Communicating COVID-19 exposure risk with an interactive website counteracts risk misestimation.

During the COVID-19 pandemic, individuals depended on risk information to make decisions about everyday behaviors and public policy. Here, we assessed whether an interactive website influenced individuals' risk tolerance to support public health goals. We collected data from 11,169 unique users who engaged with the online COVID-19 Event Risk Tool (https://covid19risk.biosci.gatech.edu/) between 9/22/21 and 1/22/22. The website featured interactive elements, including a dynamic risk map, survey questions, and a risk quiz with accuracy feedback. After learning about the risk of COVID-19 exposure, participants reported being less willing to participate in events that could spread COVID-19, especially for high-risk large events. We also uncovered a bias in risk estimation: Participants tended to overestimate the risk of small events but underestimate the risk of large events. Importantly, even participants who voluntarily sought information about COVID risks tended to misestimate exposure risk, demonstrating the need for intervention. Participants from liberal-leaning counties were more likely to use the website tools and more responsive to feedback about risk misestimation, indicating that political partisanship influences how individuals seek and engage with COVID-19 information. Lastly, we explored temporal dynamics and found that user engagement and risk estimation fluctuated over the course of the Omicron variant outbreak. Overall, we report an effective large-scale method for communicating viral exposure risk; our findings are relevant to broader research on risk communication, epidemiological modeling, and risky decision-making.

Genomic analysis of Chlamydia psittaci from a multistate zoonotic outbreak in two chicken processing plants.

Four Chlamydia psittaci isolates were recovered from clinical specimens from ill workers during a multistate outbreak at two chicken processing plants. Whole genome sequencing analyses revealed high similarity to C. psittaci genotype D. The isolates differed from each other by only two single nucleotide polymorphisms, indicating a common source.

Multiplex Real-time PCR Assay for the Detection of all Chlamydia Species and Simultaneous Differentiation of C. psittaci and C. pneumoniae in Human Clinical Specimens.

We developed and assessed the performance of a new multiplex real-time PCR assay for the detection of all Chlamydia species and simultaneous differentiation of Chlamydia psittaci and Chlamydia pneumoniae-two important human respiratory pathogens-in human clinical specimens. Next-generation sequencing was used to identify unique targets to design real-time PCR assays targeting all Chlamydia species, C. psittaci, and C. pneumoniae. To validate the assay, we used a panel of 49 culture isolates comprising seven C. psittaci genotypes, eight C. pneumoniae isolates, seven other Chlamydia species, and 22 near-neighbor bacterial and viral isolates, along with 22 specimens from external quality assessment (EQA) panels and 34 nasopharyngeal and oropharyngeal swabs and cerebrospinal fluid, stool, and sputum specimens previously identified as positive or negative for C. psittaci or C. pneumoniae. The assays were 100% specific, with limits of detection of 7.64- 9.02 fg/µL. The assay results matched with historical assay results for all specimens, except for one owing to the increased sensitivity of the new C. psittaci assay; the results of the EQA specimens were 100% accurate. This assay may improve the timely and accurate clinical diagnosis of Chlamydia infections and provide a greater understanding of the burden of disease caused by these agents.

Mutations in SORL1 and MTHFDL1 possibly contribute to the development of Alzheimer's disease in a multigenerational Colombian Family.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 50 million people worldwide in 2020 and this number will triple to 152 million by 2050. Much of the increase will be in developing countries like Colombia. In familial forms, highly penetrant mutations have been identified in three genes, APP, PSEN1, and PSEN2, supporting a role for amyloid-ß peptide. In sporadic forms, more than 30 risk genes involved in the lipid metabolism, the immune system, and synaptic functioning mechanisms. We used whole-exome sequencing (WES) to evaluate a family of 97 members, spanning three generations, with a familiar AD, and without mutations in APP, PSEN1, or PSEN2. We sequenced two affected and one unaffected member with the aim of identifying genetic variants that could explain the presence of the disease in the family and the candidate variants were validated in eleven members. We also built a structural model to try to determine the effect on protein function. WES analysis identified two rare variants in SORL1 and MTHFD1L genes segregating in the family with other potential risk variants in APOE, ABCA7, and CHAT, suggesting an oligogenic inheritance. Additionally, the structural 3D models of SORL1 and MTHFD1L variants shows that these variants produce polarity changes that favor hydrophobic interactions, resulting in local structural changes that could affect the protein function and may contribute to the development of the disease in this family.

The Impact of Ethnicity and Genetic Ancestry on Disease Prevalence and Risk in Colombia.

