are available at: https://bitbucket.org/mattbiggs/sorting_by_network_completion/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

scholarly journals FOCUS2: agile and sensitive classification of metagenomics data using a reduced database

2016 ◽  
Author(s):  
Genivaldo Gueiros Z. Silva ◽  
Bas E. Dutilh ◽  
Robert A. Edwards
Keyword(s):  
Microbial Community ◽  
Dna Sequences ◽  
Computational Method ◽  
Environmental Research ◽  
Supplementary Information ◽  
Sequence Classification ◽  
Computationally Efficient ◽  
Link Type ◽  
Metagenomics Data

ABSTRACTSummaryMetagenomics approaches rely on identifying the presence of organisms in the microbial community from a set of unknown DNA sequences. Sequence classification has valuable applications in multiple important areas of medical and environmental research. Here we introduce FOCUS2, an update of the previously published computational method FOCUS. FOCUS2 was tested with 10 simulated and 543 real metagenomes demonstrating that the program is more sensitive, faster, and more computationally efficient than existing methods.AvailabilityThe Python implementation is freely available at https://edwards.sdsu.edu/FOCUS2.Supplementary informationavailable at Bioinformatics online.

Semi-supervised learning of Hidden Markov Models for biological sequence analysis

2018 ◽  
Vol 35 (13) ◽  
pp. 2208-2215 ◽  
Author(s):  
Ioannis A Tamposis ◽  
Konstantinos D Tsirigos ◽  
Margarita C Theodoropoulou ◽  
Panagiota I Kontou ◽  
Pantelis G Bagos
Keyword(s):  
Sequence Analysis ◽  
Supervised Learning ◽  
Hidden Markov Models ◽  
Markov Models ◽  
Hidden Markov ◽  
Transmembrane Protein ◽  
Training Data ◽  
Supplementary Information ◽  
Training Procedure ◽  
Partially Labeled Data

Abstract Motivation Hidden Markov Models (HMMs) are probabilistic models widely used in applications in computational sequence analysis. HMMs are basically unsupervised models. However, in the most important applications, they are trained in a supervised manner. Training examples accompanied by labels corresponding to different classes are given as input and the set of parameters that maximize the joint probability of sequences and labels is estimated. A main problem with this approach is that, in the majority of the cases, labels are hard to find and thus the amount of training data is limited. On the other hand, there are plenty of unclassified (unlabeled) sequences deposited in the public databases that could potentially contribute to the training procedure. This approach is called semi-supervised learning and could be very helpful in many applications. Results We propose here, a method for semi-supervised learning of HMMs that can incorporate labeled, unlabeled and partially labeled data in a straightforward manner. The algorithm is based on a variant of the Expectation-Maximization (EM) algorithm, where the missing labels of the unlabeled or partially labeled data are considered as the missing data. We apply the algorithm to several biological problems, namely, for the prediction of transmembrane protein topology for alpha-helical and beta-barrel membrane proteins and for the prediction of archaeal signal peptides. The results are very promising, since the algorithms presented here can significantly improve the prediction performance of even the top-scoring classifiers. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Casboundary: automated definition of integral Cas cassettes

2020 ◽  
Author(s):  
Victor A Padilha ◽  
Omer S Alkhnbashi ◽  
Van Dinh Tran ◽  
Shiraz A Shah ◽  
André C P L F Carvalho ◽  
...  
Keyword(s):  
Markov Models ◽  
Hidden Markov ◽  
Predictive Performance ◽  
Research Field ◽  
Supplementary Information ◽  
Bacterial Genomes ◽  
Average Similarity ◽  
Cas Genes ◽  
Definition Of

Abstract Motivation CRISPR-Cas are important systems found in most archaeal and many bacterial genomes, providing adaptive immunity against mobile genetic elements in prokaryotes. The CRISPR-Cas systems are encoded by a set of consecutive cas genes, here termed cassette. The identification of cassette boundaries is key for finding cassettes in CRISPR research field. This is often carried out by using Hidden Markov Models and manual annotation. In this article, we propose the first method able to automatically define the cassette boundaries. In addition, we present a Cas-type predictive model used by the method to assign each gene located in the region defined by a cassette’s boundaries a Cas label from a set of pre-defined Cas types. Furthermore, the proposed method can detect potentially new cas genes and decompose a cassette into its modules. Results We evaluate the predictive performance of our proposed method on data collected from the two most recent CRISPR classification studies. In our experiments, we obtain an average similarity of 0.86 between the predicted and expected cassettes. Besides, we achieve F-scores above 0.9 for the classification of cas genes of known types and 0.73 for the unknown ones. Finally, we conduct two additional study cases, where we investigate the occurrence of potentially new cas genes and the occurrence of module exchange between different genomes. Availability and implementation https://github.com/BackofenLab/Casboundary. Contact [email protected] or [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

