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Informativeness of genetic markers for pairwise relationship and relatedness inference.

Measuring the information content of markers in relationship/relatedness inferences is important in selecting highly informative markers to attain a given statistical power with the minimal genotyping effort. Using information-theoretic principles, I introduce the informativeness for relationship (I(R)) and the informativeness for relatedness (I(r)) to measure the amount of information provided by markers in inferring pairwise relationships (R) and relatedness (r), respectively. I also propose a fast and accurate algorithm to calculate the power (PW(R)) of a set of markers in differentiating two candidate relationships, and the reciprocal of the mean squared deviations of relatedness estimates (RMSD) to measure the amount of information of markers actually used by an estimator in estimating relatedness. All of the four measurements (I(R), I(r), PW(R), RMSD) apply to dominant and codominant markers, haploid and diploid individuals, and take into account of mutations and typing errors in data. The statistical properties of the four measurements and their relationships are investigated analytically and are examined by applying these methods to simulated and empirical data.

Algorithms↗

Few V gene segments dominate the T cell receptor beta-chain repertoire of the human thymus.

We undertook a large sample census of the TCR-beta repertoire from a single human thymus (300 clones from an unamplified cDNA library), to establish the statistics of the rearranged V, D, J, and C gene segments. The assortments of all germ-line segments are subject to significant biases and thus critically reduce the effective germ-line contribution to beta-chain diversity. Thirty-two V genes characterize the whole sample, but surprisingly as few as seven genes from different families encompass half of the beta-chain repertoire. Furthermore, a Spearman rank order correlation test of the thymic V beta frequencies with those inferred in other studies using RNase protection assays shows a statistically significant similarity. Thus, in the establishment of thymic V beta frequencies in man, rearrangement preferences intrinsic to the progenitors of TCR-beta expressing cells override HLA- and Ag-dependent biasing factors. By implication, a large enough pool of direct progenitor cells (maybe as high as thousands) must exist to secure V beta frequencies against large random fluctuations. Uncorrelated with the V gene bias, the representation of D beta and J beta segments is also far from even. Notably, D beta 1 and J beta 2.1 and 1.2 predominate. Using the above mentioned rank order statistic, we also find that unlike V genes, the bias in the J segment usage carries over into the frequencies of peripheral T lymphocyte populations.

Alternative Splicing↗

Noninvasive blood pressure performance: a reproducible method for quantifying motion artifact tolerance in oscillometry.

Motion artifact tends to degrade oscillometric noninvasive blood pressure measurement (NIBP) accuracy and other aspects of performance (measurement time, patient comfort, false-positive readings). Medical personnel generally have not fully appreciated the extent of these degradations, in part because NIBP provides no waveform display to allow visualization of artifact disruption (unlike the electrocardiography (ECG) and pulse oximetry (SpO2) patient channels). More importantly, the magnitude and frequency of NIBP errors has also gone unappreciated because the auditory noise produced by transport vibration prevents accurate quantification of NIBP accuracy by the traditional auscultatory method. To overcome these problems, a commercially available NIBP simulator was modified to permit the superimposition of repeatable motion artifact waveforms from a function generator onto known patient blood pressure profiles available in the NIBP simulator. The superimposed artifact waveforms had been collected under transport conditions. This methodology enabled comparisons between artifact-free NIBP readings, on the one hand, and artifact-contaminated readings on the other. Monitors under test were subjected to multiple combinations of patient and artifact profiles. Measurement errors were expressed as a percent deviation of the artifact-contaminated readings from the expected (artifact-free) readings. Statistical analyses of the data compared the performance of the different monitor types with nonparametric tests of inference (Kruskal-Wallis H test, Mann-Whitney U test, and chi-squared test). These analyses demonstrated statistically significant differences in performance including accuracy, yield (incidence of values within various error categories), retries, measurement time, and false-positive readings under artifact-only conditions. The method further demonstrated that the monitor using ECG synchronization to filter motion artifact achieved statistically and clinically significant improvements in accuracy without compromising clinical expectations for measurement time. This approach provided a reproducible and quantifiable method by which to assess and differentiate the artifact tolerance of different NIBP technologies.

Artifacts↗

[Methodological issues unsaid in medical research].

