Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems—patient classification, fundamental biological processes and treatment of patients—and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique challenges. Following from an extensive literature review, we find that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art. Even though improvements over previous baselines have been modest in general, the recent progress indicates that deep learning methods will provide valuable means for speeding up or aiding human investigation. Though progress has been made linking a specific neural network's prediction to input features, understanding how users should interpret these models to make testable hypotheses about the system under study remains an open challenge. Furthermore, the limited amount of labelled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning enabling changes at both bench and bedside with the potential to transform several areas of biology and medicine.

Symbiotic bacteria often help their hosts acquire nutrients from their diet, showing trends of coevolution and independent acquisition by hosts from the same trophic levels. While these trends hint at important roles for biotic factors, the effects of the abiotic environment on symbiotic community composition remain comparably understudied. In this investigation, we examined the influence of abiotic and biotic factors on the gut bacterial communities of fish from different taxa, trophic levels and habitats. Phylogenetic and statistical analyses of 25 16S rRNA libraries revealed that salinity, trophic level and possibly host phylogeny shape the composition of fish gut bacteria. When analysed alongside bacterial communities from other environments, fish gut communities typically clustered with gut communities from mammals and insects. Similar consideration of individual phylotypes (vs. communities) revealed evolutionary ties between fish gut microbes and symbionts of animals, as many of the bacteria from the guts of herbivorous fish were closely related to those from mammals. Our results indicate that fish harbour more specialized gut communities than previously recognized. They also highlight a trend of convergent acquisition of similar bacterial communities by fish and mammals, raising the possibility that fish were the first to evolve symbioses resembling those found among extant gut fermenting mammals. Data accessibility DNA sequences of Poecilia reticulata gut bacteria: GenBank accession numbers JQ253406-JQ253517. Additional information regarding the metadata included in this paper is available in Tables S1 and S2 (Supporting information). Supporting informationAdditional supporting information may be found in the online version of this article. Table S1 Habitats, lifestyles, and phylogenetic affiliations of fish gut bacteria and their closest GenBank relatives. Table S2 List of primers used in all studies included in this meta-analysis. Fig. S1 Ordinal classifications of sequences from whole libraries of fish that were derived from culture independent methods.

Deep learning, which describes a class of machine learning algorithms, has recently showed impressive results across a variety of domains. Biology and medicine are data rich, but the data are complex and often ill-understood. Problems of this nature may be particularly well-suited to deep learning techniques. We examine applications of deep learning to a variety of biomedical problems—patient classification, fundamental biological processes, and treatment of patients—and discuss whether deep learning will transform these tasks or if the biomedical sphere poses unique challenges. We find that deep learning has yet to revolutionize or definitively resolve any of these problems, but promising advances have been made on the prior state of the art. Even when improvement over a previous baseline has been modest, we have seen signs that deep learning methods may speed or aid human investigation. More work is needed to address concerns related to interpretability and how to best model each problem. Furthermore, the limited amount of labeled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning powering changes at both bench and bedside with the potential to transform several areas of biology and medicine.

BackgroundOne of the main challenges in metagenomics is the identification of microorganisms in clinical and environmental samples. While an extensive and heterogeneous set of computational tools is available to classify microorganisms using whole-genome shotgun sequencing data, comprehensive comparisons of these methods are limited.ResultsIn this study, we use the largest-to-date set of laboratory-generated and simulated controls across 846 species to evaluate the performance of 11 metagenomic classifiers. Tools were characterized on the basis of their ability to identify taxa at the genus, species, and strain levels, quantify relative abundances of taxa, and classify individual reads to the species level. Strikingly, the number of species identified by the 11 tools can differ by over three orders of magnitude on the same datasets. Various strategies can ameliorate taxonomic misclassification, including abundance filtering, ensemble approaches, and tool intersection. Nevertheless, these strategies were often insufficient to completely eliminate false positives from environmental samples, which are especially important where they concern medically relevant species. Overall, pairing tools with different classification strategies (k-mer, alignment, marker) can combine their respective advantages.ConclusionsThis study provides positive and negative controls, titrated standards, and a guide for selecting tools for metagenomic analyses by comparing ranges of precision, accuracy, and recall. We show that proper experimental design and analysis parameters can reduce false positives, provide greater resolution of species in complex metagenomic samples, and improve the interpretation of results.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1299-7) contains supplementary material, which is available to authorized users.

Motivation: Datasets from high-throughput sequencing technologies have yielded a vast amount of data about organisms in environmental samples. Yet, it is still a challenge to assess the exact organism content in these samples because the task of taxonomic classification is too computationally complex to annotate all reads in a dataset. An easy-to-use webserver is needed to process these reads. While many methods exist, only a few are publicly available on webservers, and out of those, most do not annotate all reads.Results: We introduce a webserver that implements the naïve Bayes classifier (NBC) to classify all metagenomic reads to their best taxonomic match. Results indicate that NBC can assign next-generation sequencing reads to their taxonomic classification and can find significant populations of genera that other classifiers may miss.Availability: Publicly available at: http://nbc.ece.drexel.edu.Contact: gailr@ece.drexel.edu

Background: One of the main challenges in metagenomics is the identification of microorganisms in clinical and environmental samples. While an extensive and heterogeneous set of computational tools is available to classify microorganisms using whole-genome shotgun sequencing data, comprehensive comparisons of these methods are limited.

Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses.

BackgroundCurrently, the naïve Bayesian classifier provided by the Ribosomal Database Project (RDP) is one of the most widely used tools to classify 16S rRNA sequences, mainly collected from environmental samples. We show that RDP has 97+% assignment accuracy and is fast for 250 bp and longer reads when the read originates from a taxon known to the database. Because most environmental samples will contain organisms from taxa whose 16S rRNA genes have not been previously sequenced, we aim to benchmark how well the RDP classifier and other competing methods can discriminate these novel taxa from known taxa.Principal FindingsBecause each fragment is assigned a score (containing likelihood or confidence information such as the boostrap score in the RDP classifier), we “train” a threshold to discriminate between novel and known organisms and observe its performance on a test set. The threshold that we determine tends to be conservative (low sensitivity but high specificity) for naïve Bayesian methods. Nonetheless, our method performs better with the RDP classifier than the other methods tested, measured by the f-measure and the area-under-the-curve on the receiver operating characteristic of the test set. By constraining the database to well-represented genera, sensitivity improves 3–15%. Finally, we show that the detector is a good predictor to determine novel abundant taxa (especially for finer levels of taxonomy where novelty is more likely to be present).ConclusionsWe conclude that selecting a read-length appropriate RDP bootstrap score can significantly reduce the search space for identifying novel genera and higher levels in taxonomy. In addition, having a well-represented database significantly improves performance while having genera that are “highly” similar does not make a significant improvement. On a real dataset from an Amazon Terra Preta soil sample, we show that the detector can predict (or correlates to) whether novel sequences will be assigned to new taxa when the RDP database “doubles” in the future.