Rosenberg lab at Stanford University

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

  • 2-8-2024 — A new study examines coalescence times, runs of homozygosity, and identity by descent on the X chromosome, predicting the relationship between ROH on the X chromosome and ROH on the autosomes. The study finds that in accord with its mathematical predictions, ROH occupy more of the X chromosome than the autosomes, and the X-chromosomal excess is close to the excess that is predicted.

  • 2-3-2024 — What is the probability distribution of the number of matching alleles between pairs of profiles in a forensic database? This search for matching profiles in an existing database is known as an "Arizona search," after an incident in which such a search was performed in Arizona's database. How does one compute the distribution of the number of matching alleles when actual forensic profiles are unavailable? Egor Lappo introduces a method for evaluating this probability distribution from imputations performed on the basis of neighboring loci in samples typed genome-wide.

  • 1-7-2024Xiran Liu reports Clumppling, a new program for aligning replicate solutions in mixed-membership unsupervised clustering. The approach extends beyond Clumpp and Clumpak, improving computation time and addressing additional scenarios, all while addressing a computational biology problem with ideas from combinatorial optimization and network theory. The method builds on Xiran's earlier mathematical models of the cluster alignment problem [216].

  • 12-15-2023 — If all the games in a single-elimination sports tournament are played sequentially in the same arena, in how many possible sequences can the games be played? Evolutionary biology has the answer. A new study with undergraduate Matt King explores the connections between game sequences in sports tournaments and labeled histories in mathematical phylogenetics, solving new problems that permit simultaneous games across multiple arenas — or simultaneous bifurcations in evolutionary trees. [Stanford Report]

  • 12-10-2023 — The mean allele-sharing dissimilarity between members of a population sometimes exceeds the mean allele-sharing dissimilarity between members of that population and members of a second population. A study led by PhD student Xiran Liu, with help from undergraduates Zarif Ahsan and Tarun Martheswaran, solves for the allele-frequency conditions that generate this counterintuitive phenomenon.

  • 11-16-2023 — How do chess players choose their strategies? Egor Lappo analyzes millions of master-level games from 1971-2019 in the framework of cultural evolution. Modeling the transmission of chess openings from one year's games to the next, he uncovers evidence of that the mechanisms of cultural evolution affect cultural transmission of move choice in chess — mechanisms including success bias, anti-conformity bias, and prestige bias. [Stanford Report]

  • 11-2-2023Jaehee Kim extends the technique of genetic record matching, showing in a new paper that the method can achieve much higher levels of accuracy than in previous analyses [148] [159]. The study considers the case in which links are sought between SNP profiles from low-quality DNA and STR profiles in forensic STR databases, as might occur in certain forensic settings involving trace DNA samples, degraded remains, or ancient DNA.

  • 10-26-2023 — In a new investigation linking mathematical results on population-genetic statistics to diversity statistics in ecology, Maike Morrison investigates how the Shannon entropy statistic for measuring the diversity of ecological communities depends on the abundance of the ith most abundant taxon. The analysis, which considers data from corals and sponge microbiomes, relies on majorization-based inequalities from previous work in the lab [158].

  • 10-24-2023Egor Lappo introduces a new conception of the ancestral configurations that describe the relationship between gene trees and species trees, viewing them through the lattice structure of a partial order. The lattice sturcture can be mined for many results on ancestral configurations, connecting to previous work of Filippo Disanto [152] as well as to work from the lab on labeled histories [212].

  • 9-22-2023 — The unlabeled binary rooted trees can be bijectively associated with the positive integers by a mapping that proceeds recursively from the tree root. Alessandra Maranca shows in a new paper that unlabeled multifurcating rooted trees can also be bijectively associated with the positive integers. The paper provides the bijective construction for two types of multifurcating rooted trees: strictly k-furcating, and at-most-k-furcating

  • 9-17-2023 — Mixed-membership unsupervised clustering is a central part of population-genetic data analysis. A new paper led by Xiran Liu studies misalignment cost for replicate clustering analyses under a Dirichlet model of cluster membership vectors. The paper describes as a function of model parameters the cost for misaligned permutations compared to an optimal permutation. The work assists in understanding properties of the permutations identified by methods like CLUMPP and Clumpak [43] [130].

