Biology subjects

Cooper, A.

Publications and source records attributed to Cooper, A..

4 recordsLinked to original sources

bioRxiv2018

Population size history from short genomic scaffolds: how short is too short?

The Pairwise Sequentially Markov Coalescent (PSMC), and its extension PSMC', model past population sizes from a single diploid genome. Both models have been widely applied, even to organisms with scaffold-level genome reference assemblies of limited contiguity. However it is unclear how PSMC and PSMC' perform on short scaffolds. We evaluated psmc and msmc, implementations of the PSMC and PSMC' models respectively, on simulated genomes with low contiguity, and compared results to those from fully contiguous data. Simulations with scaffolds from 100 Mb to 10 kb revealed that psmc maintains high accuracy down to lengths of 100 kb, while msmc is accurate down to 1 Mb. The discrepancy is not due to differing models, but stems from an implementation detail of msmc--homozygous tracts at the ends of scaffolds are discarded, making msmc unreliable for low contiguity genomes. We recommend excluding data that are aligned to shorter scaffolds when undertaking demographic inference.

genetics↗

bioRxiv2018

Biological and cultural drivers of oral microbiota in Medieval and Post-Medieval London, UK

The trillions of microorganisms that live in association with the human body (microbiota) are critical for human health and disease, but there is a limited understanding of how cultural and environmental factors shaped our microbiota diversity through time. However, biomolecular remnants of the human oral microbiota - recovered from the calcified dental plaque (calculus) of our long-dead ancestors - are providing a new means of exploring this key relationship of our evolutionary history. Here, we correlate extensive experimental, archaeological, and biological metadata with 128 ancient dental calculus specimens from Medieval and Post-Medieval London, UK (1066 - 1853 CE). We identify a significant association between microbiota and oral geography (i.e. tooth type and tooth surface), which has confounded ancient microbiota studies to date. By controlling for oral geography, however, we identify the first associations between ancient microbiota and cultural and environmental signatures. We find significant links between ancient British microbiota structure and health, including skeletal markers of stress that may reflect low socioeconomic status. Furthermore, this study provides baseline data to explore factors that drive microbiota differentiation within and between ancient populations and highlights the potential of ancient microbiota to infer detailed health and sociocultural information about the past.

microbiology↗

bioRxiv2018

Dimension Reduction and Visualization for Single-copy Alignments via Generalized PCA

Single-copy sequence alignments have been a valuable source of information for genetic studies; their lack of recombination makes phylogenetic analyses tractable [1]. Specifically, mitochondrial DNA will continue to play an important role in genetic studies due to its high mutation rate and high copy per cell count of the molecule [2]. In this paper we develop a new method for the analysis of single-copy sequence data that simultaneously considers the relationships between sequenced individuals and positions of interest in the genome. We then show that tests for relationships between genetic information and qualitative and quantitative characteristics can be calculated. We motivate the use of our method with examples from empirical data.

bioinformatics↗

bioRxiv2017

T cell activation and the HLA locus associate with latent infections of human African trypanosomiasis

Infections by many pathogens can result in a wide range of phenotypes, from severe to mild, or even asymptomatic. Understanding the genetic basis of these phenotypes can lead to better tools to treat patients or detect reservoirs. To identify human genetic factors that contribute to symptoms diversity, we examined the range of disease severities caused by the parasite T. b. gambiense, the primary cause of human African trypanosomiasis (HAT). We analyzed the transcriptomes of immune cells from both symptomatic HAT cases and individuals with latent infections. Our analysis identified several genes and pathways that associated with the latent phenotype, primarily suggesting increased T and B cell activation in HAT patients relative to latent infections. We also used these transcriptome data to conduct an exome-wide single nucleotide polymorphism (SNP) association study. This suggested that SNPs in the human major histocompatibility locus (HLA) associate with severity, supporting the transcription data and suggesting that T cell activation is a determining factor in outcome. Finally, to establish if T cell activation controls disease severity, we blocked co-stimulatory dependent T cell activation in an animal model for HAT. This showed that reducing T cell activation during trypanosome infection improves symptoms and reduces parasitemia. Our data has used a combination of transcriptome-wide analysis and an in vivo model to reveal that T cell activation and the HLA locus associate with the development of symptoms during HAT. This may open new avenues for the development of new therapeutics and prognostics.

genetics↗