Methodology consitutes the study of methods considered as << manners of leading its thought, of establishing or of showing truths according to certain principles and with a certain order >>. We will see that medical << truths >>, knowledge, could be of an extremely different nature: factual knowledge is a simple observation, often with operational vocation\; theoretical knowledge belongs to a coherent whole, it fascines and facilitates our representations of pathologies\; the causal knowledge is often the subject of extreme interrogations in medical practice\; it is of primarily metaphysical nature. These distinctions are not without consequence in methodological terms. Theories are useful because they facilitate the choice of the assumptions to be tested, the variables to be measured and the interpretation of the results of experiments. The risk however exists to be unable to think apart from their framework, and thus to neglect any source of knowledge which they could not integrate. The cause is inaccessible to science\; it will be necessary, in practice, to be limited to the search for variables of upstream on which action of prevention or cure could be undertaken. To establish, to show this medical knowledge, it is necessary to resort to the scientific method by formulating refutable assumptions by reproducible experiments, and that this process involves a belief in the found results. It appears thus that for the same experimental plan, the level of belief and thus the level of proof of the results is a function of the type of measurement carried out (commonplace measurement or of high technicality), of the medical discipline and the media character or not of studied pathology, even of stakes of being able. The medical reproducibility of experiments is problematic since results of these experiments are in general random. This results from the considerable number of variables entering in the determination of human pathologies, and that the majority of these variables are either unknown, or impossible to control. Randomisation makes it possible to give a probabilistic character to this risk: it is then possible to resort to mathematics to carry out statistical tests, to calculate confidence intervals and to profit from a possibility of making inferences with a known margin of error. In the absence of randomisation, it is possible to resort to models\; they imply however the knowledge of statistical methods, reserve, experience and a great intellectual honesty during the interpretation of the results, finally a replication of the experiments is here, more than elsewhere, essential.

Biomedical Research↗

Genotype relative-risks and association tests for nuclear families with missing parental data.

The development of a new method for testing the association of genetic markers with disease is presented. This approach is applicable when sampling nuclear families with one or more affected siblings and when neither, one, or both parents are missing marker genotype data. All siblings, affected and not affected, are used to probabilistically infer the missing parental marker data. A likelihood ratio statistic, which treats marker allele frequencies as nuisance parameters, is presented to test whether all marker relative risks are equal to one (i.e., no marker association). This approach offers a solution to test for marker associations when parents are difficult to obtain.

Algorithms↗

GABAergic neurons in the barrel cortex of the mouse: an analysis using neuronal archetypes.

We describe the morphological types of glutamic acid decarboxylase (GAD) immunoreactive cells in the barrel cortex of the mouse. A method is introduced and applied, which combines qualitative and quantitative criteria to classify these cells through the use of multivariate statistics. With the aid of an interactive computer microscope, 2010 GAD-positive neurons were harvested. Each cell was assigned to one of a set of qualitatively defined classes (archetypes) and further characterized by various morphometric parameters. Through the statistical analysis, new sets of hierarchically ordered archetypes were inferred; these served to classify cells which, due to lack of morphological detail, were unclassifiable using qualitative criteria only. We here report on the characteristics of eight archetypes of GAD-positive neurons, distinguished by means of their size, shape, and orientation and the distribution of their cell bodies over the cortical layers. Some archetypes were observed mostly in the upper layers of the cortex (group I triangular and group I horizontal fusiform cells), others mostly in the lower layers (group II triangular and group II horizontal fusiform cells). Bulb and vertical fusiform, as well as vertical star and horizontal star cells, were present throughout the entire cortical thickness. The star cells formed the two most frequent archetypes. This classification constitutes a baseline which we currently use to elucidate whether differences exist in the birthdates among the GABAergic archetypes within each layer of the mouse barrel cortex.

Animals↗

Branch length heterogeneity leads to nonindependent branch length estimates and can decrease the efficiency of methods of phylogenetic inference.