  • 8-18-2023 — In a new study, Filippo Disanto et al. obtained asymptotic distributions for the total number of ancestral configurations for matching gene trees and species trees, under the Yule and uniform models describing the labeled tree topology. The results extend Filippo's earlier work on ancestral configurations [152] [161], particularly computations focused on asymptotic distributions of root ancestral configurations [211].

  • 7-10-2023Jazlyn Mooney describes a model that examines genealogical lines in an African-American genealogy traced from 1960-1965 back until founding source populations are reached on each branch of the family tree. The model estimates that the mean number of African genealogical lines in a typical genealogy is 314 and the mean number of European genealogical lines is 51. Lily Agranat-Tamir also contributed to the study, which builds on an earlier admixture model papers from the lab [82]. [Genes to Genomes] [Stanford Report]

  • 7-7-2023 — A new study led by postdoc alum Paul Verdu deepens the understanding of the admixture processes taking place on the various islands of Cabo Verde. The study, like an earlier paper combines genetic analysis with linguistic analysis of idiolectal variation in the Kriolu-speaking population. PhD graduate Zach Szpiech contributed to the project.

  • 6-5-2023Danny Cotter reports a study with an updated method for measuring the amount of rare and common variation that is shared across populations. In human data, it provides new calculations and visualizations for the fundamental result that nearly all human genetic variants are either common and widely shared or localized and rare, not common in one place and rare or absent elsewhere.

  • 5-12-2023 — Congratulations to PhD students who have successfully defended their theses!
    • Danny Cotter, "The effects of relatedness and sex-biased demographic processes on human genetic variation"

    • Xiran Liu, "Computational methods and mathematical measures for population relationships"

  • 2-14-2023"All galls are divided into three or more parts" — so reports a study from Shaili Mathur, describing a recursive decomposition used to enumerate labeled histories for galled trees. The study is the first to enumerate labeled histories for a class of phylogenetic network.

  • 12-13-2022 — A new study by Filippo Disanto et al. obtains asymptotic distributions for the number of root ancestral configurations of matching gene trees and species trees, under the Yule and uniform models describing the labeled tree topology. The results build on Filippo's earlier work on ancestral configurations [152] [161].

  • 11-15-2022Egor Lappo has been recognized with honorable mention for the 2023 AMS-MAA-SIAM Frank and Brennie Morgan Prize for Outstanding Research in Mathematics by an Undergraduate Student! Congrats to Egor.

  • 11-15-2022Egor Lappo extends his analysis of coalescent trees by producing new approximate results for expectations and variances of ratios of tree properties under the coalescent model. The results extend Egor's earlier analysis of covariances and correlations of tree properties [198].

  • 9-12-2022 — In the 200th year since Gregor Mendel's birth, a historical commentary discusses Mendel as an icon not only of genetics, but also of the intersection of mathematics and biology.

  • 9-6-2022 — PhD student Maike Morrison, working with former postdoc Nicolas Alcala, introduces a new method for measuring the variability in membership assignments observed in genetic cluster analysis. The method relies on a new and surprising use of the population-genetic statistic FST.

  • 8-29-2022 — PhD student Danny Cotter advances the study of X-chromosomal and autosomal coalescence times in consanguineous populations. Danny shows that coalescence in X-chromosomal first-cousin mating models behaves like the standard coalescent, except with a reduction in coalescence time that depends on the features of consanguinity. The study builds on three recent studies from the lab on coalescence in consanguineous populations [166] [194] [195].

  • 7-11-2022Rohan Mehta and collaborator Mike Steel introduce a general algorithm for computing the probability of reciprocal monophyly of arbitrarily many groups in an arbitrary species tree. The study generalizes earlier computations involving species trees with three and four monophyletic groups [172], and with two monophyletic groups in arbitrary species trees [141].

