Rosenberg lab

We are a mathematical, theoretical, and computational lab in genetics and evolution. Research in the lab addresses problems in evolutionary biology and human genetics through a combination of mathematical modeling, computer simulations, development of statistical methods, and inference from population-genetic data. Read more...

RECENT NEWS

9-14-2017 — The lab reports a study of consanguinity and runs of homozygosity in Jewish populations. PhD student Jonathan Kang compares runs of homozygosity in contemporary Jewish populations to estimates of consanguinity measured in the 1950s from interviews with mothers in maternity wards. The study finds that the demographic consanguinity rates predict the fraction of the genome that resides in long runs of homozygosity. PhD graduates Amy Goldberg and Doc Edge contributed to the study.

9-8-2017 — Filippo Disanto reports a study of the number of ancestral configurations possessed by matching gene trees and species trees. Ancestral configurations represent a combinatorial structure useful in producing probability formulas for gene trees given species trees, and they are hence connected to coalescent histories. Filippo's work is the latest in his series of combinatorial enumerations of structures that arise in the study of gene trees and species trees [123] [135] [142].

8-21-2017 — A new study from the lab shows that in the admixed population of Cape Verde, genetic admixture is correlated with a measure of linguistic admixture evaluated by tabulating words of Portuguese and African origin in individuals' speech in the Cape Verde Kriolu lnaguage. The analyses suggest a mechanism of cotransmission of genetic and linguistic admixture during the descent of a creole-speaking admixed population. We congratulate lab alumni Paul Verdu*, Ethan Jewett*, and Trevor Pemberton on the study.

8-5-2017 — Olga Kamneva reports a phylogenetic study of 20 worldwide species of strawberries (Fragaria) on the basis of next-generation sequencing data assembled via a bioinformatics pipeline designed specifically for polyploids of mixed ploidy. The study suggests new hypotheses for the diploid progenitors of polyploid species of Fragaria.

7-6-2017 — Nicolas Alcala has obtained mathematical bounds on population-genetic statistic F_ST in the case of a biallelic marker whose mean frequency across a set of populations is fixed. His bounds provide an explanation of a frequently observed dependence of F_ST on the number of populations under consideration. Nicolas's paper expands on two earlier studies from the lab concerning bounds on F_ST [102] [121].

5-30-2017 — Recent PhD graduate Doc Edge reports in a new study that on the basis of correlations between genotypes at neighboring markers, profiles containing nonoverlapping sets of genetic markers can be connected to the same individual. This "record-matching" is demonstrated using genomic and forensic genetic markers, and it has implications for forensic genetics and genomic privacy. Postdoc Bridget Algee-Hewitt and former postdoc Trevor Pemberton contributed to the project. [Stanford Report news story]

5-8-2017 — Congratulations to Amy Goldberg on the defense of her thesis "Mathematical and statistical approaches to elucidate recent human evolutionary history". Amy's thesis considers mechanistic mathematical models of admixture, including the effect of sex-biased admixture on autosomes and on the X chromosome, and the inference from ancient autosomes and X chromosomes of sex-biased migration during prehistoric admixture events in Europe. She also examines the human population size history of South America on the basis of the density and location of archaeological sites. Congratulations Amy!

4-24-2017 — We congratulate Amy Goldberg on receiving the 2017 Sherwood Washburn Prize from the American Association of Physical Anthropologists! This prize recognizes the best student presentation at the AAPA annual meeting. Amy spoke about her work on the contrast between Neolithic and Bronze Age migrations in Europe in their levels of male and female migration. [Read the paper]

3-15-2017 — Amy Goldberg reports that two ancient migration events in Europe involved different proportions of male and female migrants, the earlier Neolithic migration from Anatolia having similar numbers of males and females and the later Pontic-Caspian migration having a greater proportion of males. The result, relying on comparisons of ancient DNA patterns from the X chromosome and the autosomes, builds on Amy's earlier work on sex bias in genetic admixture models [122] [133]. [Science news story]

3-10-2017 — A new simulation study by postdoc alum Olga Kamneva evaluates the behavior of several methods for inferring species networks when the evolutionary process includes hybridization. The paper provides much-needed information on the comparative performance of the various approaches.

2-27-2017 — Postdoc alum Olga Kamneva reports in PLoS Computational Biology a study of the relationship between genome composition of microbes and the co-occurrence of microbes in the environment. She finds that comparisons of microbial genomes can contribute to predictions about whether microbes are associated ecologically. Congrats Olga!

2-22-2017 — We wish several members of the lab well in their new positions.

Nicolas Alcala — Postdoc with Matthieu Foll, International Agency for Research on Cancer, World Health Organization, Lyon.
Filippo Disanto — Junior faculty, Department of Mathematics, University of Pisa (sponsored by the Rita Levi Montalcini researcher program).
Doc Edge — Postdoc with Graham Coop, Department of Evolution and Ecology, University of California, Davis.
Olga Kamneva — Bioinformatics Scientist, Affymetrix, Inc.

