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
3-11-2021
— Gili
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.
8-4-2020 — Alyssa 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.
7-29-2020 — Amy
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]
6-11-2020 — Rohan 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 F_{ST} 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 r^{2} 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].
12-9-2019 — Gili
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.
11-1-2019
— Gili
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.
9-23-2019 — Nicolas 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 F_{ST} measure of
genetic differentiation on haplotypic data. The study illustrates how
incrementing the length of the haplotype window tends to
decrease F_{ST} — but sometimes increases it. The
work is closely related to several of the lab's papers
on F_{ST}
[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].
4-29-2019 — Nicolas Alcala has a
new study of
mathematical bounds on three population-genetic
statistics: G_{ST}', Jost's D,
and F_{ST}. 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 F_{ST} bounds as well as that of two
other studies from the lab concerning bounds
on F_{ST}
[102]
[121].
3-26-2019 — Filippo 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
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) F_{ST}
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]
AJ Aw, NA Rosenberg (2018) Bounding measures of
genetic similarity and diversity using majorization. Journal of
Mathematical Biology 77: 711-737.
[Abstract]
[PDF]
IM Arbisser, EM Jewett, NA Rosenberg (2018) On
the joint distribution of tree height and tree length under the
coalescent. Theoretical Population Biology 122: 46-56.
[Abstract]
[PDF]
N Alcala, NA Rosenberg (2017) Mathematical
constraints on F_{ST}: biallelic markers in
arbitrarily many populations.
Genetics 206: 1581-1600.
[Abstract]
[PDF]
[File
S1]
[File
S2]
JTL Kang, A Goldberg, MD Edge, DM Behar, NA
Rosenberg (2016) Consanguinity rates predict long runs of
homozygosity in Jewish populations. Human Heredity 82:
87-102. [Abstract]
[PDF]
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]
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]