The Modified DNA Identification Classification on Fuzzy Relation

2011 ◽  
Vol 48-49 ◽  
pp. 1275-1281 ◽  
Author(s):  
Yu Jen Hu ◽  
Yuh Hua Hu ◽  
Jyh Bin Ke
Keyword(s):  
Machine Learning ◽  
Dna Sequences ◽  
Fuzzy Relation ◽  
Fuzzy Cluster ◽  
Training Data ◽  
Dna Identification ◽  
Modified Dna

We proposed a categorized method of DNA sequences matrix by FCM (fuzzy cluster means). FCM avoided the errors caused by the reduction of dimensions. It further reached comprehensive machine learning. In our experiment, there are 40 training data which are artificial samples, and we verify the proposed method with 182 natural DNA sequences. The result showed the proposed method enhanced the accuracy of the classification of genes from 76% to 93%.

scholarly journals A deep learning approach to pattern recognition for short DNA sequences

2018 ◽  
Author(s):  
Akosua Busia ◽  
George E. Dahl ◽  
Clara Fannjiang ◽  
David H. Alexander ◽  
Elizabeth Dorfman ◽  
...  
Keyword(s):  
Deep Learning ◽  
Dna Sequences ◽  
Distinct Species ◽  
Training Data ◽  
Supplementary Information ◽  
Learning Approach ◽  
Biological Sequences ◽  
Public Research ◽  
Species Classification ◽  
Link Type

AbstractMotivationInferring properties of biological sequences--such as determining the species-of-origin of a DNA sequence or the function of an amino-acid sequence--is a core task in many bioinformatics applications. These tasks are often solved using string-matching to map query sequences to labeled database sequences or via Hidden Markov Model-like pattern matching. In the current work we describe and assess an deep learning approach which trains a deep neural network (DNN) to predict database-derived labels directly from query sequences.ResultsWe demonstrate this DNN performs at state-of-the-art or above levels on a difficult, practically important problem: predicting species-of-origin from short reads of 16S ribosomal DNA. When trained on 16S sequences of over 13,000 distinct species, our DNN achieves read-level species classification accuracy within 2.0% of perfect memorization of training data, and produces more accurate genus-level assignments for reads from held-out species thank-mer, alignment, and taxonomic binning baselines. Moreover, our models exhibit greater robustness than these existing approaches to increasing noise in the query sequences. Finally, we show that these DNNs perform well on experimental 16S mock community dataset. Overall, our results constitute a first step towards our long-term goal of developing a general-purpose deep learning approach to predicting meaningful labels from short biological sequences.AvailabilityTensorFlow training code is available through GitHub (https://github.com/tensorflow/models/tree/master/research). Data in TensorFlow TFRecord format is available on Google Cloud Storage (gs://brain-genomics-public/research/seq2species/)[email protected] informationSupplementary data are available in a separate document.

scholarly journals BERTax: taxonomic classification of DNA sequences with Deep Neural Networks

2021 ◽  
Author(s):  
Florian Mock ◽  
Fleming Kretschmer ◽  
Anton Kriese ◽  
Sebastian Böcker ◽  
Manja Marz
Keyword(s):  
Language Processing ◽  
Dna Sequences ◽  
Information Gain ◽  
Taxonomic Classification ◽  
Training Data ◽  
Misclassification Rate ◽  
Genomic Sequences ◽  
Similar Species ◽  
Common Task

Taxonomic classification, i.e., the identification and assignment to groups of biological organisms with the same origin and characteristics, is a common task in genetics. Nowadays, taxonomic classification is mainly based on genome similarity search to large genome databases. In this process, the classification quality depends heavily on the database since representative relatives have to be known already. Many genomic sequences cannot be classified at all or only with a high misclassification rate. Here we present BERTax, a program that uses a deep neural network to precisely classify the superkingdom, phylum, and genus of DNA sequences taxonomically without the need for a known representative relative from a database. For this, BERTax uses the natural language processing model BERT trained to represent DNA. We show BERTax to be at least on par with the state-of-the-art approaches when taxonomically similar species are part of the training data. In case of an entirely novel organism, however, BERTax clearly outperforms any existing approach. Finally, we show that BERTax can also be combined with database approaches to further increase the prediction quality. Since BERTax is not based on homologous entries in databases, it allows precise taxonomic classification of a broader range of genomic sequences. This leads to a higher number of correctly classified sequences and thus increases the overall information gain.

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