Elife. 2024 Nov 13;13:RP95170. doi: 10.7554/eLife.95170.

ABSTRACT

Enhancers and promoters are classically considered to be bound by a small set of transcription factors (TFs) in a sequence-specific manner. This assumption has come under increasing skepticism as the datasets of ChIP-seq assays of TFs have expanded. In particular, high-occupancy target (HOT) loci attract hundreds of TFs with often no detectable correlation between ChIP-seq peaks and DNA-binding motif presence. Here, we used a set of 1003 TF ChIP-seq datasets (HepG2, K562, H1) to analyze the patterns of ChIP-seq peak co-occurrence in combination with functional genomics datasets. We identified 43,891 HOT loci forming at the promoter (53%) and enhancer (47%) regions. HOT promoters regulate housekeeping genes, whereas HOT enhancers are involved in tissue-specific process regulation. HOT loci form the foundation of human super-enhancers and evolve under strong negative selection, with some of these loci being located in ultraconserved regions. Sequence-based classification analysis of HOT loci suggested that their formation is driven by the sequence features, and the density of mapped ChIP-seq peaks across TF-bound loci correlates with sequence features and the expression level of flanking genes. Based on the affinities to bind to promoters and enhancers we detected five distinct clusters of TFs that form the core of the HOT loci. We report an abundance of HOT loci in the human genome and a commitment of 51% of all TF ChIP-seq binding events to HOT locus formation thus challenging the classical model of enhancer activity and propose a model of HOT locus formation based on the existence of large transcriptional condensates.

PMID:39535534 | DOI:10.7554/eLife.95170

Elife. 2024 Nov 13;13:RP97279. doi: 10.7554/eLife.97279.

ABSTRACT

Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here, we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis. Splenic injection of Dkk2 knockout (KO) cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases. Transcriptome analysis showed reduction of Paneth cell markers such as lysozymes in KO organoids. Single-cell RNA sequencing analyses of murine metastasized colon cancer cells and patient samples identified the presence of lysozyme positive cells with Paneth cell properties including enhanced glycolysis. Further analyses of transcriptome and chromatin accessibility suggested hepatocyte nuclear factor 4 alpha (HNF4A) as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing analysis revealed that HNF4A binds to the promoter region of Sox9, a well-known transcription factor for Paneth cell differentiation. In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers.

PMID:39535280 | DOI:10.7554/eLife.97279

J Biomol Struct Dyn. 2024 Nov 13:1-15. doi: 10.1080/07391102.2024.2425840. Online ahead of print.

ABSTRACT

Non-small-cell lung cancer (NSCLC) is one of the most deadly tumors characterized by poor survival rates. Advances in therapeutics and precise identification of biomarkers can potentially reduce the mortality rate. Thus, this study aimed to identify a set of common and stable gene biomarkers through integrated bioinformatics approaches that might be effective for NSCLC early diagnosis, prognosis, and therapies. Four gene expression profiles (GSE19804, GSE19188, GSE10072, and GSE32863) downloaded from the Gene Expression Omnibus database to identify common differential expressed genes (DEGs). A total of 213 overlapping DEGs (oDEGs) between NSCLC and healthy samples were identified by using statistical LIMMA method. Then 6 common top-ranked key genes (KGs) (CENPF, CAV1, ASPM, CCNB2, PRC1, and KIAA0101) were selected by using four network-measurer methods in the protein- protein interaction network. The GO functional and KEGG pathway enrichment analysis were performed to reveal some significant functions and pathways associated with NSCLC progression. Transcriptional and post-transcriptional factors of KGs were identified through the regulatory interaction network. The prognostic power and expression level of KGs were validated by using the independent data through the Kaplan-Meier and Box plots, respectively. Finally, 4 KGs-guided repositioning candidate drugs (ZSTK474, GSK2126458, Masitinib, and Trametinib) were proposed. The stability of three top-ranked drug-target interactions (CAV1 vs. ZSTK474, CAV1 vs. GSK2126458, and ASPM vs. Trametinib) were investigated by computing their binding free energies for 140 ns MD-simulation based on MM-PBSA approach. Therefore, the findings of this computational study may be useful for early prognosis, diagnosis and therapies of NSCLC.

PMID:39535278 | DOI:10.1080/07391102.2024.2425840

Nucleic Acids Res. 2024 Nov 13:gkae1013. doi: 10.1093/nar/gkae1013. Online ahead of print.