11-14-2016 — Postdoc Lawrence Uricchio has reported an upper bound on the size of gene tree sets required before all splits of a species tree appear in a gene tree set with a specified probability. His upper bound depends on a single parameter — the shortest internal branch in the species tree. The computation extends the lab's work on methods for species tree inference from gene trees.

10-14-2016 — Recent PhD graduate Doc Edge has devised a general mathematical model to understand how genotypic differences between populations contribute to phenotypic differences between populations. He uses the model to analyze the relationship of genetics to "health disparities," concluding that health disparities that all trend in the same direction are incompatible with neutral genetic explanations. The work extends a simpler model of Doc's [129], allowing for diploidy, genetic drift, and general distributions of allele frequencies.

10-7-2016 — Postdoc Filippo Disanto continues the lab's work on coalescent histories with a study of the number of coalescent histories for matching gene trees in caterpillar-like families of species trees. Filippo's work solves an open problem from earlier work in the lab [111], showing that the number of coalescent histories is asymptotic to a constant multiple of the Catalan numbers. He uses clever iterative enumerations and techniques of analytic combinatorics to obtain the result. See also [41], [68], and [135] for related work.

7-27-2016 — We are pleased to announce that the software MONOPHYLER is now available. MONOPHYLER computes probabilities that sets of lineages are monophyletic, both for general species trees and for trees of small size. MONOPHYLER is reported by PhD student Rohan Mehta. The software encodes formulas from Rohan's recent Proceedings of the National Academy of Sciences paper.

7-22-2016 — We congratulate PhD student Doc Edge on his thesis defense, "Pick up the pieces: combining information from multiple genetic loci." Doc's thesis examines several problems in the mathematical modeling of the genotype-to-phenotype relationship in structured populations, mathematical properties of the F_st measure of genetic differentiation, and population-genetic aspects of forensic DNA testing and genetic association studies. Doc has been recognized with the Samuel Karlin Prize in Mathematical Biology, awarded by the Department of Biology. Congratulations Doc!

7-19-2016 — PhD student Rohan Mehta reports a computation of the probability that a set of gene lineages on an arbitrary species tree. The work generalizes earlier studies from the lab that considered trees of only two or three species. Rohan illustrates the new formula with an application in maize. The study is a contribution to the Comparative Phylogeography volume of the "In the Light of Evolution" special issue series of Proceedings of the National Academy of Sciences USA.

6-27-2016 — We congratulate biology MS student Brian Donovan on the completion of his PhD in science education "An experimental exploration of how text-based instruction in school biology affects belief in genetic essentialism of race in adolescent populations." Brian defended his PhD in the Graduate School of Education on May 26. He is continuing his studies as a postdoctoral fellow at the Biological Sciences Curriculum Study in Colorado Springs.

6-17-2016 — The lab reports a study examining the predicted distribution of gene tree shape under a birth-death model of species divergence. The work suggests that gene trees are expected to be more imbalanced than species trees, potentially providing part of the explanation for an excess of imbalance observed in inferred phylogenies.

6-15-2016 — Congratulations to Amy Goldberg and Jaehee Kim, who have received fellowships for 2016-2017 from the Stanford Center for Computational, Evolutionary, and Human Genomics!

5-12-2016 — Lab alumnus Mike DeGiorgio reports on the consistency properties of species tree inference methods in a model with ancestral population structure. By introducing a model that includes population subdivision in ancestral species, his paper introduces a new direction for studying consistency in species tree inference. The work is related to several recent papers from the lab on consistency of species tree methods ([85], [88], [89], [97], [109])

4-22-2016 — Several projects from the lab have been in the news:

Reuters story about work by Amy Goldberg on human population size history in South America.
Forensic Magazine story and profile about Bridget Algee-Hewitt and her work in craniometrics.
Forensic Magazine story about work by Bridget Algee-Hewitt, Doc Edge, and Jaehee Kim on ancestry information in the CODIS forensic genetic markers.

4-5-2016 — We congratulate PhD student Amy Goldberg on the publication of her Nature article entitled "Post-invasion demography of prehistoric humans in South America." In this work, Amy and her colleagues use the locations and dates of South American archaeological sites to estimate the time trajectory of the human population size history of the continent. Read the news story here.

4-4-2016 — Lab members Bridget Algee-Hewitt, Doc Edge, and Jaehee Kim report that forensic genetic markers selected for their use in individual identification possess a surprising level of information about genetic ancestry. Moreover, their study finds that a general correlation holds for genetic markers between their information about individual identity and ancestry information. The result makes use of theory from the lab on the connection between measures of genetic diversity and genetic differentiation ([102], [121]).