  • 5-26-2022Xiran Liu and Gili Greenbaum apply the Netstruct hierarchical clustering program to study cultural variation. The analysis, which adapts a method from population genetics for cultural data, reveals new features of variation in regional pronunciation in the eastern United States, folklore motifs and phonemic content of languages worldwide, and US first names.

  • 5-18-2022 — A team including Julia Palacios, Anand Bhaskar, and Filippo Disanto describes an enumeration of binary trees in each of several categories (ranked labeled, ranked unlabeled, unranked labeled, unranked unlabeled) that are compatible with a perfect phylogeny. The enumeration is a contribution to the study of the combinatorics of evolutionary trees.

  • 5-5-2022 — A special issue of Philosophical Transactions of the Royal Society B Biological Sciences with editors Doc Edge, Sohini Ramachandran, and Noah Rosenberg celebrates 50 years since Lewontin's apportionment of human diversity." The special issue covers the background and legacy of this important milestone in the understanding of human genetic variation as well as recent technical advances that connect to it. In the special issue, Nicolas Alcala contributes a study of FST in relation to the frequency of the most frequent allele for multiallelic loci in multiple populations, generalizing earlier results for multiallelic loci in two populations [102] and biallelic loci in multiple populations [149].

  • 3-21-2022Alissa Severson and a collaborative team report a genetic study of ancient burial sites and their continuity with modern members of the Muwekma Ohlone Tribe. The project, a collaboration with the tribal leadership, finds a component of genetic ancestry that connects two burial sites separated by hundreds of years with each other and with the modern tribal members. [Illinois News Bureau] [Stanford Report]

  • 11-30-2021 — Under the coalescent model, a genealogical tree possess a series of features: its height, length, sum of external branches, sum of internal branches, and mean basal branch length. Egor Alimpiev has calculated the covariance and correlation coefficients of all these pairs of random variables, providing a compendium of existing and new fundamental results for the coalescent model. The calculation builds on a previous calculation for one of the pairs considered [154].

  • 11-11-2021 — The Sackin index is one of the most commonly used measures of tree balance. Undergraduate Matt King reports a simple new proof of a result that finds the mean value of the Sackin index across all labeled topologies on n leaves. The proof makes use of an identity that has been called by Graham, Knuth & Patashnik a "remarkable property of the 'middle' elements of Pascal's triangle."

  • 8-24-2021 — For a caterpillar species tree, undergraduate Egor Alimpiev studies coalescent histories in a family of gene trees, the p-pseudocaterpillar gene trees. For this family, his study investigates a claim that the number of coalescent histories is affected by a tradeoff between the number of possible sequences of coalescences and the number of species tree branches on which those sequences can take place. He finds a very nice symmetry. The work extends a study by a previous undergraduate in the lab, Zoe Himwich [176]

  • 8-24-2021 — PhD student Danny Cotter continues the investigation of coalescence times in consanguineous populations, considering the mean time to coalescence for a pair of lineages on the X chromosome in each of four first-cousin mating models. He finds that matrilateral first-cousin mating reduces X-chromosomal coalescence times to a greater extent than patrilateral first-cousin mating. The work builds on two studies led by co-author Alissa Severson [166] [194].

  • 5-28-2021 — In a new article led by PhD student Alissa Severson, the distribution of coalescence times is computed in a diploid model of a consanguineous population. Using a separation-of-time-scales approach, the study shows that the time to the most recent common ancestor for pairs of lineages in separate mating pairs follows a coalescent model with a reduced effective popualtion size. The study builds on a previous theoretical study that examined the mean pairwise coalescence time [166].

  • 5-25-2021 — Congratulations! Alissa Severson has successfully defended her PhD, "The effect of relatedness and population structure on patterns of genomic sharing."

  • 5-21-2021Jaehee Kim, Doc Edge, and Amy Goldberg report a study of the decoupling of a phenotype from admixture levels in an admixed population whose source populations differed in phenotype. As time proceeds, the phenotype of an individual comes to reveal less and less information about the individual's admixture level, particularly if mating occurs randomly in the admixed population. [Stanford Report]

  • 3-11-2021Gili Greenbaum and Jaehee Kim report a population-genetic model of gene drives and their potential to "spill over" from one population to another. In the model, an engineered gene drive is introduced into a target population with the goal of overtaking the extant population. Under what circumstances can the introduced gene drive be prevented from overtaking genotypes in non-target populations? The study finds a narrow set of circumstances.