ABSTRACT

Spermatogonial stem cells (SSCs) play crucial roles in the preservation of male fertility. However, successful ex vivo expansion of authentic human SSCs remains elusive due to the inadequate understanding of SSC homeostasis regulation. Using rhesus monkeys (Macaca mulatta) as a representative model, we characterized SSCs and progenitor subsets through single-cell RNA sequencing using a cell-specific network approach. We also profiled chromatin status and major histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K9me3), and subsequently mapped promoters and active enhancers in TSPAN33+ putative SSCs. Comparing the epigenetic changes between fresh TSPAN33+ cells and cultured TSPAN33+ cells (resembling progenitors), we identified the regulatory elements with higher activity in SSCs, and the potential transcription factors and signaling pathways implicated in SSC regulation. Specifically, TGF-β signaling is activated in monkey putative SSCs. We provided evidence supporting its role in promoting self-renewal of monkey SSCs in culture. Overall, this study outlines the epigenetic landscapes of monkey SSCs and provides clues for optimization of the culture condition for primate SSCs expansion.

PMID:39535033 | DOI:10.1093/nar/gkae1013

PNAS Nexus. 2024 Nov 12;3(11):pgae456. doi: 10.1093/pnasnexus/pgae456. eCollection 2024 Nov.

ABSTRACT

Digital twins offer a new and exciting framework that has recently attracted significant interest in fields such as oncology, immunology, and cardiology. The basic idea of a digital twin is to combine simulation and learning to create a virtual model of a physical object. In this paper, we explore how the concept of digital twins can be generalized into a broader, overarching field. From a theoretical standpoint, this generalization is achieved by recognizing that the duality of a digital twin fundamentally connects complexity science with data science, leading to the emergence of complexity data science as a synthesis of the two. We examine the broader implications of this field, including its historical roots, challenges, and opportunities.

PMID:39534652 | PMC:PMC11555686 | DOI:10.1093/pnasnexus/pgae456

MedComm (2020). 2024 Nov 11;5(11):e792. doi: 10.1002/mco2.792. eCollection 2024 Nov.

ABSTRACT

Identification of therapeutic targets can directly elucidate the mechanism and effect of drug therapy, which is a central step in drug development. The disconnect between protein targets and phenotypes under complex mechanisms hampers comprehensive target understanding. Metabolomics, as a systems biology tool that captures phenotypic changes induced by exogenous compounds, has emerged as a valuable approach for target identification. A comprehensive overview was provided in this review to illustrate the principles and advantages of metabolomics, delving into the application of metabolomics in target identification. This review outlines various metabolomics-based methods, such as dose-response metabolomics, stable isotope-resolved metabolomics, and multiomics, which identify key enzymes and metabolic pathways affected by exogenous substances through dose-dependent metabolite-drug interactions. Emerging techniques, including single-cell metabolomics, artificial intelligence, and mass spectrometry imaging, are also explored for their potential to enhance target discovery. The review emphasizes metabolomics' critical role in advancing our understanding of disease mechanisms and accelerating targeted drug development, while acknowledging current challenges in the field.

PMID:39534557 | PMC:PMC11555024 | DOI:10.1002/mco2.792

IFAC Pap OnLine. 2024;58(15):1-6. doi: 10.1016/j.ifacol.2024.08.495. Epub 2024 Sep 19.

ABSTRACT

This paper addresses the inference challenges associated with a class of hidden Markov models with binary state variables, known as partially observed Boolean dynamical systems (POBDS). POBDS have demonstrated remarkable success in modeling the ON and OFF dynamics of genes, microbes, and bacteria in systems biology, as well as in network security to represent the propagation of attacks among interconnected elements. Despite existing optimal and approximate inference solutions for POBDS, scalability remains a significant issue due to the computational cost associated with likelihood evaluations and the exploration of extensive parameter spaces. To overcome these challenges, this paper proposes a kernel-based particle filtering approach for large-scale inference of POBDS. Our method employs a Gaussian process (GP) to efficiently represent the expensive-to-evaluate likelihood function across the parameter space. The likelihood evaluation is approximated using a particle filtering technique, enabling the GP to account for various sources of uncertainty, including limited likelihood evaluations. Leveraging the GP's predictive behavior, a Bayesian optimization strategy is derived for effectively seeking parameters yielding the highest likelihood, minimizing the overall computational burden while balancing exploration and exploitation. The proposed method's performance is demonstrated using two biological networks: the mammalian cell-cycle network and the T-cell large granular lymphocyte leukemia network.

