Multi-platform omics analysis of Nipah virus infection reveals viral glycoprotein modulation of mitochondria
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59 BASIC BIOLOGICAL SCIENCES↗
Engineering topics
Oxford, Kristie L.
Publications and source records attributed to Oxford, Kristie L..
Insights from a workplace SARS-CoV-2 specimen collection program, with genomes placed into global sequence phylogeny
In 2020, the Department of Energy established the National Virtual Biotechnology Laboratory (NVBL) to address key challenges associated with COVID-19. As part of that effort, Pacific Northwest National Laboratory (PNNL) established a capability to collect and analyze specimens from employees who self-reported symptoms consistent with the disease. During the spring and fall of 2021, 688 specimens were screened for SARS-CoV-2, with 64 (9.3%) testing positive using reverse-transcriptase quantitative PCR (RT-qPCR). Of these, 36 samples were released for research. All 36 positive samples released for research were sequenced and genotyped. Here, the relationship between patient age and viral load as measured by Ct values was measured and determined to be only weakly significant. Consensus sequences for each sample were placed into a global phylogeny and transmission dynamics were investigated, revealing that the closest relative for many samples was from outside of Washington state, indicating mixing of viral pools within geographic regions.
59 BASIC BIOLOGICAL SCIENCES↗
COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms
We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
59 BASIC BIOLOGICAL SCIENCES↗
Leveraging Structured Biological Knowledge for Counterfactual Inference: A Case Study of Viral Pathogenesis
Counterfactual inference is a useful tool for comparing outcomes of interventions on complex systems. It requires us to represent the system in form of a structural causal model, complete with a causal diagram, probabilistic assumptions on exogenous variables, and functional assignments. Specifying such models can be extremely difficult in practice. The process requires substantial domain expertise, and does not scale easily to large systems, multiple systems, or novel system modifications. At the same time, many application domains, such as molecular biology, are rich in structured causal knowledge that is qualitative in nature. This manuscript proposes a general approach for querying a causal knowledge graph with a causal question and converting the qualitative result into a quantitative structural causal model that can learn from data to answer the question. Here, we demonstrate the feasibility, accuracy and versatility of this approach using two case studies in systems biology. The first demonstrates the appropriateness of the underlying assumptions and the accuracy of the results. The second demonstrates the versatility of the approach by querying a knowledge base for the molecular determinants of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm and performing counterfactual inference to predict the causal effect of medical countermeasures for severely ill COVID-19 patients.
60 APPLIED LIFE SCIENCES↗
Evaluation of Three RNA Extraction Kits with a 2019-nCoV Assay
The following characteristics of three RNA extraction kits (Norgen Biotek Total RNA Purification Kit, #17200; Bioneer AccuPrep Viral RNA Extraction Kit, #K-3033; and Promega Maxwell HT Viral TNA Kit, #AX2340) were evaluated: Limits of detection for quantitative synthetic RNA using the Centers for Disease Control and Prevention’s (CDC) 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel and the Applied Biosystems 7500 Fast Dx system; Limits of detection for positive clinical specimen using the Centers for Disease Control and Prevention’s (CDC) 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel and the Applied Biosystems 7500 Fast Dx system; Ability of the lysis buffers in each kit to inactivate the virus as measured by a cell-based infectivity assay.
60 APPLIED LIFE SCIENCES↗