Biology subjects

Neher, R. A.

Publications and source records attributed to Neher, R. A..

6 recordsLinked to original sources

bioRxiv2018

Efficient estimation of evolutionary rates by covariance aware regression

Shared ancestry among individuals results in correlated traits and these dependencies need to be accounted for in probabilistic inference. In strictly asexual populations, the covariances have a particularly simple block-like structure imposed by the phylogenetic tree. Ho and Ane showed how this block-like structure can be exploited to efficiently invert covariance matrices and fit linear models on trees in linear time. In this short note, I use these methods to estimate evolutionary rates and to find the root of the tree that optimizes the time-divergence relationship. The algorithm is implemented in TreeTime and can be used to estimate evolutionary rates and their confidence intervals with computational cost scaling linearly in the number of tips.

evolutionary biology↗

bioRxiv2018

Arabidopsis thaliana populations support long-term maintenance and parallel expansions of related Pseudomonas pathogens

Crop disease outbreaks are often associated with clonal expansions of single pathogenic lineages. To determine whether similar boom-and-bust scenarios hold for wild plant pathogens, we carried out a multi-year multi-site survey of Pseudomonas in the natural host Arabidopsis thaliana. The most common Pseudomonas lineage corresponded to a pathogenic clade present in all sites. Sequencing of 1,524 Pseudomonas genomes revealed this lineage to have diversified approximately 300,000 years ago, containing dozens of genetically distinct pathogenic sublineages. These sublineages have expanded in parallel within the same populations and are differentiated both at the level of gene content and disease phenotype. Such coexistence of diverse sublineages indicates that in contrast to crop systems, no single strain has been able to overtake these A. thaliana populations in the recent past. Our results suggest that the selective pressures acting on a plant pathogen in wild hosts may be more complex than those in agricultural systems.

microbiology↗

bioRxiv2017

Nextstrain: real-time tracking of pathogen evolution

SummaryUnderstanding the spread and evolution of pathogens is important for effective public health measures and surveillance. Nextstrain consists of a database of viral genomes, a bioinformatics pipeline for phylodynamics analysis, and an interactive visualisation platform. Together these present a real-time view into the evolution and spread of a range of viral pathogens of high public health importance. The visualization integrates sequence data with other data types such as geographic information, serology, or host species. Nextstrain compiles our current understanding into a single accessible location, publicly available for use by health professionals, epidemiologists, virologists and the public alike.\n\nAvailability and implementationAll code (predominantly JavaScript and Python) is freely available from github.com/nextstrain and the web-application is available at nextstrain.org.

evolutionary biology↗

bioRxiv2017

Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death

HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmission which involves multiple virions per cell could lead to increased numbers of live infected cells if the number of viral DNA copies remains above one after inhibition, as eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high.

bioinformatics↗

bioRxiv2017

Seasonal influenza circulation patterns and projections for 2017-2018

This is not meant as a comprehensive report of recent influenza evolution, but is instead intended as particular observations that may be of relevance. Please also note that observed patterns reflect the GISAID database and may not be entirely representative of underlying dynamics. All analyses are based on the nextflu pipeline [1] with continual updates posted to nextflu.org. We arrive at the following results:\n\nH3N2In H3N2, clade 3c2.a has continued to diversify genetically with complicated and rapid dynamics of different subclades. This diversification is not reflected in serological data that shows only minor to moderate antigenic evolution. Nevertheless, the highly parallel mutation patterns and the rapid rise and fall of clades suggests competitive dynamics of phenotypically distinct viruses.\n\nH1N1pdmVery few H1N1pdm viruses have been observed in recent months. The dominant clade continues to be 6b.1 and there is little amino acid sequence variation within HA. The only notable subclade that has been growing recently is the clade bearing HA1:R205K/S183P. This clade is dominated by North American viruses and we see no evidence that this clade has a particular competitive advantage.\n\nB/VicClade 1A has continued to dominate and mutation 117V has all but taken over the global population. The rise of this mutation was fairly gradual and we have no evidence that it is associated with antigenic change or other benefit to the virus.\n\nB/YamClade 3 has continued to dominate. Within clade 3, a clade with mutation HA1:251V is globally at frequency of about 80% throughout 2016. Within this clade, mutation 211R is at 25% frequency. In addition, a clade without prominent amino acid mutations has been rising throughout 2016.

evolutionary biology↗

bioRxiv2016

Rapid and consistent evolution of colistin resistance in Pseudomonas aeruginosa during morbidostat culture

Colistin is a last resort antibiotic commonly used against multidrug-resistant strains of Pseudomonas aeruginosa. To investigate the potential for in-situ evolution of resistance against colistin and map the molecular targets of colistin resistance, we exposed two P. aeruginosa isolates to colistin using a continuous culture device known as morbidostat. Colistin resistance emerged within two weeks along with highly stereotypic yet strain specific mutation patterns. The majority of mutations hit the prmAB two component signaling system and genes involved in lipopolysaccharide synthesis, including lpxC, pmrE, and migA. In seven out of 18 cultures, we observed mutations in mutS along with a mutator phenotype that seemed to facilitate resistance evolution.

microbiology↗