PMID:39534460 | PMC:PMC11555645 | DOI:10.1016/j.ifacol.2024.08.495

Front Genet. 2024 Oct 29;15:1472638. doi: 10.3389/fgene.2024.1472638. eCollection 2024.

ABSTRACT

INTRODUCTION: The differential ratio of nonsynonymous to synonymous nucleotide substitutions (dN/dS) is a common measure of the rate of structural evolution in proteincoding genes. In addition, we recently suggested that the proportion of transposable elements in gene promoters that host functional genomic sites serves as a marker of the rate of regulatory evolution of genes. Such functional genomic regions may include transcription factor binding sites and modified histone binding loci.

METHODS: Here, we constructed a model of the human interactome based on 600,136 documented molecular interactions and investigated the overall relationship between the number of interactions of each protein and the rate of structural and regulatory evolution of the corresponding genes.

RESULTS: By evaluating a total of 4,505 human genes and 1,936 molecular pathways we found a general correlation between structural and regulatory evolution rate metrics (Spearman 0.08-0.16 and 0.25-0.37 for gene and pathway levels, respectively, p < 0.01). Further exploration revealed in the established human interactome model lack of correlation between the rate of gene regulatory evolution and the number of protein interactions on gene level, and weak negative correlation (∼0.15) on pathway level. We also found a statistically significant negative correlation between the rate of gene structural evolution and the number of protein interactions (Spearman -0.11 and -0.3 for gene and pathway levels, respectively, p < 0.01).

DISCUSSION: Our result suggests stronger structural rather than regulatory conservation of genes whose protein products have multiple interaction partners.

PMID:39534081 | PMC:PMC11554504 | DOI:10.3389/fgene.2024.1472638

Plant Biotechnol J. 2024 Nov 12. doi: 10.1111/pbi.14504. Online ahead of print.

ABSTRACT

Flooding is a widespread natural disaster that causes tremendous yield losses of global food production. Rice is the only cereal capable of growing in aquatic environments. Direct seeding by which seedlings grow underwater is an important cultivation method for reducing rice production cost. Hypoxic germination tolerance and root growth in waterlogged soil are key traits for rice adaptability to flooded environments. Alternative oxidase (AOX) is a non-ATP-producing terminal oxidase in the plant mitochondrial electron transport chain, but its role in hypoxia tolerance had been unclear. We have discovered that AOX1a is necessary and sufficient to promote germination/coleoptile elongation and root development in rice under flooding/hypoxia. Hypoxia enhances endogenous H2O2 accumulation, and H2O2 in turn activates an ensemble of regulatory genes including AOX1a to facilitate the conversion of deleterious reactive oxygen species to H2O2 in rice under hypoxia. We show that AOX1a and H2O2 act interdependently to coordinate three key downstream events, that is, glycolysis/fermentation for minimal ATP production, root aerenchyma development and lateral root emergence under hypoxia. Moreover, we reveal that ectopic AOX1a expression promotes vigorous root and plant growth, and increases grain yield under regular irrigation conditions. Our discoveries provide new insights into a unique sensor-second messenger pair in which AOX1a acts as the sensor perceiving low oxygen tension, while H2O2 accumulation serves as the second messenger triggering downstream root development in rice against hypoxia stress. This work also reveals AOX1a genetic manipulation and H2O2 pretreatment as potential targets for improving flooding tolerance in rice and other crops.

PMID:39533537 | DOI:10.1111/pbi.14504

Stem Cell Res Ther. 2024 Nov 13;15(1):420. doi: 10.1186/s13287-024-04009-3.

ABSTRACT

BACKGROUND: Congenital heart defects can lead to right ventricular (RV) pressure-overload and heart failure. Cell-based therapies, including mesenchymal stromal cells (MSCs) and c-kit positive cells (CPCs) have been studied clinically as options to restore heart function in disease states. Many studies have indicated these cells act through paracrine mechanisms to prevent apoptosis, promote cellular function, and regulate gene/protein expression. We aimed to determine the proteomic response of diseased hearts to cell therapy.