Branch length estimates play a central role in maximum-likelihood (ML) and minimum-evolution (ME) methods of phylogenetic inference. For various reasons, branch length estimates are not statistically independent under ML or ME. We studied the response of correlations among branch length estimates to the degree of among-branch length heterogeneity (BLH) in the model (true) tree. The frequency and magnitude of (especially negative) correlations among branch length estimates were both shown to increase as BLH increases under simulation and analytically. For ML, we used the correct model (Jukes-Cantor). For ME, we employed ordinary least-squares (OLS) branch lengths estimated under both simple p-distances and Jukes-Cantor distances, analyzed with and without an among-site rate heterogeneity parameter. The efficiency of ME and ML was also shown to decrease in response to increased BLH. We note that the shape of the true tree will in part determine BLH and represents a critical factor in the probability of recovering the correct topology. An important finding suggests that researchers cannot expect that different branches that were in fact the same length will have the same probability of being accurately reconstructed when BLH exists in the overall tree. We conclude that methods designed to minimize the interdependencies of branch length estimates (BLEs) may (1) reduce both the variance and the covariance associated with the estimates and (2) increase the efficiency of model-based optimality criteria. We speculate on possible ways to reduce the nonindependence of BLEs under OLS and ML.

Evolution, Molecular↗

A computationally simple bivariate survival estimator for efficacy and safety.

Both treatment efficacy and safety are typically the primary endpoints in Phase II, and even in some Phase III, clinical trials. Efficacy is frequently measured by time to response, death, or some other milestone event and thus is a continuous, possibly censored, outcome. Safety, however, is frequently measured on a discrete scale; in Eastern Cooperative Oncology Group clinical trial E2290, it was measured as the number of weekly rounds of chemotherapy that were tolerable to colorectal cancer patients. For the joint analysis of efficacy and safety, we propose a non-parametric, computationally simple estimator for the bivariate survival function when one time-to-event is continuous, one is discrete, and both are subject to right-censoring. The bivariate censoring times may depend on each other, but they are assumed to be independent of both event times. We derive a closed-form covariance estimator for the survivor function which allows for inference to be based on any of several possible statistics of interest. In addition, we derive its covariance with respect to calendar time of analysis, allowing for its use in sequential studies.

Antineoplastic Agents↗

Lineage-specific transmission and spatial clustering of Mycobacterium tuberculosis in Kaohsiung, Taiwan, in 2019-23: a population-based genomic study.

BACKGROUND: The epidemiology of tuberculosis in Taiwan has been influenced by the introduction of multiple Mycobacterium tuberculosis lineages and by the ageing of the population. We conducted a population-based study to investigate M tuberculosis transmission in Kaohsiung, a city in southern Taiwan. METHODS: In this study, we performed whole-genome sequencing (WGS) of M tuberculosis isolates from all culture-positive cases of tuberculosis notified in Kaohsiung between Jan 1, 2019 and Dec 31, 2023. We obtained routine epidemiological data for each case collected through the national tuberculosis control programme. We characterised the lineage composition of the isolate collection and evaluated genomic clustering of isolates, defined as a difference of 12 or fewer single-nucleotide polymorphisms. Univariable and multivariable logistic regression analyses were performed to estimate the odds of a case belonging to a genomic cluster based on host factors (age, sex, sputum smear status, and residential region) and pathogen factors (drug resistance status and strain lineage). Spatial aggregation of large genomic clusters (including greater than or equal to ten isolates) was assessed using a non-parametric statistical clustering method. We used a Bayesian transmission tree inference method to explore the patterns of age-dependent transmission. FINDINGS: During the study period, 5667 tuberculosis cases were notified in Kaohsiung, 4916 (86&#xb7;7%) of which were culture-positive. Of these 4916 cases, whole-genome sequencing was successfully performed for 4168 (84&#xb7;8%) isolates. 1219 (29&#xb7;2%) of 4168 individuals were female and 2947 (70&#xb7;7%) were male; the median age was 69&#xb7;7 years (IQR 57&#xb7;4-80&#xb7;7). The dominant lineages were lineage 1 (1749 [42&#xb7;0%] of 4168 isolates), lineage 2 (1510 [36&#xb7;2%]), and lineage 4 (905 [21&#xb7;7%]). 1069 (25&#xb7;6%) of 4168 were genomically linked and formed 287 clusters. Lineage 2 isolates had higher odds (aOR 2&#xb7;15 [95% CI 1&#xb7;80-2&#xb7;52]) than lineage 1 isolates of genomic clustering across all regions, whereas lineage 4 isolates had a significantly higher risk (2&#xb7;75 [1&#xb7;16-6&#xb7;89]) of genomic clustering than lineage 1 only in the rural northeast region, inhabited primarily by indigenous populations. Spatial clustering analysis corroborated these lineage-region interactions. Although younger adults (<35 years) had the highest individual-level odds (5&#xb7;64 [4&#xb7;16-7&#xb7;68]) of clustering in the logistic regression analysis compared with those aged 80 years or older, the transmission inference indicated that individuals aged 55-74 years were responsible for a greater proportion of inferred transmission events, contributing 50&#xb7;8% of all transmission events. INTERPRETATION: This sequencing study revealed that older adults (aged &#x2265;65 years) might have played a substantial and under-recognised role in the transmission of tuberculosis in Taiwan. The lineage-specific clustering and spatial patterns suggested that both pathogen characteristics and host demographics shaped tuberculosis transmission dynamics. These findings support the use of integrated genomic surveillance to guide precision tuberculosis control and motivate further research on age-specific transmission pathways and targeted interventions to advance tuberculosis elimination efforts. FUNDING: Taiwan National Health Research Institutes and Taiwan National Science and Technology Council.