Currently, the vast majority of genomic research cohorts are made up of participants with European ancestry. Genomic medicine will only reach its full potential when genomic studies become more broadly representative of global populations. We are working to support the establishment of genomic medicine in developing countries in Latin America via studies of ethnically and ancestrally diverse Colombian populations. The goal of this study was to analyze the effect of ethnicity and genetic ancestry on observed disease prevalence and predicted disease risk in Colombia. Population distributions of Colombia's three major ethnic groups - Mestizo, Afro-Colombian, and Indigenous - were compared to disease prevalence and socioeconomic indicators. Indigenous and Mestizo ethnicity show the highest correlations with disease prevalence, whereas the effect of Afro-Colombian ethnicity is substantially lower. Mestizo ethnicity is mostly negatively correlated with six high-impact health conditions and positively correlated with seven of eight common cancers; Indigenous ethnicity shows the opposite effect. Malaria prevalence in particular is strongly correlated with ethnicity. Disease prevalence co-varies across geographic regions, consistent with the regional distribution of ethnic groups. Ethnicity is also correlated with regional variation in human development, partially explaining the observed differences in disease prevalence. Patterns of genetic ancestry and admixture for a cohort of 624 individuals from Medellín were compared to disease risk inferred via polygenic risk scores (PRS). African genetic ancestry is most strongly correlated with predicted disease risk, whereas European and Native American ancestry show weaker effects. African ancestry is mostly positively correlated with disease risk, and European ancestry is mostly negatively correlated. The relationships between ethnicity and disease prevalence do not show an overall correspondence with the relationships between ancestry and disease risk. We discuss possible reasons for the divergent health effects of ethnicity and ancestry as well as the implication of our results for the development of precision medicine in Colombia.

Genomic characterization and computational phenotyping of nitrogen-fixing bacteria isolated from Colombian sugarcane fields.

Previous studies have shown the sugarcane microbiome harbors diverse plant growth promoting microorganisms, including nitrogen-fixing bacteria (diazotrophs), which can serve as biofertilizers. The genomes of 22 diazotrophs from Colombian sugarcane fields were sequenced to investigate potential biofertilizers. A genome-enabled computational phenotyping approach was developed to prioritize sugarcane associated diazotrophs according to their potential as biofertilizers. This method selects isolates that have potential for nitrogen fixation and other plant growth promoting (PGP) phenotypes while showing low risk for virulence and antibiotic resistance. Intact nitrogenase (nif) genes and operons were found in 18 of the isolates. Isolates also encode phosphate solubilization and siderophore production operons, and other PGP genes. The majority of sugarcane isolates showed uniformly low predicted virulence and antibiotic resistance compared to clinical isolates. Six strains with the highest overall genotype scores were experimentally evaluated for nitrogen fixation, phosphate solubilization, and the production of siderophores, gibberellic acid, and indole acetic acid. Results from the biochemical assays were consistent and validated computational phenotype predictions. A genotypic and phenotypic threshold was observed that separated strains by their potential for PGP versus predicted pathogenicity. Our results indicate that computational phenotyping is a promising tool for the assessment of bacteria detected in agricultural ecosystems.

Genetic ancestry and ethnic identity in Ecuador.

We investigated the ancestral origins of four Ecuadorian ethnic groups-Afro-Ecuadorian, Mestizo, Montubio, and the Indigenous Tsáchila-in an effort to gain insight on the relationship between ancestry, culture, and the formation of ethnic identities in Latin America. The observed patterns of genetic ancestry are largely concordant with ethnic identities and historical records of conquest and colonization in Ecuador. Nevertheless, a number of exceptional findings highlight the complex relationship between genetic ancestry and ethnicity in Ecuador. Afro-Ecuadorians show far less African ancestry, and the highest levels of Native American ancestry, seen for any Afro-descendant population in the Americas. Mestizos in Ecuador show high levels of Native American ancestry, with substantially less European ancestry, despite the relatively low Indigenous population in the country. The recently recognized Montubio ethnic group is highly admixed, with substantial contributions from all three continental ancestries. The Tsáchila show two distinct ancestry subgroups, with most individuals showing almost exclusively Native American ancestry and a smaller group showing a Mestizo characteristic pattern. Considered together with historical data and sociological studies, our results indicate the extent to which ancestry and culture interact, often in unexpected ways, to shape ethnic identity in Ecuador.

Absence of mgrB Alleviates Negative Growth Effects of Colistin Resistance in Enterobacter cloacae.