1-5-2016 — The lab helps celebrate the centennial of the journal Genetics! When PhD student Amy Goldberg develops a model for sex-biased admixture on the X-chromosome, a curious mathematical sequence leads to an unexpected connection deep in the Genetics archive.
Read about the oscillatory functions and coupled recursions encountered in this scholarly adventure — with a surprise appearance of the Fibonacci numbers.

10-7-2015 — PhD student Jonathan Kang has analyzed a new approach for prioritizing individuals for whole-genome sequencing. This approach, based on minimizing a quantity the average distance to the closest leaf, seeks to identify a set of samples that will provide optimal templates for imputing genotypes in additional individuals. He compares the method to an earlier algorithm, also from the lab: maximizing phylogenetic diversity ([108]). Jonathan's article has been selected for Genetics issue highlights.

9-30-2015 — Postdoc Filippo Disanto reports a study of the number of coalescent histories for gene trees and species trees in the lodgepole family. He uses connections with other combinatorial structures from theoretical computer science to derive exact results in the context of a new problem arising from biology. The term "lodgepole" for the tree shape he considers is based on a resemblance to the pattern in which lodgepole pine needles branch off the main twig. The work follows earlier studies from the lab on coalescent histories ([41], [68], [111]).

9-24-2015 — We report an article on detecting selective sweeps using a new statistic, the haplotype allele frequency (HAF) score. This statistic tabulates the frequencies of alleles on a haplotype, and it has distinctive patterns of change during a selective sweep. The approach is related to previous articles from the lab that examined haplotype properties for detecting a deviation from null population-genetic models ([23] [127]).

9-9-2015 — The lab reports two articles in this month's issue of Genetics.

PhD student Amy Goldberg reports a study of the effect of sex-biased admixture on the X chromosome. The study has a number of surprises: (1) The admixture level on the X chromosome is not simply a 2/3-and-1/3 linear combination of female and male parameters. (2) A difference in X chromosomal and autosomal levels of admixture need not imply male bias entering the admixed population from one source and female bias from a second source: the bias can be in the same direction in both source populations, but with different magnitudes. (3) A third surprise involves the appearance of a sequence related to the Fibonacci numbers! The paper follows two previous articles from the lab on mechanistic models of admixture ([82], [122]).
We report a review of three cases in which differences in levels of genetic diversity across populations contribute to population differences in societal variables — related to forensic testing, transplantation matching, and genome-wide association. The study also considers a fourth scenario, performing a reanalysis that contests a claim that within-population genetic diversity has influenced global economic development. PhD student Jonathan Kang contributed to the project. [Genes to Genomes blog post from the Genetics Society of America]

Past news items

SELECTED RECENT PUBLICATIONS

MD Edge, BFB Algee-Hewitt, TJ Pemberton, JZ Li, NA Rosenberg (2017) Linkage disequilibrium matches forensic genetic records to disjoint genomic marker sets. Proceedings of the National Academy of Sciences USA 114: 5671-5676. [Abstract] [PDF] [Supplement]

RS Mehta, D Bryant, NA Rosenberg (2016) The probability of monophyly of a sample of gene lineages on a species tree. Proceedings of the National Academy of Sciences 113: 8002-8009. [Abstract] [PDF] [Supplement] [Software]

F Disanto, NA Rosenberg (2015) Coalescent histories for lodgepole species trees. Journal of Computational Biology 22: 918-929. [Abstract] [PDF]

A Goldberg, NA Rosenberg (2015) Beyond 2/3 and 1/3: the complex signatures of sex-biased admixture on the X chromosome. Genetics 201: 263-279. [Abstract] [PDF]

NA Rosenberg, JTL Kang (2015) Genetic diversity and societally important disparities. Genetics 201: 1-12. [Abstract] [PDF] [Supplement]

M DeGiorgio, J Syring, AJ Eckert, AI Liston, R Cronn, DB Neale, NA Rosenberg (2014) An empirical evaluation of two-stage species tree inference strategies using a multilocus dataset from North American pines. BMC Evolutionary Biology 14: 67. [Abstract] [PDF]

M Jakobsson, MD Edge, NA Rosenberg (2013) The relationship between F_ST and the frequency of the most frequent allele. Genetics 193: 515-528. [Abstract] [PDF]

TJ Pemberton, D Absher, MW Feldman, RM Myers, NA Rosenberg, JZ Li (2012) Genomic patterns of homozygosity in worldwide human populations. American Journal of Human Genetics 91: 275-292. [Abstract] [PDF] [Main Supplement]

S Ramachandran, NA Rosenberg (2011) A test of the influence of continental axes of orientation on patterns of human gene flow. American Journal of Physical Anthropology 146: 515-529. [Abstract] [PDF]

ZA Szpiech, NA Rosenberg (2011) On the size distribution of private microsatellite alleles. Theoretical Population Biology 80: 100-113. [Abstract] [PDF]