Mycobacterium tuberculosis↗

Evaluating the effects of drugs on behavior and quality of life: an alternative strategy for clinical trials.

Conventional clinical trials involve tests of hypotheses with statistics computed from values of dependent variables alone. An alternative is to test hypotheses with statistics computed from benefit/harm scores that measure longitudinal associations between dose and values of the dependent variables. The proposed standardized measure of benefit/harm quantifies the strength of evidence that a patient did either better or worse while on treatment. A benefit/harm score, particularly when obtained from a randomized, N-of-1 trial, indicates a beneficial or harmful treatment effect for the individual. Benefit/harm scores from samples of patients are evaluated with standard statistical tests, with or without group comparisons, to make inferences about populations. The proposed alternative strategy can yield within-patient indicators of treatment effect that are more reliable, valid, comprehensive, and detailed. This, in turn, could help make many population-based clinical trials more informative, cost-effective, and clinically useful for participants.

Administration, Oral↗

Reconstruction of in vivo time-evolving neuroendocrine dose-response properties unveils admixed deterministic and stochastic elements.

Homeostasis in the intact organism is achieved implicitly by repeated incremental feedback (inhibitory) and feedforward (stimulatory) adjustments enforced via intermittent signal exchange. In separated systems, neurohormone signals act deterministically on target cells via quantifiable effector-response functions. On the other hand, in vivo interglandular signaling dynamics have not been estimable to date. Indeed, experimentally isolating components of an interactive network definitionally disrupts time-sensitive linkages. We implement and validate analytical reconstruction of endogenous effector-response properties via a composite model comprising (i) a deterministic basic feedback and feedforward ensemble structure; (ii) judicious statistical allowance for possible stochastic variability in individual biologically interpretable dose-response properties; and (iii) the sole data requirement of serially observed concentrations of a paired signal (input) and response (output). Application of this analytical strategy to a prototypical neuroendocrine axis in the conscious uninjected horse, sheep, and human (i) illustrates probabilistic estimation of endogenous effector dose-response properties; and (ii) unmasks statistically vivid (2- to 5-fold) random fluctuations in inferred target-gland responsivity within any given pulse train. In conclusion, balanced mathematical formalism allows one to (i) reconstruct deterministic properties of interglandular signaling in the intact mammal and (ii) quantify apparent signal-response variability over short time scales in vivo. The present proof-of-principle experiments introduce a previously undescribed means to estimate time-evolving signal-response relationships without isotope infusion or pathway disruption.

Animals↗

The measurement of biological age.

One of the objectives of gerontological research is to achieve, reproducibly and at will, a verifiable discrepancy between the chronological and biological age of organisms. To accomplish this, the experimenter must be in a position to measure biological age independently. In theory, this can be done in the three ways: by actuarial analysis of large populations, assessment of overall morbidity, or observation of chronic degenerative changes that can be actually measured or graded according to a scale. Of these three approaches, only the last appears to be promising in experimental research. However, not all progressive degenerative changes represent practically useful parameters of biological age. Criteria for their evaluation are presented, and their theoretical prerequisites as well as concrete applications discussed. In a more general way, one has to be aware that biological age is a statistical entity. It cannot be directly observed but only inferred from quantifiable epiphenomena, and is, as such, not measurable like temperature or weight.

Aged↗

DNA sequence variation and the recombinational landscape in Drosophila pseudoobscura: a study of the second chromosome.

