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Results for “Disease Susceptibility”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients

Abstract Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Disease resistance in coral is mediated by distinct adaptive and plastic gene expression profiles

Infectious diseases are an increasing threat to coral reefs, resulting in altered community structure and hindering the functional contributions of disease-susceptible species. We exposed seven reef-building coral species from the Caribbean to white plague disease and determined processes involved in (i) lesion progression, (ii) within-species gene expression plasticity, and (iii) expression-level adaptation among species that lead to differences in disease risk. Gene expression networks enriched in immune genes and cytoskeletal arrangement processes were correlated to lesion progression rates. Whether or not a coral developed a lesion was mediated by plasticity in genes involved in extracellular matrix maintenance, autophagy, and apoptosis, while resistant coral species had constitutively higher expression of intracellular protein trafficking. This study offers insight into the process involved in lesion progression and within- and between-species dynamics that lead to differences in disease risk that is evident on current Caribbean reefs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Bacterium-enabled transient gene activation by artificial transcription factors for resolving gene regulation in maize

Abstract Understanding gene regulatory networks is essential to elucidate developmental processes and environmental responses. Here, we studied regulation of a maize (Zea mays) transcription factor gene using designer transcription activator-like effectors (dTALes), which are synthetic Type III TALes of the bacterial genus Xanthomonas and serve as inducers of disease susceptibility gene transcription in host cells. The maize pathogen Xanthomonas vasicola pv. vasculorum was used to introduce 2 independent dTALes into maize cells to induced expression of the gene glossy3 (gl3), which encodes a MYB transcription factor involved in biosynthesis of cuticular wax. RNA-seq analysis of leaf samples identified, in addition to gl3, 146 genes altered in expression by the 2 dTALes. Nine of the 10 genes known to be involved in cuticular wax biosynthesis were upregulated by at least 1 of the 2 dTALes. A gene previously unknown to be associated with gl3, Zm00001d017418, which encodes aldehyde dehydrogenase, was also expressed in a dTALe-dependent manner. A chemically induced mutant and a CRISPR-Cas9 mutant of Zm00001d017418 both exhibited glossy leaf phenotypes, indicating that Zm00001d017418 is involved in biosynthesis of cuticular waxes. Bacterial protein delivery of dTALes proved to be a straightforward and practical approach for the analysis and discovery of pathway-specific genes in maize.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Differential transcriptomic alterations in nasal versus lung tissue of acrolein-exposed rats

Introduction: Acrolein is a significant component of anthropogenic and wildfire emissions, as well as cigarette smoke. Although acrolein primarily deposits in the upper respiratory tract upon inhalation, patterns of site-specific injury in nasal versus pulmonary tissues are not well characterized. This assessment is critical in the design of in vitro and in vivo studies performed for assessing health risk of irritant air pollutants. Methods: In this study, male and female Wistar-Kyoto rats were exposed nose-only to air or acrolein. Rats in the acrolein exposure group were exposed to incremental concentrations of acrolein (0, 0.1, 0.316, 1 ppm) for the first 30 min, followed by a 3.5 h exposure at 3.16 ppm. In the first cohort of male and female rats, nasal and bronchoalveolar lavage fluids were analyzed for markers of inflammation, and in a second cohort of males, nasal airway and left lung tissues were used for mRNA sequencing. Results: Protein leakage in nasal airways of acrolein-exposed rats was similar in both sexes; however, inflammatory cells and cytokine increases were more pronounced in males when compared to females. No consistent changes were noted in bronchoalveolar lavage fluid of males or females except for increases in total cells and IL-6. Acrolein-exposed male rats had 452 differentially expressed genes (DEGs) in nasal tissue versus only 95 in the lung. Pathway analysis of DEGs in the nose indicated acute phase response signaling, Nrf2-mediated oxidative stress, unfolded protein response, and other inflammatory pathways, whereas in the lung, xenobiotic metabolism pathways were changed. Genes associated with glucocorticoid and GPCR signaling were also changed in the nose but not in the lung. Discussion: These data provide insights into inhaled acrolein-mediated sex-specific injury/inflammation in the nasal and pulmonary airways. The transcriptional response in the nose reflects acrolein-induced acute oxidative and cytokine signaling changes, which might have implications for upper airway inflammatory disease susceptibility.

