Asset Details
Do you wish to reserve the book?
Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood
Do you wish to request the book?
Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood
2021
Overview
Age-related clonal hematopoiesis (ARCH) is characterized by age-associated accumulation of somatic mutations in hematopoietic stem cells (HSCs) or their pluripotent descendants. HSCs harboring driver mutations will be positively selected and cells carrying these mutations will rise in frequency. While ARCH is a known risk factor for blood malignancies, such as Acute Myeloid Leukemia (AML), why some people who harbor ARCH driver mutations do not progress to AML remains unclear. Here, we model the interaction of positive and negative selection in deeply sequenced blood samples from individuals who subsequently progressed to AML, compared to healthy controls, using deep learning and population genetics. Our modeling allows us to discriminate amongst evolutionary classes with high accuracy and captures signatures of purifying selection in most individuals. Purifying selection, acting on benign or mildly damaging passenger mutations, appears to play a critical role in preventing disease-predisposing clones from rising to dominance and is associated with longer disease-free survival. Through exploring a range of evolutionary models, we show how different classes of selection shape clonal dynamics and health outcomes thus enabling us to better identify individuals at a high risk of malignancy.
Age-related clonal hematopoiesis is associated with risk for diseases like acute myeloid leukemia (AML), yet it is unclear why some individuals do not progress despite having AML driver mutations. Here, the authors use deep learning and population genetics models to investigate how the interplay of positive and negative selection influences AML progression.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Adult
/ Age
/ Aged
/ Aging
/ Arches
/ Blood
/ Clonal Hematopoiesis - genetics
/ Genetics
/ Genetics, Population - methods
/ Genetics, Population - statistics & numerical data
/ Hematopoietic Stem Cells - cytology
/ Hematopoietic Stem Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Leukemia
/ Leukemia, Myeloid - genetics
/ Leukemia, Myeloid - pathology
/ Mutation
/ Outcome Assessment, Health Care - methods
/ Outcome Assessment, Health Care - statistics & numerical data
/ Science