  • 2-8-2021 — Last year we celebrated the 50th anniversary of the journal Theoretical Population Biology. The anniversary came just as the role for mathematical epidemiology models of COVID-19 began receiving intense attention. A recent editorial discusses the connections between decades of population biology modeling and the COVID-19 pandemic.

  • 2-2-2021 — In a genome scan of rats in New York City, former rotation student Arbel Harpak identifies genes associated with metabolism, diet, the nervous system, and locomotion as possible targets of natural selection. The results add to a growing understanding of adaptation in human-commensal species.

  • 12-18-2020 — Colijn & Plazzotta (2018) introduced a clever new way to associate the unlabeled binary rooted trees with the positive integers. A new paper explores the mathematical properties of the Colijn-Plazzotta enumeration. In particular, the study obtains an upper bound on the sequence providing the smallest Colijn-Plazzotta rank assigned to some tree with n leaves, and an asymptotic equivalence for the sequence providing the largest Colijn-Plazzotta rank assigned to some tree with n leaves.

  • 12-2-2020 — Admixture inflates the genetic diversity of the admixed population above that of the source populations — or does it? Simina Boca and Lucy Huang explore the effect of admixture on heterozygosity, examining when an admixed population has heterozygosity greater than that of source populations. The study also characterizes the level of admixture that gives rise to the greatest heterozygosity for a given set of source population allele frequencies.

  • 11-17-2020 — Studies of phylogenetic tree spaces have often focused on unranked labeled trees (panel C below), unranked unlabeled trees (panel D), or sometimes, ranked labeled trees (panel A). In a new study, Jaehee Kim introduces metrics for calculating distances between ranked unlabeled trees, an understudied type of tree that is useful in tracking pathogen lineages (panel B). The finds shows that the metrics can be used to cluster trees arising from a shared generative model, and to distinguish between those that have arisen by different models.

  • 8-4-2020Alyssa Fortier and Jaehee Kim examine the use of ancestry inference as a step to improve relatedness profiling in forensic genetics. By reducing the potential for misspecification of allele frequencies in likelihood calculations, inference of the genetic ancestry of the forensic sample can avoid a false positive inference of relatedness.

  • 7-29-2020Amy Goldberg and Ananya Rastogi report a study of "Assortative mating by population of origin in a mechanistic model of admixture." This work analyzes a model in which individuals mate assortatively in a setting with two ancestral populations and an admixed populaton. The study builds on several previous models from the lab. [82] [122] [133]

  • 6-11-2020Rohan Mehta reports an article entitled "Modelling anti-vaccine sentiment as a cultural pathogen." The paper describes a coupled contagion: the spread of an anti-vaccine sentiment, and the spread of the disease against which the vaccine protects. The dynamics illustrate how spread of sentiment against a vaccine generates and magnifies outbreaks of the associated disease. [Stanford Report]

  • 5-29-2020 — The long-awaited 50th anniversary special issue of Theoretical Population Biology has been published. The special issue contains commentaries on major research areas developed in TPB, commentaries on historic papers, biograpical commentaries, and research articles — including a study by Ilana Arbisser on FST and the triangle inequality. [Stanford Report]

  • 4-24-2020 — Using a combination of coalescent theory and simulation, Kim et al. study the probability under a birth-death process that species trees lie in the "anomaly zone," the region of the parameter space in which species trees can disagree with the gene tree they are most likely to produce. The work buils on earlier studies of the anomaly zone [30] [47], ranked gene trees [85] [97], and joint simulation of species trees and gene trees [140].

  • 3-20-2020 — A new study examines the mathematical connections between homozygosity and heterozygosity statistics and measures of health care fragmentation in health services research. The study relies on results from related studies in the lab [87] [158].