Alewel, Devin I.↗
DOE OSTI2025

scRNA seq of an F1 cross of Marek’s disease resistant and susceptible chickens identifies allele specific expression signatures enriched in transcription modulators

Abstract Marek’s disease (MD), a T cell lymphoma disease in chickens, is caused by the Marek’s disease virus (MDV) found ubiquitously in the poultry industry. Genetically resistant Line 6 3 (L6) and susceptible Line 7 2 (L7) chickens have been instrumental to research on avian immune system response to MDV infection. In this study we characterized molecular signatures unique to splenic immune cell types across different genetic backgrounds 6 days after infection. Using three populations, L6, L7, and an F1 cross between L6xL7, we evaluated the immune cell transcriptome of responding cell types using single cell RNA sequencing. Several MDV genes were found expressed mainly in cytotoxic T cells while ICP4 and MEQ MDV genes were expressed across infected cell types. Using the F1 we quantified allele specific expression (ASE) of biallelic SNPs and found biased expression of parental alleles specific to immune cell subtypes. We identified 22 SNPs with ASE in response to MDV infection mapped to gene rich regions surrounding 59 genes of critical importance for chromatin remodeling and transcriptional regulation. Histone deacetylase genes (HDAC1 and HDAC8) had increased expression of L6 alleles, while small nuclear RNA genes (SNORA68 and SNORA72) expressed higher levels of L7 alleles with infection in T cell subsets. SNPs with ASE also mapped genes important for an adequate immune response including GNLY (cytotoxic activity) and PDIA3 (component of MHC class I peptide loading complex), and genes known to promote viral replication (MCM5 and EIF3M). These results show that functional variants associated with susceptibility to MD may have a bigger impact in subsets of immune cell types, and by characterizing the transcriptomes of these subtypes we can unravel molecular signatures specific to MD genomic resistance.

Science & Technology - Other Topics↗
DOE OSTI2022

Proteomics reveals pathways linked to septoria canker resistance and susceptibility in Populus trichocarpa

A major threat to forest ecosystems and plantation forestry is the introduction of a non-native pathogen. Among non-domesticated populations with relatively high levels of genetic diversity, a measurable range of susceptibility to resistance can be expected. Identifying genetic determinants of resistant and susceptible individuals can inform the development of new strategies to engineer disease resistance. Here we describe pathogen-induced changes in the proteome of Populus trichocarpa stem tissue in response to Sphaerulia musiva (Septoria canker). This hemibiotrophic fungal pathogen causes stem canker disease in susceptible poplar genotypes. Proteomics analyses were performed on stem tissue harvested across 0-, 12-, 24- and 48-h post-inoculation with Septoria from three genotypes including one resistant (BESC-22) and two susceptible [BESC-801; Nisqually-1 (NQ-1)]. In total, 11,897 Populus proteins at FDR <0.01 were identified across all time points and genotypes. Analysis of protein abundances between genotypes revealed that the resistant poplar genotype (BESC-22) mounts a rapid and sustained defense response involving pattern recognition receptors, calcium signaling proteins, SAR inducers, transcriptional regulators, resistance proteins, and proteins involved with the hypersensitive response. One susceptible genotype (BESC-801) had a downregulated and delayed defense response whereas the second susceptible genotype (NQ-1) lacked a distinct pattern. Overall, the proteome-wide and protein-specific trends suggest that responses to the Septoria canker infection are genotype-specific for the naïve host, Populus trichocarpa .

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Introgressions of novel diseases resistance genes from Miscanthus into energycane