Colistin is an important last-line antibiotic to treat highly resistant Enterobacter infections. Resistance to colistin has emerged among clinical isolates but has been associated with a significant growth defect. Here, we describe a clinical Enterobacter isolate with a deletion of mgrB, a regulator of colistin resistance, leading to high-level resistance in the absence of a growth defect. The identification of a path to resistance unrestrained by growth defects suggests colistin resistance could become more common in Enterobacter.

The Phenotypic Consequences of Genetic Divergence between Admixed Latin American Populations: Antioquia and Chocó, Colombia.

Genome-wide association studies have uncovered thousands of genetic variants that are associated with a wide variety of human traits. Knowledge of how trait-associated variants are distributed within and between populations can provide insight into the genetic basis of group-specific phenotypic differences, particularly for health-related traits. We analyzed the genetic divergence levels for 1) individual trait-associated variants and 2) collections of variants that function together to encode polygenic traits, between two neighboring populations in Colombia that have distinct demographic profiles: Antioquia (Mestizo) and Chocó (Afro-Colombian). Genetic ancestry analysis showed 62% European, 32% Native American, and 6% African ancestry for Antioquia compared with 76% African, 10% European, and 14% Native American ancestry for Chocó, consistent with demography and previous results. Ancestry differences can confound cross-population comparison of polygenic risk scores (PRS); however, we did not find any systematic bias in PRS distributions for the two populations studied here, and population-specific differences in PRS were, for the most part, small and symmetrically distributed around zero. Both genetic differentiation at individual trait-associated single nucleotide polymorphisms and population-specific PRS differences between Antioquia and Chocó largely reflected anthropometric phenotypic differences that can be readily observed between the populations along with reported disease prevalence differences. Cases where population-specific differences in genetic risk did not align with observed trait (disease) prevalence point to the importance of environmental contributions to phenotypic variance, for both infectious and complex, common disease. The results reported here are distributed via a web-based platform for searching trait-associated variants and PRS divergence levels at http://map.chocogen.com (last accessed August 12, 2020).

STing: accurate and ultrafast genomic profiling with exact sequence matches.

Genome-enabled approaches to molecular epidemiology have become essential to public health agencies and the microbial research community. We developed the algorithm STing to provide turn-key solutions for molecular typing and gene detection directly from next generation sequence data of microbial pathogens. Our implementation of STing uses an innovative k-mer search strategy that eliminates the computational overhead associated with the time-consuming steps of quality control, assembly, and alignment, required by more traditional methods. We compared STing to six of the most widely used programs for genome-based molecular typing and demonstrate its ease of use, accuracy, speed and efficiency. STing shows superior accuracy and performance for standard multilocus sequence typing schemes, along with larger genome-scale typing schemes, and it enables rapid automated detection of antimicrobial resistance and virulence factor genes. STing determines the sequence type of traditional 7-gene MLST with 100% accuracy in less than 10 seconds per isolate. We hope that the adoption of STing will help to democratize microbial genomics and thereby maximize its benefit for public health.

Ancestry effects on type 2 diabetes genetic risk inference in Hispanic/Latino populations.

BACKGROUND: Hispanic/Latino (HL) populations bear a disproportionately high burden of type 2 diabetes (T2D). The ability to predict T2D genetic risk using polygenic risk scores (PRS) offers great promise for improved screening and prevention. However, there are a number of complications related to the accurate inference of genetic risk across HL populations with distinct ancestry profiles. We investigated how ancestry affects the inference of T2D genetic risk using PRS in diverse HL populations from Colombia and the United States (US). In Colombia, we compared T2D genetic risk for the Mestizo population of Antioquia to the Afro-Colombian population of Chocó, and in the US, we compared European-American versus Mexican-American populations. METHODS: Whole genome sequences and genotypes from the 1000 Genomes Project and the ChocoGen Research Project were used for genetic ancestry inference and for T2D polygenic risk score (PRS) calculation. Continental ancestry fractions for HL genomes were inferred via comparison with African, European, and Native American reference genomes, and PRS were calculated using T2D risk variants taken from multiple genome-wide association studies (GWAS) conducted on cohorts with diverse ancestries. A correction for ancestry bias in T2D risk inference based on the frequencies of ancestral versus derived alleles was developed and applied to PRS calculations in the HL populations studied here. RESULTS: T2D genetic risk in Colombian and US HL populations is positively correlated with African and Native American ancestry and negatively correlated with European ancestry. The Afro-Colombian population of Chocó has higher predicted T2D risk than Antioquia, and the Mexican-American population has higher predicted risk than the European-American population. The inferred relative risk of T2D is robust to differences in the ancestry of the GWAS cohorts used for variant discovery. For trans-ethnic GWAS, population-specific variants and variants with same direction effects across populations yield consistent results. Nevertheless, the control for bias in T2D risk prediction confirms that explicit consideration of genetic ancestry can yield more reliable cross-population genetic risk inferences. CONCLUSIONS: T2D associations that replicate across populations provide for more reliable risk inference, and modeling population-specific frequencies of ancestral and derived risk alleles can help control for biases in PRS estimation.

