Search bioRxiv⌕ Search

Biology subjects

Treangen, T. J.

Publications and source records attributed to Treangen, T. J..

23 records · Page 2Linked to original sources

Hidden genomic diversity of SARS-CoV-2: implications for qRT-PCR diagnostics and transmission

The COVID-19 pandemic has sparked an urgent need to uncover the underlying biology of this devastating disease. Though RNA viruses mutate more rapidly than DNA viruses, there are a relatively small number of single nucleotide polymorphisms (SNPs) that differentiate the main SARS-CoV-2 clades that have spread throughout the world. In this study, we investigated over 7,000 SARS-CoV-2 datasets to unveil both intrahost and interhost diversity. Our intrahost and interhost diversity analyses yielded three major observations. First, the mutational profile of SARS-CoV-2 highlights iSNV and SNP similarity, albeit with high variability in C>T changes. Second, iSNV and SNP patterns in SARS-CoV-2 are more similar to MERS-CoV than SARS-CoV-1. Third, a significant fraction of small indels fuel the genetic diversity of SARS-CoV-2. Altogether, our findings provide insight into SARS-CoV-2 genomic diversity, inform the design of detection tests, and highlight the potential of iSNVs for tracking the transmission of SARS-CoV-2.

genomics↗

KOMB: Taxonomy-oblivious Characterization of Metagenome Dynamics via K-core Decomposition

Characterizing metagenomic samples via kmer-based, database-dependent taxonomic classification methods has provided crucial insight into underlying host-associated microbiome dynamics. However, novel approaches are needed that are able to track microbial community dynamics within metagenomes to elucidate genome flux in response to perturbations and disease states. Here we describe KOMB, a novel approach for tracking homologous regions within microbiomes. KOMB utilizes K-core graph decomposition on metagenome assembly graphs to identify repetitive and homologous regions to varying degrees of resolution. K-core performs a hierarchical decomposition which partitions the graph into shells containing nodes having degree at least K, called K-shells, yielding O(V + E) complexity compared to exact betweenness centrality complexity of O(V E) found in prior related approaches. We show through rigorous validation on simulated, synthetic, and real metagenomic datasets that KOMB accurately recovers and profiles repetitive and homologous genomic regions across organisms in the sample. KOMB can also identify functionally-rich regions in Human Microbiome Project (HMP) datasets, and can be used to analyze longitudinal data and identify pivotal taxa in fecal microbiota transplantation (FMT) samples. In summary, KOMB represents a novel approach to microbiome characterization that can efficiently identify sequences of interest in metagenomes.

bioinformatics↗

Diversified RACE Sampling on Data Streams Applied to Metagenomic Sequence Analysis

The rise of whole-genome shotgun sequencing (WGS) has enabled numerous breakthroughs in large-scale comparative genomics research. However, the size of genomic datasets has grown exponentially over the last few years, leading to new challenges for traditional streaming algorithms. Modern petabyte-sized genomic datasets are difficult to process because they are delivered by high-throughput data streams and are difficult to store. As a result, many traditional streaming problems are becoming increasingly relevant. One such problem is the task of constructing a maximally diverse sample over a data stream. In this regime, complex sampling procedures are not possible due to the overwhelming data generation rate. In theory, the best diversity sampling methods are based on a simple greedy algorithm that compares the current sequence with a large pool of sampled sequences and decides whether to accept or reject the sequence. While these methods are elegant and optimal, they are largely confined to the theoretical realm because the greedy procedure is too slow in practice. While there are many methods to identify common elements in data streams efficiently, fast and memory-efficient diversity sampling remains a challenging and fundamental data streaming problem with few satisfactory solutions. In this work, we bridge the gap with RACE sampling, an online algorithm for diversified sampling. Unlike random sampling, which samples uniformly, RACE selectively accepts samples from streams that lead to higher sequence diversity. At the same time, RACE is as computationally efficient as random sampling and avoids pairwise similarity comparisons between sequences. At the heart of RACE lies an efficient lookup array constructed using locality-sensitive hashing (LSH). Our theory indicates that an accept/reject procedure based on LSH lookups is sufficient to obtain a highly diverse subsample. We provide rigorous theoretical guarantees for well-known biodiversity indices and show that RACE can nearly double the Shannon and Simpson indices of a genetic sample in practice, all while using the same resources as random sampling. We also compare RACE against Diginorm and coreset-based diversity sampling methods and find that RACE is faster and more memory efficient. Our algorithm is straightforward to implement, easy to parallelize, and fast enough to keep pace with the overwhelming data generation rates. We expect that as DNA sequence data streams become more mainstream and faster, RACE will become an essential component for many applications.1

bioinformatics↗

RefSeq database growth influences the accuracy of k-mer-based species identification

Accurate species-level taxonomic classification and profiling of complex microbial communities remains a challenge due to homologous regions shared among closely related species and a sparse representation of non-human associated microbes in the database. Although the database undoubtedly has a strong influence on the sensitivity of taxonomic classifiers and profilers, to date, no study has carefully explored this topic on historical RefSeq releases and explored its impact on accuracy. In this study, we examined the influence of the database, over time, on k-mer based sequence classification and profiling. We present three major findings: (i) database growth over time resulted in more classified reads, but fewer species-level classifications and more species-level misclassifications; (ii) Bayesian re-estimation of abundance helped to recover species-level classifications when the exact target strain was present; and (iii) Bayesian reestimation struggled when the database lacked the target strain, resulting in a notable decrease in accuracy. In summary, our findings suggest that the growth of RefSeq over time has strongly influenced the accuracy of k-mer based classification and profiling methods, resulting in different classification results depending on the particular database used. These results suggest a need for new algorithms specially adapted for large genome collections and better measures of classification uncertainty.

bioinformatics↗

MetaCompass: Reference-guided Assembly of Metagenomes

Metagenomic studies have primarily relied on de novo approaches for reconstructing genes and genomes from microbial mixtures. While database driven approaches have been employed in certain analyses, they have not been used in the assembly of metagenomes. Here we describe the first effective approach for reference-guided metagenomic assembly of low-abundance bacterial genomes that can complement and improve upon de novo metagenomic assembly methods. When combined with de novo assembly approaches, we show that MetaCompass can generate more complete assemblies than can be obtained by de novo assembly alone, and improve on assemblies from the Human Microbiome Project (over 2,000 samples).

bioinformatics↗