  • 3-10-2020 — PhD graduate Jonathan Kang reports a new study of five measures of linkage disequilibrium. Jonathan computes mathematical bounds on linkage disequilibrium measures in relation to the allele frequencies at a pair of loci, analyzing the implications of these bounds in human genetic data. The study builds on an earlier analysis of the r2 measure [51].

  • 1-9-2020 — A paper by Zoe Himwich, recent Stanford graduate in mathematics, studies coalescent histories for non-matching caterpillar gene trees and species trees. This study in enumerative combinatorics identifies new connections to the Catalan numbers, Dyck paths, and roadblocked monotonic paths not crossing the diagonal of a square lattice. The paper builds on two earlier studies of coalescent histories for caterpillar-like tree families [111] [142].

  • 12-9-2019Gili Greenbaum introduces a new network-based approach to inference of population structure. The method relies on detection of "communities" in genetic distance matrices and can be used to produce a new way of displaying population structure — a "population structure tree."

  • 12-8-2019 — The work of lab alumnus Brian Donovan is featured on the front page of the New York Times.

  • 11-1-2019Gili Greenbaum reports a study of dynamics of the spatial boundary between Neanderthals and Modern Humans before Modern Humans spread rapidly out of Africa. The question is not "why did Modern Humans replace Neanderthals so quickly?" Rather, Gili asks "why did Modern Humans not replace Neanderthals for so long?" The proposed answer lies in the dynamics of infectious disease. [Haaretz] [Stanford Report]

  • 10-1-2019 — A new study by Rohan Mehta computes probabilities under the coalescent model of reciprocal monophyly for sets of gene lineages from three and four species. The computation extends an earlier computation that permitted only two sets of lineages [141]. The study appears in a special issue of Theoretical Population Biology celebrating Marc Feldman's 75th birthday.

  • 9-23-2019Nicolas Alcala studies the coalescent theory of all possible symmetric migration models involving at most four demes. His paper examines coalescent quantities such as the time to the most recent common ancestor under the models, determining how these quantities relate to network properties such as the mean number of edges per vertex and the density of edges. The study introduces a network perspective for coalescent models — applying it to empirical examples on tigers and birds of genus Sholicola in India. PhD graduate Amy Goldberg also contributed to the project.

  • 9-9-2019 — A new paper led by Rohan Mehta examines the behavior of the FST measure of genetic differentiation on haplotypic data. The study illustrates how incrementing the length of the haplotype window tends to decrease FST — but sometimes increases it. The work is closely related to several of the lab's papers on FST [102] [121] [149] [165]. Check out the video abstract drawn and narrated by co-author Alison Feder.

  • 5-8-2019 — In a collaboration with the Stanford Conservation Program, we have developed a stochastic population occupancy model to examine two decades of occupancy data from the campus populations of the California red-legged frog (Rana draytonii). The model seeks to explain population declines of R. draytonii in campus creeks and suggests conservation management approaches for reversing these declines. The study was led by Nicolas Alcala.

  • 5-2-2019 — A new study led by Alissa Severson examines the relationship between runs of homozygosity and identity-by-descent tracts. The paper determines for a diploid coalescent model the time to the most recent common ancestor, both for two haplotypes in the same individual and for two haplotypes in different individuals. The work provides theory that builds on empirical observations in an earlier study [144].

  • 4-29-2019Nicolas Alcala has a new study of mathematical bounds on three population-genetic statistics: GST', Jost's D, and FST. He shows that for biallelic markers whose mean frequency across a set of populations is fixed, these three statistics achieve their maximal values at the same configuration of allele frequencies across populations. The results extend Nicolas's earlier work on FST bounds as well as that of two other studies from the lab concerning bounds on FST [102] [121].

  • 3-26-2019Filippo Disanto reports a study of the enumeration of compact coalescent histories for matching gene trees and species trees. Compact coalescent histories represent a combinatorial structure that collapses standard coalescent histories into a smaller number of equivalence classes. The study extends the lab's work on enumeration of coalescent histories to a new structure.