Sugarcane (Saccharum) is among the world’s leading bioenergy crops. However, modern sugarcane cultivars are derived from a relatively small set of founder genotypes, which has contributed to cultivar susceptibility to diseases. Miscanthus is a close relative of sugarcane that is genetically diverse and a potential source of genes for improving sugarcane. We found that Miscanthus is a source of resistance to four major diseases of sugarcane and we crossed these disease-resistance genes into a predominantly sugarcane genetic background (BC1 generation). Additionally, we found that Miscanthus could also confer genes for chilling-tolerant photosynthesis to sugarcane, which would be highly advantageous for production of energycane in subtropical environments, like the southern coastal plain of the US. Using advanced modeling techniques, we found that standard marker-assisted selection could be effective for breeding resistance conferred by a small number of genes each with large effect (i.e. vertical resistance), but to breed for many genes each of small effect (i.e. horizontal resistance), genomic selection would be the better strategy. Lastly, we learned that Miscanthus can be induced to flower sooner by giving the plants short days (long nights) but that the ideal day length for a given accession depends on its adaptation to its latitude of origin, with tropical accessions requiring shorter days to flower than accessions from high latitudes. This information will facilitate plant breeders’ ability to make crosses between Miscanthus and sugarcane, and enable greater use of Miscanthus as a genetic resource to improve sugarcane.

09 BIOMASS FUELS↗
DOE OSTI2023

Latent Dirichlet Allocation modeling of environmental microbiomes

Interactions between stressed organisms and their microbiome environments may provide new routes for understanding and controlling biological systems. However, microbiomes are a form of high-dimensional data, with thousands of taxa present in any given sample, which makes untangling the interaction between an organism and its microbial environment a challenge. Here we apply Latent Dirichlet Allocation (LDA), a technique for language modeling, which decomposes the microbial communities into a set of topics (non-mutually-exclusive sub-communities) that compactly represent the distribution of full communities. LDA provides a lens into the microbiome at broad and fine-grained taxonomic levels, which we show on two datasets. In the first dataset, from the literature, we show how LDA topics succinctly recapitulate many results from a previous study on diseased coral species. We then apply LDA to a new dataset of maize soil microbiomes under drought, and find a large number of significant associations between the microbiome topics and plant traits as well as associations between the microbiome and the experimental factors, e.g. watering level. This yields new information on the plant-microbial interactions in maize and shows that LDA technique is useful for studying the coupling between microbiomes and stressed organisms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

A cross-sectional study of the nasal and fecal microbiota of sows from different health status within six commercial swine farms

Cull sows are a unique population on swine farms, often representing poor producing or compromised animals, and even though recent studies have reported that the microbiome is associated with susceptibility to diseases, the microbiome of the cull sow population has not been explored. The main objective of this study was to investigate whether there were differences in fecal and upper respiratory tract microbiota composition for groups of sows of different health status (healthy, cull, and compromised/ clinical sows) and from different farms (1 to 6). Six swine farms were visited once. Thirty individual fecal samples and nasal swabs were obtained at each farm and pooled by five across health status and farm. Samples underwent 16S rRNA gene amplicon sequencing and nasal and fecal microbiota were analyzed using QIIME2 v.2021.4. Overall, the diversity of the nasal microbiota was lower than the fecal microbiota (p < 0.01). No significant differences were found in fecal or nasal alpha diversity by sow’s health status or by farm. Furthermore, there were significant differences in nasal microbial composition by farm and health status (PERMANOVA, p < 0.05), and in fecal microbiota by farm (PERMANOVA, p < 0.05), but not by health status. Lastly, at the L7 level, there was one differentially abundant taxa across farms for each nasal and fecal pooled samples. This study provided baseline information for nasal and fecal microbiota of sows under field conditions, and results suggest that farm of origin can affect microbial diversity and composition. Furthermore, sow’s health status may have an impact on the nasal microbiota composition.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Large-scale Nonlinear Approaches for Inference of Reporting Dynamics and Unobserved SARS-CoV-2 Infections

This work focuses on estimation of unknown states and parameters in a discrete-time, stochastic, SEIR model using reported case counts and mortality data. An SEIR model is based on classifying individuals with respect to their status in regards to the progression of the disease, where S is the number individuals who remain susceptible to the disease, E is the number of individuals who have been exposed to the disease but not yet infectious, I is the number of individuals who are currently infectious, and R is the number of recovered individuals. For convenience, we include in our notation the number of infections or transmissions, T, that represents the number of individuals transitioning from compartment S to compartment E over a particular interval. Similarly, we use C to represent the number of reported cases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Warning Signs of Potential Black Swan Outbreaks in Infectious Disease

