Learning virulence-transmission relationships using causal inference

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Hauptverfasser: Surasinghe, Sudam, Ogbunugafor, C. Brandon
Format: Preprint
Veröffentlicht: 2026
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author Surasinghe, Sudam
Ogbunugafor, C. Brandon
author_facet Surasinghe, Sudam
Ogbunugafor, C. Brandon
contents The relationship between traits that influence pathogen virulence and transmission is part of the central canon of the evolution and ecology of infectious disease. However, identifying directional and mechanistic relationships among traits remains a key challenge in various subfields of biology, as models often assume static, fixed links between characteristics. Here, we introduce learning evolutionary trait relationships (LETR), a data-driven framework that applies Granger-causality principles to determine which traits drive others and how these relationships change over time. LETR integrates causal discovery with generative mapping and transfer-operator analysis to link short-term predictability with long-term trait distributions. Using a synthetic myxomatosis virus-host data set, we show that LETR reliably recovers known directional influences, such as virulence driving transmission. Applying the framework to global pandemic (SARS-CoV-2) data, we find that past virulence improves future transmission prediction, while the reverse effect is weak. Invariant-density estimates reveal a long-term trend toward low virulence and transmission, with bimodality in virulence suggesting ecological influences or host heterogeneity. In summary, this study provides a blueprint for learning the relationship between how harmful a pathogen is and how well it spreads, which is highly idiosyncratic and context-dependent. This finding undermines simplistic models and encourages the development of new theory for the constraints underlying pathogen evolution. Further, by uniting causal inference with dynamical modeling, the LETR framework offers a general approach for uncovering mechanistic trait linkages in complex biological systems of various kinds.
format Preprint
id arxiv_https___arxiv_org_abs_2602_05196
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Learning virulence-transmission relationships using causal inference
Surasinghe, Sudam
Ogbunugafor, C. Brandon
Populations and Evolution
Quantitative Methods
The relationship between traits that influence pathogen virulence and transmission is part of the central canon of the evolution and ecology of infectious disease. However, identifying directional and mechanistic relationships among traits remains a key challenge in various subfields of biology, as models often assume static, fixed links between characteristics. Here, we introduce learning evolutionary trait relationships (LETR), a data-driven framework that applies Granger-causality principles to determine which traits drive others and how these relationships change over time. LETR integrates causal discovery with generative mapping and transfer-operator analysis to link short-term predictability with long-term trait distributions. Using a synthetic myxomatosis virus-host data set, we show that LETR reliably recovers known directional influences, such as virulence driving transmission. Applying the framework to global pandemic (SARS-CoV-2) data, we find that past virulence improves future transmission prediction, while the reverse effect is weak. Invariant-density estimates reveal a long-term trend toward low virulence and transmission, with bimodality in virulence suggesting ecological influences or host heterogeneity. In summary, this study provides a blueprint for learning the relationship between how harmful a pathogen is and how well it spreads, which is highly idiosyncratic and context-dependent. This finding undermines simplistic models and encourages the development of new theory for the constraints underlying pathogen evolution. Further, by uniting causal inference with dynamical modeling, the LETR framework offers a general approach for uncovering mechanistic trait linkages in complex biological systems of various kinds.
title Learning virulence-transmission relationships using causal inference
topic Populations and Evolution
Quantitative Methods
url https://arxiv.org/abs/2602.05196