METHODS: We utilized a juvenile rat model of RV pressure overload created by banding the pulmonary artery (PAB). Two weeks post-banding, bone marrow-derived mesenchymal stromal cells (MSCs) and 3 populations of CPCs (nCPCs, cCPCs, ES-CPCs) were delivered to the RV free wall. RV function and cellular retention were measured for four weeks post-injection, at which point hearts were extracted and the RV was excised for liquid chromatography and tandem mass spectrometry. Resulting RV proteomes were compared and analyzed using systems biology and bioinformatics.

RESULTS: Proteomic profiling identified 1156 total proteins from the RV, of which 5.97% were significantly changed after PAB. This disease-altered proteome was responsive to cellular therapy, with 72% of the PAB-altered proteome being fully or partially reversed by MSC therapy. This was followed by nCPCs (54%), ES-CPCs (52%), and cCPCs (39%). Systems biology and bioinformatics analysis showed MSC, nCPC, or ES-CPC cell therapy is associated with a decrease in predicted adverse cardiac effects. We also observed an effect of cell therapy on the non-altered RV proteome, however, this was associated with minor predicted pathological endpoints.

CONCLUSIONS: Our data indicate MSCs, ES-CPCs, and nCPCs significantly reverse the PAB-altered proteome towards a pre-disease state in our animal model. These results indicate cell-based therapies show promise in improving RV function after pressure overload through partial restoration of the disease-altered cardiac proteome.

PMID:39533351 | DOI:10.1186/s13287-024-04009-3

Nature. 2024 Nov 12. doi: 10.1038/s41586-024-08084-7. Online ahead of print.

NO ABSTRACT

PMID:39533066 | DOI:10.1038/s41586-024-08084-7

Sci Rep. 2024 Nov 12;14(1):27681. doi: 10.1038/s41598-024-78965-4.

ABSTRACT

We investigated the long-term effects of prenatal nutrition on pre-slaughter Nelore bulls using integrative transcriptome and metabolome analyses of liver tissue. Three prenatal nutritional treatments were administered to 126 cows: NP (control, mineral supplementation only), PP (protein-energy supplementation in the third trimester), and FP (protein-energy supplementation throughout pregnancy). Liver samples from 22.5 ± 1-month-old bulls underwent RNA-Seq and targeted metabolomics. Weighted correlation network analysis (WGCNA) identified treatment-associated gene and metabolite co-expression modules, further analyzed using MetaboAnalyst 6.0 (metabolite over-representation analysis and transcriptome-metabolome integrative analysis) and Enrichr (gene over-representation analysis). We identified several significant gene and metabolite modules, as well as hub components associated with energy, protein and oxidative metabolism, regulatory mechanisms, epigenetics, and immune function. The NP transcriptome-metabolome analysis identified key pathways (aminoacyl t-RNA biosynthesis, gluconeogenesis, and PPAR signaling) and hub components (glutamic acid, SLC6A14). PP highlighted pathways (arginine and proline metabolism, TGF-beta signaling, glyoxylate and dicarboxylate metabolism) with arginine and ODC1 as hub components. This study highlights the significant impact of prenatal nutrition on the liver tissue of Nelore bulls, shedding light on critical metabolic pathways and hub components related to energy and protein metabolism, as well as immune system and epigenetics.

PMID:39532951 | DOI:10.1038/s41598-024-78965-4

J Ethnopharmacol. 2024 Nov 10:119044. doi: 10.1016/j.jep.2024.119044. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of depression and anxiety is high during pregnancy. Several traditional medicines use the plant Kalanchoe pinnata (Lam.) Pers. (KP) to treat emotional disorders, inflammation, and to prevent preterm delivery, but the effects on the exposed offspring and the mechanism behind these events remain unknown.

AIM OF THE STUDY: In this work, integrated systems toxicology (INSYSTA) was used to investigate traditional toxicological outcomes and behavioral performance in zebrafish larvae after chronic exposure (from 2 to 96 hpf) to K. pinnata leaf extracts (KPL).

MATERIALS AND METHODS: We investigated light/dark preference, thigmotaxis and locomotor activity parameters, followed by gene expression and systems biology approaches to discover the mechanisms behind toxicological endpoint and phenomics.