Black swan events in infectious disease describe rare but devastatingly large outbreaks. While experts are skeptical that such events are predictable, it might be possible to identify the warning signs of a black swan event. Specifically, following the initiation of an outbreak, key differentiating features could serve as alerts. Such features could be derived from meta-analyses of large outbreaks for multiple infectious diseases. We hypothesized there may be common features among the pathogen, environment, and host epidemiological triad that characterize an infectious disease black swan event. Using Los Alamos National Laboratory’s tool, Analytics for Investigation of Disease Outbreaks, we investigated historical disease outbreak information and anomalous events for several infectious diseases. By studying 32 different infectious diseases and global outbreaks, we observed that in the past 20–30 years, there have been potential black swan events in the majority of infectious diseases analyzed. Importantly, these potential black swan events cannot be attributed to the first introduction of the disease to a susceptible host population. This paper describes our observations and perspectives and illustrates the value of broad analysis of data across the infectious disease realm, providing insights that may not be possible when we focus on singular infectious agents or diseases. Data analytics could be developed to warn health authorities at the beginning of an outbreak of an impending black swan event. Such tools could complement traditional epidemiological modeling to help forecast future large outbreaks and facilitate timely warning and effective, targeted resource allocation for mitigation efforts.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Single-cell profiling of Arabidopsis leaves to Pseudomonas syringae infection

Plant response to pathogen infection varies within a leaf, yet this heterogeneity is not well resolved. We expose Arabidopsis to Pseudomonas syringae or mock treatment and profile >11,000 individual cells using single-cell RNA sequencing. Integrative analysis of cell populations from both treatments identifies distinct pathogen-responsive cell clusters exhibiting transcriptional responses ranging from immunity to susceptibility. Pseudotime analyses through pathogen infection reveals a continuum of disease progression from an immune to a susceptible state. Confocal imaging of promoter-reporter lines for transcripts enriched in immune cell clusters shows expression surrounding substomatal cavities colonized or in close proximity to bacterial colonies, suggesting that cells within immune clusters represent sites of early pathogen invasion. Susceptibility clusters exhibit more general localization and are highly induced at later stages of infection. Overall, our work shows cellular heterogeneity within an infected leaf and provides insight into plant differential response to infection at a single-cell level.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Rapid, antibiotic incubation-free determination of tuberculosis drug resistance using machine learning and Raman spectroscopy

Tuberculosis (TB) is the world’s deadliest infectious disease, with over 1.5 million deaths and 10 million new cases reported anually. The causative organism Mycobacterium tuberculosis (Mtb) can take nearly 40 d to culture, a required step to determine the pathogen’s antibiotic susceptibility. Both rapid identification and rapid antibiotic susceptibility testing of Mtb are essential for effective patient treatment and combating antimicrobial resistance. Here, we demonstrate a rapid, culture-free, and antibiotic incubation-free drug susceptibility test for TB using Raman spectroscopy and machine learning. We collect few-to-single-cell Raman spectra from over 25,000 cells of the Mtb complex strain Bacillus Calmette-Guérin (BCG) resistant to one of the four mainstay anti-TB drugs, isoniazid, rifampicin, moxifloxacin, and amikacin, as well as a pan-susceptible wildtype strain. By training a neural network on this data, we classify the antibiotic resistance profile of each strain, both on dried samples and on patient sputum samples. On dried samples, we achieve >98% resistant versus susceptible classification accuracy across all five BCG strains. In patient sputum samples, we achieve ~79% average classification accuracy. We develop a feature recognition algorithm in order to verify that our machine learning model is using biologically relevant spectral features to assess the resistance profiles of our mycobacterial strains. Finally, we demonstrate how this approach can be deployed in resource-limited settings by developing a low-cost, portable Raman microscope that costs <$5,000. We show how this instrument and our machine learning model enable combined microscopy and spectroscopy for accurate few-to-single-cell drug susceptibility testing of BCG.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Experimental Senecavirus A Infection of Bovine Cell Lines and Colostrum-Deprived Calves