The relationship between rates of recombination and DNA sequence polymorphism was analyzed for the second chromosome of Drosophila pseudoobscura. We constructed integrated genetic and physical maps of this chromosome using molecular markers at 10 loci spanning most of its physical length. The total length of the map was 128.2 cM, almost twice that of the homologous chromosome arm (3R) in D. melanogaster. There appears to be very little centromeric suppression of recombination, and rates of recombination are quite uniform across most of the chromosome. Levels of sequence variation (theta(W), based on the number of segregating sites) at seven loci (tropomyosin 1, Rhodopsin 3, Rhodopsin 1, bicoid, Xanthine dehydrogenase, Myosin light chain 1, and ribosomal protein 49) varied from 0.0036 to 0.0167. Generally consistent with earlier studies, the average estimate of theta(W) at total sites is 1.5-fold higher than that in D. melanogaster, while average theta(W) at silent sites is almost 3-fold higher. These estimates of variation were analyzed in the context of a background selection model under the same parameters of mutation rate and selection as have been proposed for D. melanogaster. It is likely that a significant fraction of the higher level of sequence variation in D. pseudoobscura can be explained by differences in regional rates of recombination rather than a larger species-level effective population size. However, the distribution of variation among synonymous, nonsynonymous, and noncoding sites appears to be quite different between the species, making direct comparisons of neutral variation, and hence inferences about effective population size, difficult. Tajima's D statistics for 6 out of the 7 loci surveyed are negative, suggesting that D. pseudoobscura may have experienced a rapid population expansion in the recent past or, alternatively, that slightly deleterious mutations constitute an important component of standing variation in this species.

Animals↗

DNA polymorphism in a worldwide sample of human X chromosomes.

DNA sequence data from humans can provide insight into the history of modern humans and the genetic variability in human populations. We report here a study of human DNA sequence variation at an X-linked noncoding region of 10,346 bp. The sample consists of 62 X chromosomes from Africa, Europe, and Asia. Forty-four polymorphic sites were found among the 62 sequences, resulting in 23 different haplotypes. Statistical analyses of the data led to the following inferences. (1) There is strong evidence of human population expansion in the relatively recent past, and this population expansion has had a significant effect on the pattern of polymorphism at this locus. (2) Non-African populations were unlikely to have been derived from a very small number of African lineages. (3) There was considerable geographic subdivision in the ancient human population, which could be an important reason why many studies failed to detect population expansion. (4) The long-term effective population size of humans is between 12,000 and 15,000. And (5) a non-African specific variant was found at a frequency of 35% in non-Africans, an estimate supported by the genotyping of additional 80 non-African and 106 African X chromosomes. This variant could have arisen in Eurasia more than 140,000 years ago, predating the emergence of modern humans. Moreover, this haplotype and all other haplotypes coalesced to the most recent common ancestor of the sample, which was estimated to be older than 490,000 years. Therefore, this region may have a long history in Eurasia.

Chromosomes, Human, X↗

Design of clinical radiologic research.

The components of clinical research design--the research question, the review of prior research, the study design, the study subjects, the study measurements, the statistical analysis, and the critical analysis--have been discussed. These components relate to the overall philosophy of the research process in the following manner. The driving force behind research is the desire to understand a universal truth (Fig. 6). The research question is formed to reflect the truth sought. Next defined is the specific target population and the phenomena of interest with regard to the sought-after truth. The study is then designed with a study plan detailing timing and location and an intended sample population chosen to reflect the target population. The phenomena of interest are translated into measurable intended variables. Care is needed to identify the systematic error that can be introduced at this stage; outside opinion can be invaluable. The actual study results from the implementation of the study design. The actual subjects may differ from the intended sample population due to a low recruitment rate or a large dropout rate. The actual measurements may differ from the intended variables due to unsuspected confounding variables or random errors. Statistical analysis is performed on the study findings to infer truth within the study. This truth may be affected by random and systematic errors in implementing the study. Truth in the study is then inferred to reflect truth in the universe. Systematic and random errors in study design may affect the validity of that deduction, but that deduction is the only way we have of understanding universal truth.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiology↗

Projecting chronic disease prevalence.

