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Hierarchical Hidden Markov models enable accurate and diverse detection of antimicrobial resistance sequences.

ABSTRACT: The characterization of antimicrobial resistance genes from high-throughput sequencing data has become foundational in public health research and regulation. This requires mapping sequence reads to databases of known antimicrobial resistance genes to determine the genes present in the sample. Mapping sequence reads to known genes is traditionally accomplished using alignment. Alignment methods have high specificity but are limited in their ability to detect sequences that are divergent from the reference database, which can result in a substantial false negative rate. We address this shortcoming through the creation of Meta-MARC, which enables detection of diverse resistance sequences using hierarchical, DNA-based Hidden Markov Models. We first describe Meta-MARC and then demonstrate its efficacy on simulated and functional metagenomic datasets. Meta-MARC has higher sensitivity relative to competing methods. This sensitivity allows for detection of sequences that are divergent from known antimicrobial resistance genes. This functionality is imperative to expanding existing antimicrobial gene databases.

SUBMITTER: Lakin SM

PROVIDER: S-EPMC6684577 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Hierarchical Hidden Markov models enable accurate and diverse detection of antimicrobial resistance sequences.

Lakin Steven M SM Kuhnle Alan A Alipanahi Bahar B Noyes Noelle R NR Dean Chris C Muggli Martin M Raymond Rob R Abdo Zaid Z Prosperi Mattia M Belk Keith E KE Morley Paul S PS Boucher Christina C

Communications biology 20190806

The characterization of antimicrobial resistance genes from high-throughput sequencing data has become foundational in public health research and regulation. This requires mapping sequence reads to databases of known antimicrobial resistance genes to determine the genes present in the sample. Mapping sequence reads to known genes is traditionally accomplished using alignment. Alignment methods have high specificity but are limited in their ability to detect sequences that are divergent from the ...[more]

PMID: 31396574

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Project description:BackgroundRiboswitches are a type of noncoding RNA that regulate gene expression by switching from one structural conformation to another on ligand binding. The various classes of riboswitches discovered so far are differentiated by the ligand, which on binding induces a conformational switch. Every class of riboswitch is characterized by an aptamer domain, which provides the site for ligand binding, and an expression platform that undergoes conformational change on ligand binding. The sequence and structure of the aptamer domain is highly conserved in riboswitches belonging to the same class. We propose a method for fast and accurate identification of riboswitches using profile Hidden Markov Models (pHMM). Our method exploits the high degree of sequence conservation that characterizes the aptamer domain.ResultsOur method can detect riboswitches in genomic databases rapidly and accurately. Its sensitivity is comparable to the method based on the Covariance Model (CM). For six out of ten riboswitch classes, our method detects more than 99.5% of the candidates identified by the much slower CM method while being several hundred times faster. For three riboswitch classes, our method detects 97-99% of the candidates relative to the CM method. Our method works very well for those classes of riboswitches that are characterized by distinct and conserved sequence motifs.ConclusionRiboswitches play a crucial role in controlling the expression of several prokaryotic genes involved in metabolism and transport processes. As more and more new classes of riboswitches are being discovered, it is important to understand the patterns of their intra and inter genomic distribution. Understanding such patterns will enable us to better understand the evolutionary history of these genetic regulatory elements. However, a complete picture of the distribution pattern of riboswitches will emerge only after accurate identification of riboswitches across genomes. We believe that the riboswitch detection method developed in this paper will aid in that process. The significant advantage in terms of speed, of our pHMM-based approach over the method based on CM allows us to scan entire databases (rather than 5'UTRs only) in a relatively short period of time in order to accurately identify riboswitch candidates.

Project description:Animal movement is the mechanism connecting landscapes to fitness, and understanding variation in seasonal animal movements has benefited from the analysis and categorization of animal displacement. However, seasonal movement patterns can defy classification when movements are highly variable. Hidden Markov movement models (HMMs) are a class of latent-state models well-suited to modeling movement data. Here, we used HMMs to assess seasonal patterns of variation in the movement of pronghorn (Antilocapra americana), a species known for variable seasonal movements that challenge analytical approaches, while using a population of mule deer (Odocoileus hemionus), for whom seasonal movements are well-documented, as a comparison. We used population-level HMMs in a Bayesian framework to estimate a seasonal trend in the daily probability of transitioning between a short-distance local movement state and a long-distance movement state. The estimated seasonal patterns of movements in mule deer closely aligned with prior work based on indices of animal displacement: a short period of long-distance movements in the fall season and again in the spring, consistent with migrations to and from seasonal ranges. We found seasonal movement patterns for pronghorn were more variable, as a period of long-distance movements in the fall was followed by a winter period in which pronghorn were much more likely to further initiate and remain in a long-distance movement pattern compared with the movement patterns of mule deer. Overall, pronghorn were simply more likely to be in a long-distance movement pattern throughout the year. Hidden Markov movement models provide inference on seasonal movements similar to other methods, while providing a robust framework to understand movement patterns on shorter timescales and for more challenging movement patterns. Hidden Markov movement models can allow a rigorous assessment of the drivers of changes in movement patterns such as extreme weather events and land development, important for management and conservation.

Dataset Information

Hierarchical Hidden Markov models enable accurate and diverse detection of antimicrobial resistance sequences.

Publications

Hierarchical Hidden Markov models enable accurate and diverse detection of antimicrobial resistance sequences.

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