Senecavirus A (SVA) is a causative agent for vesicular disease in swine, which is clinically indistinguishable from other vesicular diseases of swine including foot-and-mouth disease (FMD). Recently, it was reported that buffalo in Guangdong, China were experiencing clinical symptoms similar to FMD including mouth ulcers and lameness tested positive for SVA. The objective of this study was to determine the susceptibility of cattle (Bos taurus) to SVA infection. Initial in vitro work using the PrimeFlow assay demonstrated that bovine cell lines and peripheral blood mononuclear cells from cattle were susceptible to SVA infection. Subsequently, six colostrum-deprived Holstein calves were challenged with SVA intranasally. No vesicular lesions were observed after challenge. Serum, oral, nasal, and rectal swabs tested for SVA nucleic acid did not support significant viral replication and there was no evidence of seroconversion. Therefore, demonstrating cattle from this study were not susceptible to experimental SVA infection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Biochemical basis for the formation of organ-specific volatile blends in mint

Above-ground material of members of the mint family is commercially distilled to extract essential oils, which are then formulated into a myriad of consumer products. Most of the research aimed at characterizing the processes involved in the formation of terpenoid oil constituents has focused on leaves. We now demonstrate, by investigating three mint species, peppermint ( Mentha ˣ piperita L.), spearmint ( Mentha spicata L.) and horsemint ( Mentha longifolia (L.) Huds.; accessions CMEN 585 and CMEN 584), that other organs – namely stems, rhizomes and roots – also emit volatiles and that the terpenoid volatile composition of these organs can vary substantially from that of leaves, supporting the notion that substantial, currently underappreciated, chemical diversity exists. Differences in volatile quantities released by plants whose roots had been dipped in a Verticillium dahliae -spore suspension (experimental) or dipped in water (controls) were evident: increases of some volatiles in the root headspace of mint species that are susceptible to Verticillium wilt disease (peppermint and M. longifolia CMEN 584) were detected, while the quantities of certain volatiles decreased in rhizomes of species that show resistance to the disease (spearmint and M. longifolia CMEN 585). To address the genetic and biochemical basis underlying chemical diversity, we took advantage of the newly sequenced M. longifolia CMEN 585 genome to identify candidate genes putatively coding for monoterpene synthases (MTSs), the enzymes that catalyze the first committed step in the biosynthesis of monoterpenoid volatiles. The functions of these genes were established by heterologous expression in Escherichia coli , purification of the corresponding recombinant proteins, and enzyme assays, thereby establishing the existence of MTSs with activities to convert a common substrate, geranyl diphosphate, to (+)-α-terpineol, 1,8-cineole, γ-terpinene, and (–)-bornyl diphosphate, but were not active with other potential substrates. In conjunction with previously described MTSs that catalyze the formation of (–)-β-pinene and (–)-limonene, the product profiles of the MTSs identified here can explain the generation of all major monoterpene skeletons represented in the volatiles released by different mint organs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Acute Ozone-Induced Transcriptional Changes in Markers of Oxidative Stress and Glucocorticoid Signaling in the Rat Hippocampus and Hypothalamus Are Sex-Specific

Exposure to a prototypic air pollutant ozone (O 3 ) has been associated with the activation of neuroendocrine stress response along with neural changes in oxidative stress (OS), inflammation, and Alzheimer’s disease-like pathologies in susceptible animal models. We hypothesized that neural oxidative and transcriptional changes induced by O 3 in stress responsive regions are sex-dependent. Male and female adult Long–Evans rats were exposed to filtered air or O 3 for two consecutive days (0.8 ppm, 4 h/day) and brain regions were flash-frozen. Activities of cerebellar OS parameters and mitochondrial complex I, II, and IV enzymes were assessed to confirm prior findings. We assessed transcriptional changes in hypothalamus (HYP) and hippocampus (HIP) for markers of OS, microglial activity and glucocorticoid signaling using qPCR. Although there were no O 3 or sex-related differences in the cerebellar activities of OS and mitochondrial enzymes, the levels of protein carbonyls and complex II activities were higher in females regardless of O 3 . There were no statistical differences in baseline expression of genes related to OS (Cat, Dhcr24, Foxm1, Gpx1, Gss, Nfe2l2, Sod1) except for lower HYP Sod1 expression in air-exposed females than males, and higher HIP Gss expression in O 3 -exposed females relative to matched males. Microglial marker Aif1 expression was higher in O 3 -exposed females relative to males; O 3 inhibited Itgam only in males. The expression of Bdnf in HIP and HYP was inhibited by O 3 in both sexes. Genes related to glucocorticoid signaling (Fkbp4, Fkbp5, Hsp90aa1, Hspa4, nr3c1, nr3c2) showed sex-specific effects due to O 3 exposure. Baseline expression of HIP Fkbp4 was higher in females relative to males. O 3 inhibited Nr3c1 in female HIP and male HYP, but Nr3c2 was inhibited in male HYP. Fkbp4 expression was higher in O 3 -exposed females when compared to matched males, whereas Fkbp5 was expressed at higher levels in both brain regions of males and females. These results indicate that sex-specific brain region responses to O 3 might, in part, be caused by OS and regulation of glucocorticoid signaling.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Bark morphological and chemical features are differentially correlated with disease resistance and yield in hybrid poplar taxa