  • 3-3-2019 — A new paper discusses challenges of interpreting differences in polygenic scores across populations. The paper builds from the models developed by Ph.D. graduate Doc Edge for analyzing the relationship between the magnitude of genetic and phenotypic differences among populations [129] [132].

  • 1-23-2019 — Two papers from the lab appear in a special issue of Bulletin of Mathematical Biology on Algebraic Methods in Phylogenetics.
    • Jaehee Kim, Filippo Disanto, and Naama Kopelman report a study of the properties of the neighbor-joining algorithm when applied to data from admixed populations. The study shows that tree properties conjectured by Kopelman et al. [99] do not necessarily hold for every distance matrix, but they do hold much more frequently than in a null model without an admixed taxon.

    • Filippo Disanto examines the number of nonequivalent ancestral configurations for matching gene trees and species trees. Nonequivalent ancestral configurations at first appear to be less numerous than ancestral configurations without applying the equivalence relation — studied previously by Filippo [152]. Here, Filippo shows that asymptotic growth for nonequivalent configurations is also exponential.
    This pair of studies extends the lab's work on theory of admixture and combinatorics of evolutionary trees.

  • Past news items


    SELECTED RECENT PUBLICATIONS

    X Liu, NM Kopelman, NA Rosenberg (2023) A Dirichlet model of alignment cost in mixed-membership unsupervised clustering. Journal of Computational and Graphical Statistics 32: 1145-1159. [Abstract] [PDF] [Supplement]

    JA Mooney, L Agranat-Tamir, JK Pritchard, NA Rosenberg (2023) On the number of genealogical ancestors tracing to the source groups of an admixed population. Genetics 224: iyad079. [Abstract] [PDF] [Supplement]

    ML Morrison, N Alcala, NA Rosenberg (2022) FSTruct: an FST-based tool for measuring ancestry variation in inference of population structure. Molecular Ecology Resources 22: 2614-2626. [Abstract] [PDF] [Supplement]

    E Alimpiev, NA Rosenberg (2022) A compendium of covariances and correlation coefficients of coalescent tree properties. Theoretical Population Biology 143: 1-13. [Abstract] [PDF]

    J Kim, MD Edge, A Goldberg, NA Rosenberg (2021) Skin deep: the decoupling of genetic admixture levels from phenotypes that differed between source populations. American Journal of Physical Anthropology 175: 406-421 (2021). [Abstract]

    NA Rosenberg (2021) On the Colijn-Plazzotta numbering scheme for unlabeled binary rooted trees. Discrete Applied Mathematics 291: 88-98. [Abstract] [PDF]

    RS Mehta, NA Rosenberg (2020) Modelling anti-vaccine sentiment as a cultural pathogen. Evolutionary Human Sciences 2: e21. [Abstract] [PDF] [Supplement]

    IM Arbisser, NA Rosenberg (2020) FST and the triangle inequality for biallelic markers. Theoretical Population Biology 133: 117-129. [Abstract]

    NA Rosenberg (2020) Fifty years of Theoretical Population Biology. Theoretical Population Biology 133: 1-12. [Abstract]

    ZM Himwich, NA Rosenberg (2020) Roadblocked monotonic paths and the enumeration of coalescent histories for non-matching caterpillar gene trees and species trees. Advances in Applied Mathematics 113: 101939. [Abstract]

    AL Severson, S Carmi, NA Rosenberg (2019) The effect of consanguinity on between-individual identity-by-descent sharing. Genetics 212: 305-316. [Abstract] [PDF]

    NA Rosenberg, MD Edge, JK Pritchard, MW Feldman (2019) Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences. Evolution, Medicine, and Public Health 2019: 26-34. [Abstract] [PDF]

    NA Rosenberg (2019) Enumeration of lonely pairs of gene trees and species trees by means of antipodal cherries. Advances in Applied Mathematics 102: 1-17. [Abstract] [PDF]

    J Kim, MD Edge, BFB Algee-Hewitt, JZ Li, NA Rosenberg (2018) Statistical detection of relatives typed with disjoint forensic and biomedical loci. Cell 175: 848-858. [Abstract] [PDF] [Supplement]