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  1. Abstract

    Sequence classification facilitates a fundamental understanding of the structure of microbial communities. Binary metagenomic sequence classifiers are insufficient because environmental metagenomes are typically derived from multiple sequence sources. Here we introduce a deep-learning based sequence classifier, DeepMicroClass, that classifies metagenomic contigs into five sequence classes, i.e. viruses infecting prokaryotic or eukaryotic hosts, eukaryotic or prokaryotic chromosomes, and prokaryotic plasmids. DeepMicroClass achieved high performance for all sequence classes at various tested sequence lengths ranging from 500 bp to 100 kbps. By benchmarking on a synthetic dataset with variable sequence class composition, we showed that DeepMicroClass obtained better performance for eukaryotic, plasmid and viral contig classification than other state-of-the-art predictors. DeepMicroClass achieved comparable performance on viral sequence classification with geNomad and VirSorter2 when benchmarked on the CAMI II marine dataset. Using a coastal daily time-series metagenomic dataset as a case study, we showed that microbial eukaryotes and prokaryotic viruses are integral to microbial communities. By analyzing monthly metagenomes collected at HOT and BATS, we found relatively higher viral read proportions in the subsurface layer in late summer, consistent with the seasonal viral infection patterns prevalent in these areas. We expect DeepMicroClass will promote metagenomic studies of under-appreciated sequence types.

     
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  2. Abstract Motivation

    Phage–host associations play important roles in microbial communities. But in natural communities, as opposed to culture-based lab studies where phages are discovered and characterized metagenomically, their hosts are generally not known. Several programs have been developed for predicting which phage infects which host based on various sequence similarity measures or machine learning approaches. These are often based on whole viral and host genomes, but in metagenomics-based studies, we rarely have whole genomes but rather must rely on contigs that are sometimes as short as hundreds of bp long. Therefore, we need programs that predict hosts of phage contigs on the basis of these short contigs. Although most existing programs can be applied to metagenomic datasets for these predictions, their accuracies are generally low. Here, we develop ContigNet, a convolutional neural network-based model capable of predicting phage–host matches based on relatively short contigs, and compare it to previously published VirHostMatcher (VHM) and WIsH.

    Results

    On the validation set, ContigNet achieves 72–85% area under the receiver operating characteristic curve (AUROC) scores, compared to the maximum of 68% by VHM or WIsH for contigs of lengths between 200 bps to 50 kbps. We also apply the model to the Metagenomic Gut Virus (MGV) catalogue, a dataset containing a wide range of draft genomes from metagenomic samples and achieve 60–70% AUROC scores compared to that of VHM and WIsH of 52%. Surprisingly, ContigNet can also be used to predict plasmid-host contig associations with high accuracy, indicating a similar genetic exchange between mobile genetic elements and their hosts.

    Availability and implementation

    The source code of ContigNet and related datasets can be downloaded from https://github.com/tianqitang1/ContigNet.

     
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  3. null (Ed.)