TY - JOUR
T1 - Inferring the distribution of fitness effects in patient-sampled and experimental virus populations
T2 - two case studies
AU - Morales-Arce, Ana Y.
AU - Johri, Parul
AU - Jensen, Jeffrey D.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to The Genetics Society.
PY - 2022/2
Y1 - 2022/2
N2 - We here propose an analysis pipeline for inferring the distribution of fitness effects (DFE) from either patient-sampled or experimentally-evolved viral populations, that explicitly accounts for non-Wright-Fisher and non-equilibrium population dynamics inherent to pathogens. We examine the performance of this approach via extensive power and performance analyses, and highlight two illustrative applications - one from an experimentally-passaged RNA virus, and the other from a clinically-sampled DNA virus. Finally, we discuss how such DFE inference may shed light on major research questions in virus evolution, ranging from a quantification of the population genetic processes governing genome size, to the role of Hill-Robertson interference in dictating adaptive outcomes, to the potential design of novel therapeutic approaches to eradicate within-patient viral populations via induced mutational meltdown.
AB - We here propose an analysis pipeline for inferring the distribution of fitness effects (DFE) from either patient-sampled or experimentally-evolved viral populations, that explicitly accounts for non-Wright-Fisher and non-equilibrium population dynamics inherent to pathogens. We examine the performance of this approach via extensive power and performance analyses, and highlight two illustrative applications - one from an experimentally-passaged RNA virus, and the other from a clinically-sampled DNA virus. Finally, we discuss how such DFE inference may shed light on major research questions in virus evolution, ranging from a quantification of the population genetic processes governing genome size, to the role of Hill-Robertson interference in dictating adaptive outcomes, to the potential design of novel therapeutic approaches to eradicate within-patient viral populations via induced mutational meltdown.
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U2 - 10.1038/s41437-021-00493-y
DO - 10.1038/s41437-021-00493-y
M3 - Article
C2 - 34987185
AN - SCOPUS:85122282289
SN - 0018-067X
VL - 128
SP - 79
EP - 87
JO - Heredity
JF - Heredity
IS - 2
ER -