RESULTS: The embryos exposed to 700 mg/L KPL showed retarded development including hatching delay. Larvae exposed to 500 mg/L KPL resulted in decreased dark avoidance and increased locomotor activity, while 700 mg/L showed opposite effects. The INSYSTA revealed sixteen genes down-regulated after KPL chronic treatment; they are involved in folding, sorting, and degradation of proteins as well as DNA replication and repair mechanisms. This may result in deregulation of the organismal functions, including those of immune and endocrine systems. These physiological changes appear to make embryos more sensitive to infections and disorders that resemble 47 human diseases.

CONCLUSION: These findings suggest that the medicinal use of plant extracts requires strict toxicological, pharmacological, and medical supervision. At the same time, it suggests a polypharmacological pathway for KPL extract that goes beyond preventing premature delivery and controlling anxiety.

PMID:39532221 | DOI:10.1016/j.jep.2024.119044

Cell. 2024 Nov 11:S0092-8674(24)01159-0. doi: 10.1016/j.cell.2024.10.011. Online ahead of print.

ABSTRACT

Quantifying spatiotemporal dynamics during embryogenesis is crucial for understanding congenital diseases. We developed Spateo (https://github.com/aristoteo/spateo-release), a 3D spatiotemporal modeling framework, and applied it to a 3D mouse embryogenesis atlas at E9.5 and E11.5, capturing eight million cells. Spateo enables scalable, partial, non-rigid alignment, multi-slice refinement, and mesh correction to create molecular holograms of whole embryos. It introduces digitization methods to uncover multi-level biology from subcellular to whole organ, identifying expression gradients along orthogonal axes of emergent 3D structures, e.g., secondary organizers such as midbrain-hindbrain boundary (MHB). Spateo further jointly models intercellular and intracellular interaction to dissect signaling landscapes in 3D structures, including the zona limitans intrathalamica (ZLI). Lastly, Spateo introduces "morphometric vector fields" of cell migration and integrates spatial differential geometry to unveil molecular programs underlying asymmetrical murine heart organogenesis and others, bridging macroscopic changes with molecular dynamics. Thus, Spateo enables the study of organ ecology at a molecular level in 3D space over time.

PMID:39532097 | DOI:10.1016/j.cell.2024.10.011

Mol Biol Evol. 2024 Nov 12:msae240. doi: 10.1093/molbev/msae240. Online ahead of print.

ABSTRACT

The Transcriptional Regulatory Network (TRN) in bacteria is thought to rapidly evolve in response to selection pressures, modulating transcription factor (TF) activities and interactions. In order to probe the limits and mechanisms surrounding the short-term adaptability of the TRN, we generated, evolved, and characterized knockout (KO) strains in E. coli for 11 regulators selected based on measured growth impact on glucose minimal media. All but one knockout strain (Δlrp) were able to recover growth and did so requiring few convergent mutations. We found that the TF knockout adaptations could be divided into four categories: 1) Strains (ΔargR, ΔbasR, Δlon, ΔzntR, Δzur) that recovered growth without any regulator-specific adaptations, likely due to minimal activity of the regulator on the growth condition, 2) Strains (ΔcytR, ΔmlrA, ΔybaO) that recovered growth without TF-specific mutations but with differential expression of regulators with overlapping regulons to the KO'ed TF, 3) Strains (Δcrp, Δfur) that recovered growth using convergent mutations within their regulatory networks, including regulated promoters and connected regulators, and 4) Strains (Δlrp) that were unable to fully recover growth, seemingly due to the broad connectivity of the TF within the TRN. Analyzing growth capabilities in evolved and unevolved strains indicated that growth adaptation can restore fitness to diverse substrates often despite a lack of TF-specific mutations. This work reveals the breadth of TRN adaptive mechanisms and suggests these mechanisms can be anticipated based on the network and functional context of the perturbed TFs.

PMID:39531644 | DOI:10.1093/molbev/msae240

Elife. 2024 Nov 12;13:RP96266. doi: 10.7554/eLife.96266.

ABSTRACT

Programmed cell death occurring during plant development (dPCD) is a fundamental process integral for plant growth and reproduction. Here, we investigate the connection between developmentally controlled PCD and fungal accommodation in Arabidopsis thaliana roots, focusing on the root cap-specific transcription factor ANAC033/SOMBRERO (SMB) and the senescence-associated nuclease BFN1. Mutations of both dPCD regulators increase colonization by the beneficial fungus Serendipita indica, primarily in the differentiation zone. smb-3 mutants additionally exhibit hypercolonization around the meristematic zone and a delay of S. indica-induced root-growth promotion. This demonstrates that root cap dPCD and rapid post-mortem clearance of cellular corpses represent a physical defense mechanism restricting microbial invasion of the root. Additionally, reporter lines and transcriptional analysis revealed that BFN1 expression is downregulated during S. indica colonization in mature root epidermal cells, suggesting a transcriptional control mechanism that facilitates the accommodation of beneficial microbes in the roots.

