Education & Certifications
Master of Science, Stanford University, STATS-MS (2016)
ScB, Brown University, Applied Mathematics – Biology (2012)
AB, Brown University, Philosophy (Logic and Philosophy of Science) (2012)
Noah Rosenberg, Doctoral (Program)
Choosing Subsamples for Sequencing Studies by Minimizing the Average Distance to the Closest Leaf
2015; 201 (2): 499-511
Imputation of genotypes in a study sample can make use of sequenced or densely genotyped external reference panels consisting of individuals that are not from the study sample. It also can employ internal reference panels, incorporating a subset of individuals from the study sample itself. Internal panels offer an advantage over external panels because they can reduce imputation errors arising from genetic dissimilarity between a population of interest and a second, distinct population from which the external reference panel has been constructed. As the cost of next-generation sequencing decreases, internal reference panel selection is becoming increasingly feasible. However, it is not clear how best to select individuals to include in such panels. We introduce a new method for selecting an internal reference panel--minimizing the average distance to the closest leaf (ADCL)--and compare its performance relative to an earlier algorithm: maximizing phylogenetic diversity (PD). Employing both simulated data and sequences from the 1000 Genomes Project, we show that ADCL provides a significant improvement in imputation accuracy, especially for imputation of sites with low-frequency alleles. This improvement in imputation accuracy is robust to changes in reference panel size, marker density, and length of the imputation target region.
View details for DOI 10.1534/genetics.115.176909
View details for Web of Science ID 000362838500013
View details for PubMedID 26307072
View details for PubMedCentralID PMC4596665
Genetic Diversity and Societally Important Disparities.
2015; 201 (1): 1-12
The magnitude of genetic diversity within human populations varies in a way that reflects the sequence of migrations by which people spread throughout the world. Beyond its use in human evolutionary genetics, worldwide variation in genetic diversity sometimes can interact with social processes to produce differences among populations in their relationship to modern societal problems. We review the consequences of genetic diversity differences in the settings of familial identification in forensic genetic testing, match probabilities in bone marrow transplantation, and representation in genome-wide association studies of disease. In each of these three cases, the contribution of genetic diversity to social differences follows from population-genetic principles. For a fourth setting that is not similarly grounded, we reanalyze with expanded genetic data a report that genetic diversity differences influence global patterns of human economic development, finding no support for the claim. The four examples describe a limit to the importance of genetic diversity for explaining societal differences while illustrating a distinction that certain biologically based scenarios do require consideration of genetic diversity for solving problems to which populations have been differentially predisposed by the unique history of human migrations.
View details for DOI 10.1534/genetics.115.176750
View details for PubMedID 26354973
View details for PubMedCentralID PMC4566256
- Genetic Diversity and Societally Important Disparities. Genetics 2015; 201 (1): 1-12