Admixture-enabled selection for rapid adaptive evolution in the Americas.

BACKGROUND: Admixture occurs when previously isolated populations come together and exchange genetic material. We hypothesize that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we test this hypothesis through the analysis of whole genome sequences sampled from admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico. RESULTS: Our screen for admixture-enabled selection relies on the identification of loci that contain more or less ancestry from a given source population than would be expected given the genome-wide ancestry frequencies. We employ a combined evidence approach to evaluate levels of ancestry enrichment at single loci across multiple populations and multiple loci that function together to encode polygenic traits. We find cross-population signals of African ancestry enrichment at the major histocompatibility locus on chromosome 6, consistent with admixture-enabled selection for enhanced adaptive immune response. Several of the human leukocyte antigen genes at this locus, such as HLA-A, HLA-DRB51, and HLA-DRB5, show independent evidence of positive selection prior to admixture, based on extended haplotype homozygosity in African populations. A number of traits related to inflammation, blood metabolites, and both the innate and adaptive immune system show evidence of admixture-enabled polygenic selection in Latin American populations. CONCLUSIONS: The results reported here, considered together with the ubiquity of admixture in human evolution, suggest that admixture serves as a fundamental mechanism that drives rapid adaptive evolution in human populations.

Analysis of Vibrio cholerae genomes identifies new type VI secretion system gene clusters.

BACKGROUND: Like many bacteria, Vibrio cholerae deploys a harpoon-like type VI secretion system (T6SS) to compete against other microbes in environmental and host settings. The T6SS punctures adjacent cells and delivers toxic effector proteins that are harmless to bacteria carrying cognate immunity factors. Only four effector/immunity pairs encoded on one large and three auxiliary gene clusters have been characterized from largely clonal, patient-derived strains of V. cholerae. RESULTS: We sequence two dozen V. cholerae strain genomes from diverse sources and develop a novel and adaptable bioinformatics tool based on hidden Markov models. We identify two new T6SS auxiliary gene clusters and describe Aux 5 here. Four Aux 5 loci are present in the host strain, each with an atypical effector/immunity gene organization. Structural prediction of the putative effector indicates it is a lipase, which we name TleV1 (type VI lipase effector Vibrio). Ectopic TleV1 expression induces toxicity in Escherichia coli, which is rescued by co-expression of the TliV1a immunity factor. A clinical V. cholerae reference strain expressing the Aux 5 cluster uses TleV1 to lyse its parental strain upon contact via its T6SS but is unable to kill parental cells expressing the TliV1a immunity factor. CONCLUSION: We develop a novel bioinformatics method and identify new T6SS gene clusters in V. cholerae. We also show the TleV1 toxin is delivered in a T6SS manner by V. cholerae and can lyse other bacterial cells. Our web-based tool can be modified to identify additional novel T6SS genomic loci in diverse bacterial species.

Assortative Mating on Ancestry-Variant Traits in Admixed Latin American Populations.

Assortative mating is a universal feature of human societies, and individuals from ethnically diverse populations are known to mate assortatively based on similarities in genetic ancestry. However, little is currently known regarding the exact phenotypic cues, or their underlying genetic architecture, which inform ancestry-based assortative mating. We developed a novel approach, using genome-wide analysis of ancestry-specific haplotypes, to evaluate ancestry-based assortative mating on traits whose expression varies among the three continental population groups - African, European, and Native American - that admixed to form modern Latin American populations. Application of this method to genome sequences sampled from Colombia, Mexico, Peru, and Puerto Rico revealed widespread ancestry-based assortative mating. We discovered a number of anthropometric traits (body mass, height, and facial development) and neurological attributes (educational attainment and schizophrenia) that serve as phenotypic cues for ancestry-based assortative mating. Major histocompatibility complex (MHC) loci show population-specific patterns of both assortative and disassortative mating in Latin America. Ancestry-based assortative mating in the populations analyzed here appears to be driven primarily by African ancestry. This study serves as an example of how population genomic analyses can yield novel insights into human behavior.

