Publications

Ben’s full publication list is available at his Google Scholar profile. Selected publications and abstracts are highlighted below.


Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women. PNAS, 2017.

We conducted a study of PTB compared with term birth in two cohorts of pregnant women: one predominantly Caucasian (n = 39) at low risk for PTB, the second predominantly African American and at high-risk (n = 96)… Previously proposed associations between PTB and lower Lactobacillus and higher Gardnerella abundances replicated in the low-risk cohort, but not in the high-risk cohort. High-resolution bioinformatics enabled taxonomic assignment to the species and subspecies levels, revealing that Lactobacillus crispatus was associated with low risk of PTB in both cohorts, while Lactobacillus iners was not, and that a subspecies clade of Gardnerella vaginalis explained the genus association with PTB…

DADA2: high-resolution sample inference from Illumina amplicon data. Nature Methods, 2016.

We present the open-source software package DADA2 for modeling and correcting Illumina-sequenced amplicon errors (https://github. com/benjjneb/dada2). DADA2 infers sample sequences exactly and resolves differences of as little as 1 nucleotide. In several mock communities, DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants…

Temporal and spatial variation of the human microbiota during pregnancy. PNAS, 2015.

 

Despite the critical role of the human microbiota in health,our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation andmonthly after delivery from the vagina, distal gut, saliva, and tooth/gum…

Rapid evolution of adaptive niche construction in experimental microbial populations. Evolution, 2014

Many species engage in adaptive niche construction: modification of the local environment that increases the modifying organism’s competitive fitness. Adaptive niche construction provides an alternative pathway to higher fitness, shaping the environment rather than conforming to it… Here we report a direct observation of the de novo evolution of adaptive niche construction in populations of the bacteria Pseudomonas fluorescens… We found that adaptive niche construction emerged rapidly, within approximately 100 generations, and became ubiquitous after approximately 400 generations…

Heterozygote advantage as a natural consequence of adaptation in diploids. PNAS, 2011.

Molecular adaptation is typically assumed to proceed by sequential fixation of beneficial mutations. In diploids, this picture presupposes that for most adaptive mutations, the homozygotes have a higher fitness than the heterozygotes. Here, we show that contrary to this expectation, a substantial proportion of adaptive mutations should display heterozygote advantage. This feature of adaptation in diploids emerges naturally from the primary importance of the fitness of heterozygotes for the invasion of new adaptive mutations. We formalize this result in the framework of Fisher’s influential geometric model of adaptation…

Correlated evolution of nearby residues in Drosophilid proteins. PLoS Genetics, 2011.

Here we investigate the correlations between coding sequence substitutions as a function of their separation along the protein sequence… We find that amino acid substitutions are “clustered” along the protein sequence, that is, the frequency of additional substitutions is strongly enhanced within ≈10 residues of a first such substitution. No such clustering is observed for synonymous substitutions, supporting a “correlation length” associated with selection on proteins as the causative mechanism. Clustering is stronger between substitutions that arose in the same lineage than it is between substitutions that arose in different lineages. We consider several possible origins of clustering, concluding that epistasis (interactions between amino acids within a protein that affect function) and positional heterogeneity in the strength of purifying selection are primarily responsible…