Retracing Human Genetic Histories and Natural Selection Using Precise Local Ancestry Inference

In an increasingly diverse world, including admixed individuals in genomic studies is imperative for equity and portability. A crucial first step is precise local ancestry inference (LAI). We have developed Orchestra, a LAI model with unprecedented accuracy, and trained on over 10,000 single-origin individuals from 35 worldwide populations. We employed Orchestra to delve into genetic relationships and demographic histories, with a focus on Latin Americans, a prime example of admixture, and the Ashkenazi Jewish, whose origins have long been debated. Finally, Orchestra enabled us to map signatures of selection, notably identifying trace Scandinavian ancestry in British samples and unveiling an immune-rich region linked to respiratory infections. Our work advances the field of LAI and holds promise for improvements in future applications for admixed populations. One-Sentence Summary Orchestra unveils Latino and Ashkenazi ancestral roots and a candidate Viking locus under selection in the British population ### Competing Interest Statement All authors are either employed by and/or hold stock or stock options in Genius Labs. In addition, P.G.Y. has equity in Systomic Health LLC and Ethobiotics LLC. This work has been used to file a provisional patent application. There are no other relevant activities or financial relationships which have influenced this work.