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Ternus, K.

Publications and source records attributed to Ternus, K..

4 recordsLinked to original sources

Inter-tool analysis of a NIST dataset for assessing baseline nucleic acid sequence screening

Nucleic acid synthesis is a dual-use technology that can benefit fields such as biology, medicine, and information storage. However, synthetic nucleic acids could also potentially be used negligently and ultimately cause harm, or be used with malicious intent to cause harm. Thus, this technology needs to be appropriately safeguarded. Sequence screening is one component of a biosecurity protocol for preventing such harm and consists of differentiating Sequences of Concern (SOCs) from benign sequences that are not associated with pathogenicity or toxicity. There exist many fit-for-purpose tools that have been developed for DNA synthesis sequence screening. However, questions remain regarding their performance with respect to consistency of screening. To aid in determining if screening tools are harmonized in regard to baseline sequence screening, NIST constructed a test dataset based on current screening recommendations. NIST then sent blinded datasets to sequence screening tool developers for testing. Overall, there was a general agreement between the tools and NIST assignments of the sequences and all tools had a baseline performance of greater than 95% sensitivity and 97% accuracy. Disagreement on specific sequences largely arose from single tools and could be traced to differences in defining a SOC and/or methodological differences in screening algorithms.

bioinformatics↗

Predicting characterization of microbiome taxonomy from imaging using machine learning approaches

AO_SCPLOWBSTRACTC_SCPLOWFor this study, a total of 47 mock human skin microbiome communities were created using microorganisms collected from human donors and grown in vitro for between eight and 32 days. Each mock community sample was split. Ten mL of each sample was used to determine the taxonomy of the community, using metatranscriptomics and Kraken2 to provide population-level taxonomic information; five mL of each sample was used for imaging. The resulting micrographs served as the basis for establishing a new analysis pipeline that sequentially used two different methods for machine learning and one statistical technique: (1) confocal microscopy images were segmented into individual cells using the generalist, deep learning, publicly available machine learning model Cellpose; (2) continuous probability density functions describing the joint distribution of the cell area and eccentricity were found using algorithms expressing the statistical technique of kernel density estimation; (3) these probability density functions were used as input for convolutional neural networks, that were trained to predict both the taxonomic diversity and the most common bacterial class, independently of metatranscriptomics. Specifically, models were made to predict the Shannon index (a quantitative measure of taxonomic diversity) and to predict the most common bacterial class, for each micrograph. Measured Shannon indices (based on metatranscriptomics) ranged from nearly 0 to 1.4. The model predictions of Shannon indices had a mean squared error of 0.0321 +/- 0.0035. The model predictions of the most common taxonomic class of bacteria had an accuracy of 94.0% +/- 0.7%. IO_SCPLOWMPORTANCEC_SCPLOWTaxonomic diversity is a useful metric for describing microbial communities and can be used as a measure of ecosystems health, resilience, and biological interactions. Characterization of microbial community diversity also has diagnostic applications. For the human skin microbiome in particular, microbial diversity directly impacts skin health, including resilience against pathogens and regulation of immune responses. Currently, microbial diversity can be determined either using traditional staining methods that are limited to pure cultures or using sequencing methods that require high investment in cost, time, and expertise. In this study, we demonstrate an innovative method that employs microscopy images of bacterial communities and machine learning to predict taxonomic diversity and the dominant bacterial classes of bacterial communities. The underlying framework of the pipeline for taxonomy prediction has the potential to be adapted and extended to other organisms and microbiomes and to make taxonomic analyses less expensive and more feasible in low-resource settings.

microbiology↗

SeqScreen: Accurate and Sensitive Functional Screening of Pathogenic Sequences via Ensemble Learning

The COVID-19 pandemic has emphasized the importance of detecting known and emerging pathogens from clinical and environmental samples. However, robust characterization of pathogenic sequences remains an open challenge. To this end, we developed SeqScreen, which can accurately characterize short nucleotide sequences using taxonomic and functional labels, and a customized set of curated Functions of Sequences of Concern (FunSoCs) specific to microbial pathogenesis. We show our ensemble machine learning model can label protein-coding sequences with FunSoCs with high recall and precision. SeqScreen is a step towards a novel paradigm of functionally informed pathogen characterization and is available for download at: www.gitlab.com/treangenlab/seqscreen

bioinformatics↗

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↗