In the southeastern United States, the establishment of short-rotation intensively cultured plantations of hybrid poplar has been hindered by its susceptibility to stem cankers. We evaluated the tradeoffs between biomass yield and disease tolerance in hybrid poplar genotypes belonging to P. deltoides × P. maximowiczii (DM), P. deltoides × P. nigra (DN), P. trichocarpa × P. maximowiczii (TM), and P. deltoides × P. deltoides (DD) taxa. We hypothesized that canker resistant genotypes will have thicker bark but bark thickness and biomass yield will be negatively correlated. After two growing seasons, the DD genotypes developed thicker bark compared to the genotypes of other taxa and bark thickness was not correlated with biomass yield in the DD genotypes (R 2 = 0.002). However, in the TM, DM, and DN genotypes, bark thickness was negatively correlated with biomass yield (R 2 = 0.33–0.77). Disease incidence studies revealed that the DM genotypes were most susceptible to canker whereas no disease was detected in DD genotypes. Furthermore, bark analysis conducted by Fourier transform infrared spectroscopy coupled with multivariate analysis showed that that DD genotypes to be chemically separate from the three hybrid genotypes and that bark chemistry was correlated with canker disease incidence. Taken together, these results reveal that it is possible to generate hybrid poplar genotypes with thicker bark, disease resistance, and higher biomass yields. This insight should guide further efforts to develop genetically improved hybrid poplar genotypes, both in terms of biomass yield and disease tolerance, for cultivation in the southeastern United States. Hybrid poplar cultivation in southeastern United States is hindered by its susceptibility to stem cankers. We evaluated tradeoffs between yield and canker disease resistance in various hybrid poplar genotypes. After two growing seasons, the DD genotypes showed disease resistance and developed thicker bark that was chemically distinct from the other genotypes. Bark thickness was not correlated with yield in the DD genotypes but was negatively correlated with yield in the other genotypes. These results will guide the development of hybrid poplar genotypes that are both disease resistant and high yielding for cultivation in the southeastern United States.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

An accurate and interpretable model for antimicrobial resistance in pathogenic Escherichia coli from livestock and companion animal species

Understanding the microbial genomic contributors to antimicrobial resistance (AMR) is essential for early detection of emerging AMR infections, a pressing global health threat in human and veterinary medicine. Here we used whole genome sequencing and antibiotic susceptibility test data from 980 disease causing Escherichia coli isolated from companion and farm animals to model AMR genotypes and phenotypes for 24 antibiotics. We determined the strength of genotype-to-phenotype relationships for 197 AMR genes with elastic net logistic regression. Model predictors were designed to evaluate different potential modes of AMR genotype translation into resistance phenotypes. Our results show a model that considers the presence of individual AMR genes and total number of AMR genes present from a set of genes known to confer resistance was able to accurately predict isolate resistance on average (mean F 1 score = 98.0%, SD = 2.3%, mean accuracy = 98.2%, SD = 2.7%). However, fitted models sometimes varied for antibiotics in the same class and for the same antibiotic across animal hosts, suggesting heterogeneity in the genetic determinants of AMR resistance. We conclude that an interpretable AMR prediction model can be used to accurately predict resistance phenotypes across multiple host species and reveal testable hypotheses about how the mechanism of resistance may vary across antibiotics within the same class and across animal hosts for the same antibiotic.

Chung, Henri C.↗