Unfazed

Unfazed determines the parental gamete of origin for de novo mutations by analyzing paired-end Illumina DNA sequencing reads and variant information from sequenced trios (both parents and offspring).

Key Features:

• Parental-origin inference: Assigns maternal or paternal gamete of origin for de novo mutations in sequenced trios.
• Input data: Operates on paired-end Illumina DNA sequencing reads combined with variant information from trios.
• Read-based phasing: Links phase-informative inherited variants with de novo mutations through read-based phasing.
• Haplotype chaining: Chains sequencing reads into haplotype groups to expand the search space for informative sites.
• Improved accuracy: Uses expanded haplotype-based search to increase the accuracy and success rate of parental origin detection.
• Scalability: Demonstrated ability to determine parent-of-origin for nearly 30,000 de novo variants in under 60 hours.

Scientific Applications:

• Inheritance studies: Determining parental origin of de novo mutations to analyze genetic inheritance patterns in families.
• Genetic disease research: Elucidating mechanisms underlying genetic disorders by identifying the gamete of origin for pathogenic de novo variants.
• Evolutionary biology: Investigating sources of genetic variation and mutation dynamics relevant to evolutionary studies.

Methodology:

Links phase-informative inherited variants with de novo mutations via read-based phasing and chains sequencing reads into haplotype groups to expand the search space for informative sites.