Comparing subsampling strategies for efficient pairwise analysis of large pathogen genomic and spatial datasets: An application to Mycobacterium tuberculosis transmission
- 1Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America
- 2College of Public Health, National Taiwan University, Taipei, Taiwan
- 3Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, United States of America
Abstract
Pairwise analysis of genomic and spatial data offers opportunities to identify and estimate the associations between covariates and the transmission of pathogens between individuals. However, such pairwise analyses are computationally intensive, and may not be feasible to conduct given the high dyad count in even moderately sized datasets. Here we compare two approaches to increase the efficiency of pairwise analysis for large datasets. We quantify and compare the performance of divide-and-conquer Bayesian model fitting and pairwise case-control approaches for estimating associations between individual- and pair-level covariates and shared membership in a transmission cluster. We utilize a large dataset (n = 4,154) of spatially-referenced, genomically-sequenced Mycobacterium tuberculosis isolates collected from a single city for this analysis, and conduct simulation studies under three representative tuberculosis genomic clustering settings. Across all simulation studies, the case-control approach produced negligible bias and expected 95% credible interval coverage, and performed comparably to the divide-and-conquer approach, with a somewhat narrower distribution of bias estimates and fewer outliers when effect sizes were large. Thus, we recommend using the case-control approach with five controls per case to downscale datasets for pairwise analysis when analysis of the entire dataset is not possible. This approach mitigates the computational challenges of pairwise Bayesian modeling on datasets that require significant computational resources while maintaining desired inferential properties. Author summary: Pairwise analyses of large datasets to study pathogen transmission are computationally demanding because they typically require simultaneous analysis of each possible pair of individuals in a dataset; as datasets become larger these analyses often are not feasible to conduct even with access to high-performance computing resources. In this work, we compare a case-control approach and divide-and-conquer approaches for more efficient pairwise analysis of large datasets. Using a large dataset of Mycobacterium tuberculosis isolates including genetic and spatial data, we investigate the performance of each method for estimating the associations between host covariates and genetic clustering of isolates. We find that the case-control approach is generally preferred over methods which first divide the data into subsets and then combine results. While additional extensions of these analyses are needed to test the generality of these findings to other data settings, this work provides a practical way forward for the pairwise analysis of large datasets to study pathogen transmission.
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BibTeX
@article{lan2026comparing,
title = {{Comparing subsampling strategies for efficient pairwise analysis of large pathogen genomic and spatial datasets: An application to Mycobacterium tuberculosis transmission}},
author = {Yu Lan and Chieh-Yin Wu and Hsien-Ho Lin and Ted Cohen and Joshua L. Warren},
journal = {PLOS Computational Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pcbi.1014353},
url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014353},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparing subsampling strategies for efficient pairwise analysis of large pathogen genomic and spatial datasets: An application to Mycobacterium tuberculosis transmission
AU - Yu Lan
AU - Chieh-Yin Wu
AU - Hsien-Ho Lin
AU - Ted Cohen
AU - Joshua L. Warren
PY - 2026
DA - 2026/09/23
JO - PLOS Computational Biology
DO - 10.1371/journal.pcbi.1014353
UR - https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014353
AB - Pairwise analysis of genomic and spatial data offers opportunities to identify and estimate the associations between covariates and the transmission of pathogens between individuals. However, such pairwise analyses are computationally intensive, and may not be feasible to conduct given the high dyad count in even moderately sized datasets. Here we compare two approaches to increase the efficiency of pairwise analysis for large datasets. We quantify and compare the performance of divide-and-conquer Bayesian model fitting and pairwise case-control approaches for estimating associations between individual- and pair-level covariates and shared membership in a transmission cluster. We utilize a large dataset (n = 4,154) of spatially-referenced, genomically-sequenced Mycobacterium tuberculosis isolates collected from a single city for this analysis, and conduct simulation studies under three representative tuberculosis genomic clustering settings. Across all simulation studies, the case-control approach produced negligible bias and expected 95% credible interval coverage, and performed comparably to the divide-and-conquer approach, with a somewhat narrower distribution of bias estimates and fewer outliers when effect sizes were large. Thus, we recommend using the case-control approach with five controls per case to downscale datasets for pairwise analysis when analysis of the entire dataset is not possible. This approach mitigates the computational challenges of pairwise Bayesian modeling on datasets that require significant computational resources while maintaining desired inferential properties. Author summary: Pairwise analyses of large datasets to study pathogen transmission are computationally demanding because they typically require simultaneous analysis of each possible pair of individuals in a dataset; as datasets become larger these analyses often are not feasible to conduct even with access to high-performance computing resources. In this work, we compare a case-control approach and divide-and-conquer approaches for more efficient pairwise analysis of large datasets. Using a large dataset of Mycobacterium tuberculosis isolates including genetic and spatial data, we investigate the performance of each method for estimating the associations between host covariates and genetic clustering of isolates. We find that the case-control approach is generally preferred over methods which first divide the data into subsets and then combine results. While additional extensions of these analyses are needed to test the generality of these findings to other data settings, this work provides a practical way forward for the pairwise analysis of large datasets to study pathogen transmission.
SN - 1553-7358
ER -