Health and long-term care planning for an aging population is an important and necessary function for both the public and private sector. Unfortunately, efforts at planning have often been limited by difficulties in making estimates and forecasts of chronic disease prevalence in the population. These difficulties are a direct result of the natural history of chronic diseases that normally have long presymptomatic stages. Because of this characteristic, predictions of the magnitude of chronic disease prevalence in the United States often fail to reflect an important dimension of the health state of the population: that there is a sizeable proportion of chronic disease prevalence and risk existing in the population in a preclinical phase. The authors present a strategy for obtaining more complete estimates of chronic disease prevalence. This approach entails the creation of an illness--death model representing the natural history of individual chronic diseases and the application of the model to infer morbidity incidence and prevalence patterns from national mortality statistics. They illustrate the approach with an example of lung cancer and discuss the applications of the outputs of the modeling strategy for health care resource planning.

Actuarial Analysis↗

Development and validation of a CGH microarray for clinical cytogenetic diagnosis.

PURPOSE: We developed a microarray for clinical diagnosis of chromosomal disorders using large insert genomic DNA clones as targets for comparative genomic hybridization (CGH). METHODS: The array contains 362 FISH-verified clones that span genomic regions implicated in over 40 known human genomic disorders and representative subtelomeric clones for each of the 41 clinically relevant human chromosome telomeres. Three or four clones from almost all deletion or duplication genomic regions and three or more clones for each subtelomeric region were included. We tested chromosome microarray analysis (CMA) in a masked fashion by examining genomic DNA from 25 patients who were previously ascertained in a genetic clinic and studied by conventional cytogenetics. A novel software package implemented in the R statistical programming language was developed for normalization, visualization, and inference. RESULTS: The CMA results were entirely consistent with previous cytogenetic and FISH findings. For clone by clone analysis, the sensitivity was estimated to be 96.7% and the specificity was 99.1%. Major advantages of this selected human genome array include the following: interrogation of clinically relevant genomic regions, the ability to test for a wide range of duplication and deletion syndromes in a single analysis, the ability to detect duplications that would likely be undetected by metaphase FISH, and ease of confirmation of suspected genomic changes by conventional FISH testing currently available in the cytogenetics laboratory. CONCLUSION: The array is an attractive alternative to telomere FISH and locus-specific FISH, but it does not include uniform coverage across the arms of each chromosome and is not intended to substitute for a standard karyotype. Limitations of CMA include the inability to detect both balanced chromosome changes and low levels of mosaicism.

Chromosome Aberrations↗

Mapping Sub-National Respiratory Virus Circulation in Cambodia Using Metatranscriptomic Sequencing: A Multi-Center Hospital-Based Surveillance Study.

BACKGROUND: Genomic surveillance can guide early detection of and response to emerging epidemics. Metatranscriptomic sequencing was used to investigate sub-national respiratory virus circulation in Cambodia from 2020 to 2023. METHODS: Nasopharyngeal swabs were collected from individuals aged 2&#x2009;months to 65&#x2009;years with influenza-like illness in four Cambodian hospitals. Metatranscriptomic data were generated by short-read RNA sequencing. Bernoulli space-time scan statistics were used to identify temporal virus clusters. Bayesian inference of phylogenetic trees was used to compute divergence times for temporally clustered, highly represented viruses (influenza A/H3N2 and B, Betacoronavirus 1, respiratory syncytial virus [RSV] A and B), and publicly available global influenza virus genomes. RESULTS: Of 1093 individuals, 499 (45.7%) had detectable respiratory viruses belonging to 68 distinct species. Moderate (N&#x2009;>&#x2009;20) discrete time-clusters were noted of RSV-A (37 cases), Betacoronavirus 1 (21 cases), RSV-B (22 cases), and A/H3N2 (30 cases). The posterior median of time to most recent common ancestor ranged from 0.71&#x2009;years (95% HPD 0.38-1.10) for Betacoronavirus 1 and 1.31&#x2009;years (95% HPD 0.60-3.20) for A/H3N2, to 2.75&#x2009;years (1.82-4.26) for RSV-A and 4.79&#x2009;years (2.39-7.74) for RSV-B. A/H3N2 and influenza B virus genomes mapped to clades 3C.2a1b.2a.2a and Victoria 1A.3a.2, respectively, and inter-mixed with concurrent global strains. CONCLUSIONS: Multiple respiratory viruses circulated at a sub-national level in Cambodia from 2020 to 2023 despite pandemic disruptions. Influenza virus population diversity decreased during the height of lockdown but recovered in mid-2022. Re-emerging influenza strains were distinct from historically circulating strains and clustered with contemporaneous global variants, suggesting multiple external introductions.

Humans↗