Estimation of intrafamilial DNA contamination in family trio genome sequencing using deviation from Mendelian inheritance.
Christopher J YoonSu Yeon KimChang Hyun NamJunehawk LeeJung Woo ParkJihyeob MunSeongyeol ParkSoyoung LeeBoram YiKyoung Il MinBrian WileyKelly L BoltonJeong Ho LeeEunjoon KimHee Jeong YooJong Kwan JunJi Seon ChoiMalachi GriffithMalachi GriffithYoung Seok JuPublished in: Genome research (2022)
With the increasing number of sequencing projects involving families, quality control tools optimized for family genome sequencing are needed. However, accurately quantifying contamination in a DNA mixture is particularly difficult when genetically related family members are the sources. We developed TrioMix, a maximum likelihood estimation (MLE) framework based on Mendel's law of inheritance, to quantify DNA mixture between family members in genome sequencing data of parent-offspring trios. TrioMix can accurately deconvolute any intrafamilial DNA contamination, including parent-offspring, sibling-sibling, parent-parent, and even multiple familial sources. In addition, TrioMix can be applied to detect genomic abnormalities that deviate from Mendelian inheritance patterns, such as uniparental disomy (UPD) and chimerism. A genome-wide depth and variant allele frequency plot generated by TrioMix facilitates tracing the origin of Mendelian inheritance deviations. We showed that TrioMix could accurately deconvolute genomes in both simulated and real data sets.
Keyphrases
- genome wide
- drinking water
- mitochondrial dna
- copy number
- single cell
- circulating tumor
- quality control
- cell free
- risk assessment
- single molecule
- health risk
- dna methylation
- electronic health record
- high fat diet
- human health
- big data
- optical coherence tomography
- gene expression
- quality improvement
- skeletal muscle
- adipose tissue
- artificial intelligence
- acute myeloid leukemia
- data analysis
- allogeneic hematopoietic stem cell transplantation
- drug induced