Taralynn Mack
A5018911614- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Hemoglobinopathies and Related Disorders
- Chronic Myeloid Leukemia Treatments
- Genomics and Rare Diseases
- Immune cells in cancer
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- Genetics, Bioinformatics, and Biomedical Research
- Plant Disease Resistance and Genetics
- Chromosomal and Genetic Variations
- Evolution and Genetic Dynamics
- Chronic Kidney Disease and Diabetes
- Lymphoma Diagnosis and Treatment
- Renal Diseases and Glomerulopathies
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Parvovirus B19 Infection Studies
- Multiple Myeloma Research and Treatments
- Genetic Associations and Epidemiology
- Obesity, Physical Activity, Diet
- Obesity and Health Practices
Vanderbilt University
2021-2025
Vanderbilt University Medical Center
2022-2024
VA Tennessee Valley Healthcare System
2023
Nashville VA Medical Center
2023
Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued inflammatory gene modifier scan for CHIP-associated CVD among 424,651 UK Biobank participants. CHIP was identified using whole exome sequencing data blood DNA and modeled both as a composite common drivers (DNMT3A, TET2, ASXL1, JAK2) separately. developed predicted expression scores 26 inflammasome-related genes assessed...
Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon in which hematopoietic stem cells acquire mutations select set genes commonly mutated myeloid neoplasia then expand clonally. Current sequencing assays to detect CHIP are not optimized for the detection these variants and can be cost-prohibitive when applied large cohorts or serial sequencing. In this study, an affordable (approximately US $8 per sample), accurate, scalable assay introduced validated....
Abstract Mosaic chromosomal alterations of the autosomes (aut-mCAs) are large structural somatic mutations which cause clonal hematopoiesis and increase cancer risk. Here, we detected aut-mCAs in 1,011,269 participants across four biobanks. Through integrative analysis minimum critical region inherited genetic variation, found that proto-oncogenes exclusively drive gains, tumor suppressors losses, copy-neutral events can be driven by either. We identified three novel risk loci CHI3L2, HLA...
Abstract Clonal hematopoiesis (CH) can be caused by either single gene mutations (eg point in JAK2 causing CHIP) or mosaic chromosomal alterations (e.g., loss of heterozygosity at chromosome 9p). CH is associated with a significantly increased risk hematologic malignancies. However, the absolute rate transformation on an annualized basis low. Improved prognostication urgently needed for routine clinical practice. We hypothesized that co-occurrence CHIP and mCAs same locus transforming...
Abstract Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain better understanding mCA rates genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals the National Heart, Lung, and Blood Institute Trans-Omics Precision Medicine program. We observed higher sensitivity with data, compared array-based uncovering mCAs at low mutant cell fractions found that European ancestry have...
Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is a common form age-related somatic mosaicism that associated with significant morbidity and mortality. CHIP mutations can be identified in peripheral blood samples sequenced using approaches cover the whole genome, exome or targeted genetic regions; however, differentiating true from sequencing artifacts germline variants considerable bioinformatic challenge. We present stepwise method combines filtering based on metrics,...
Abstract Purpose: Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk malignancy, including hematologic neoplasms. Clonal hematopoiesis indeterminate potential (CHIP) represents known factor for malignancy and this study describes the prevalence patterns CHIP mutations across several types solid transplants. Experimental Design: We use two national biobank cohorts comprised >650,000 participants linked genomic longitudinal...
Abstract Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in hematopoietic stem cell that results clonal expansion. These driver mutations can be single nucleotide variants cancer genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors influence variations mCA fitness and ultimately result different expansion rates are not well understood. We used Passenger-Approximated Expansion Rate (PACER) method to estimate...
Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased mortality and malignancy risk, yet the determinants clonal expansion remain poorly understood. We performed sequencing at >4,000x depth coverage for CHIP mutations in 6,986 postmenopausal women from Women’s Health Initiative two timepoints approximately 15 years apart. Among 3,685 detected baseline (VAF ≥ 0.5%), 50% progressed to 2%) follow-up. confirmed that highly dependent on initial clone size...
Eating disorders -including anorexia nervosa (AN), bulimia nervosa, and binge eating disorder-are clinically distinct but exhibit symptom overlap diagnostic crossover. Genomic analyses have mostly examined AN. We conducted the first genomic meta-analysis of behaviour (BE; 39,279 cases, 1,227,436 controls), alongside new AN (24,223 1,243,971 controls) its subtypes (all European ancestries). identified six loci associated with BE, including higher body mass index (BMI) impulse-control...
Abstract With age, acquired mutations can cause clonal expansion of hematopoietic stem cells (HSC). This hematopoiesis indeterminate potential (CHIP) leads to an increased predisposition numerous diseases including blood cancer and cardiovascular disease. Here, we report multi- ancestry genome-wide association meta-analyses CHIP among 323,112 individuals (19.5% non-European; 5.3% have CHIP). We identify 15 significant regions nominate additional loci through multi-trait analyses, highlight...
Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon that occurs when hematopoietic stem cells acquire mutations in select set genes commonly mutated myeloid neoplasia which then expand clonally. Current sequencing assays to detect CHIP are not optimized for the detection these variants and can be cost-prohibitive applied large cohorts or serial sequencing. Here, we present validate targeted assay affordable (∼$8/sample), accurate highly scalable. To...
Not available.
Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued inflammatory gene modifier scan for CHIP-associated CVD among 424,651 UK Biobank participants. CHIP was identified using whole exome sequencing data blood DNA and modeled both as a composite common drivers ( DNMT3A , TET2 ASXL1, JAK2 ) separately. developed predicted expression scores 26 inflammasome-related...
Abstract Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in hematopoietic stem cell that results clonal expansion. These driver mutations can be single nucleotide variants cancer genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors influence variations mCA fitness and ultimately result different expansion rates are not well-understood. We used Passenger-Approximated Expansion Rate (PACER) method to estimate...
<p>Supplementary Figure S10. No evidence for greater transplant complications across the electronic health record lifetime allograft recipients with clonal hematopoiesis of indeterminate potential.</p>
<p>Supplementary Methods</p>
<p>Supplementary Figure S6. CHIP mutation abundance and VAF as a function of time since transplantation for the All Us cohort.</p>
<p>Supplementary Figure S6. CHIP mutation abundance and VAF as a function of time since transplantation for the All Us cohort.</p>
<p>Supplementary Figure S8. Distribution of allograft complications in the UK Biobank.</p>