Whole-Genome Sequences of Staphylococcus aureus Isolates from Cystic Fibrosis Lung Infections.

Staphylococcus aureus is an early colonizer in the lungs of individuals with cystic fibrosis (CF), but surprisingly, only a limited number of genomes from CF-associated S. aureus isolates have been sequenced. Here, we present the whole-genome sequences of 65 S. aureus isolates obtained from 50 individuals with CF.

Characterization of a nontypeable Haemophilus influenzae thermonuclease.

Nontypeable Haemophilus influenzae (NTHi) has been shown to form biofilms, comprised of extracellular DNA (eDNA), in the middle ear and bronchus during clinical infections. Studies in our laboratory have shown that NTHi possesses a homolog of Staphylococcus aureus thermonuclease (staphylococcal thermonuclease), NTHi nuclease (NTHi Nuc, HI_1296). This enzyme had similar size, heat stability, and divalent cation requirements to those of the staphylococcal homolog as determined by light scattering and circular dichroism spectroscopy. Small angle X-ray scattering (SAXS) analysis suggested an overall shape and substrate-binding site comparable to those of staphylococcal nuclease. However, NTHi Nuc was approximately 25-fold more active in fluorescence resonance energy transfer (FRET) activity assay than staphylococcal thermonuclease. Homology modeling implicates shorter NTHi Nuc loops near the active site for this enhanced activity.

GlobAl Distribution of GEnetic Traits (GADGET) web server: polygenic trait scores worldwide.

Human populations from around the world show striking phenotypic variation across a wide variety of traits. Genome-wide association studies (GWAS) are used to uncover genetic variants that influence the expression of heritable human traits; accordingly, population-specific distributions of GWAS-implicated variants may shed light on the genetic basis of human phenotypic diversity. With this in mind, we developed the GlobAl Distribution of GEnetic Traits web server (GADGET http://gadget.biosci.gatech.edu). The GADGET web server provides users with a dynamic visual platform for exploring the relationship between worldwide genetic diversity and the genetic architecture underlying numerous human phenotypes. GADGET integrates trait-implicated single nucleotide polymorphisms (SNPs) from GWAS, with population genetic data from the 1000 Genomes Project, to calculate genome-wide polygenic trait scores (PTS) for 818 phenotypes in 2504 individual genomes. Population-specific distributions of PTS are shown for 26 human populations across 5 continental population groups, with traits ordered based on the extent of variation observed among populations. Users of GADGET can also upload custom trait SNP sets to visualize global PTS distributions for their own traits of interest.

Genome Sequences of 15 Klebsiella sp. Isolates from Sugarcane Fields in Colombia's Cauca Valley.

Members of the Klebsiella genus promote plant growth. We report here draft whole-genome sequences for 15 Klebsiella sp. isolates from sugarcane fields in the Cauca Valley of Colombia. The genomes of these isolates were characterized as part of a broader effort to evaluate their utility as endemic plant growth-promoting biofertilizers.

Influence of genetic ancestry and socioeconomic status on type 2 diabetes in the diverse Colombian populations of Chocó and Antioquia.

Differences in genetic ancestry and socioeconomic status (SES) among Latin American populations have been linked to health disparities for a number of complex diseases, such as diabetes. We used a population genomic approach to investigate the role that genetic ancestry and socioeconomic status (SES) play in the epidemiology of type 2 diabetes (T2D) for two Colombian populations: Chocó (Afro-Latino) and Antioquia (Mestizo). Chocó has significantly higher predicted genetic risk for T2D compared to Antioquia, and the elevated predicted risk for T2D in Chocó is correlated with higher African ancestry. Despite its elevated predicted genetic risk, the population of Chocó has a three-times lower observed T2D prevalence than Antioquia, indicating that environmental factors better explain differences in T2D outcomes for Colombia. Chocó has substantially lower SES than Antioquia, suggesting that low SES in Chocó serves as a protective factor against T2D. The combination of lower prevalence of T2D and lower SES in Chocó may seem surprising given the protective nature of elevated SES in many populations in developed countries. However, low SES has also been documented to be a protective factor in rural populations in less developed countries, and this appears to be the case when comparing Chocó to Antioquia.

RampDB: a web application and database for the exploration and prediction of receptor activity modifying protein interactions.

Database URL: http://rampdb.biology.gatech.edu.