PMID:39531016 | DOI:10.7554/eLife.96266

Microbiol Resour Announc. 2024 Nov 12:e0078924. doi: 10.1128/mra.00789-24. Online ahead of print.

ABSTRACT

During the COVID-19 pandemic, Nepal, like other countries, faced emerging SARS-CoV-2 variants. To evaluate the circulating variants, 278 samples collected between September 2021 and March 2022 were sequenced in the country. From these, 229 high-quality genomes were obtained (82.97% Omicron and 17.03% Delta) highlighting the genomic diversity of SARS-CoV-2 in Nepal.

PMID:39530702 | DOI:10.1128/mra.00789-24

Nucleic Acids Res. 2024 Nov 12:gkae1043. doi: 10.1093/nar/gkae1043. Online ahead of print.

ABSTRACT

The broadly used 10X Genomics technology for single-cell RNA sequencing (scRNA-seq) captures RNA 3' ends. Thus, some reads contain part of the non-templated polyadenosine tails, providing direct evidence for the sites of 3' end cleavage and polyadenylation on the respective RNAs. Taking advantage of this property, we recently developed the SCINPAS workflow to infer polyadenylation sites (PASs) from scRNA-seq data. Here, we used this workflow to construct version 3.0 (v3.0, https://polyasite.unibas.ch/) of the PolyASite Atlas from a big compendium of publicly available human, mouse and worm scRNA-seq datasets obtained from healthy tissues. As the resolution of scRNA-seq was too low for robust detection of cell-level differences in PAS usage, we aggregated samples based on their tissue-of-origin to construct tissue-level catalogs of PASs. These provide qualitatively new information about PAS usage, in comparison to the previous PAS catalogs that were based on bulk 3' end sequencing experiments primarily in cell lines. In the new version, we document stringency levels associated with each PAS so that users can balance sensitivity and specificity in their analysis. We also upgraded the integration with the UCSC Genome Browser and developed track hubs conveniently displaying pooled and tissue-specific expression of PASs.

PMID:39530237 | DOI:10.1093/nar/gkae1043

Open Forum Infect Dis. 2024 Oct 7;11(11):ofae591. doi: 10.1093/ofid/ofae591. eCollection 2024 Nov.

ABSTRACT

BACKGROUND: Households are a major setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but there remains a lack of knowledge regarding the dynamics of viral transmission, particularly in the setting of preexisting SARS-CoV-2 immunity and evolving variants.

METHODS: We conducted a prospective, case-ascertained household transmission study in the greater Boston area in March-July 2022. Anterior nasal swabs, along with clinical and demographic data, were collected for 14 days. Nasal swabs were tested for SARS-CoV-2 by polymerase chain reaction (PCR). Whole genome sequencing was performed on high-titer samples.

RESULTS: We enrolled 33 households in a primary analysis set, with a median participant age of 25 years (range, 2-66 years), 98% of whom had received at least 2 doses of a coronavirus disease 2019 (COVID-19) vaccine. Fifty-eight percent of households had a secondary case during follow-up and the secondary attack rate (SAR) for contacts was 39%. We further examined a strict analysis set of 21 households that had only 1 PCR-positive case at baseline, finding an SAR of 22.5%. Genomic epidemiology further determined that there were multiple sources of infection for household contacts, including the index case and outside introductions. When limiting estimates to only highly probable transmissions given epidemiologic and genomic data, the SAR was 18.4%.

CONCLUSIONS: Household contacts of a person newly diagnosed with COVID-19 are at high risk for SARS-CoV-2 infection in the following 2 weeks. This is, however, not only due to infection from the household index case, but also because the presence of an infected household member implies increased SARS-CoV-2 community transmission.

PMID:39529936 | PMC:PMC11551451 | DOI:10.1093/ofid/ofae591

Front Genet. 2024 Oct 21;15:1466382. doi: 10.3389/fgene.2024.1466382. eCollection 2024.

NO ABSTRACT

PMID:39529846 | PMC:PMC11551999 | DOI:10.3389/fgene.2024.1466382