Elephantid genomes reveal the molecular bases of Woolly Mammoth adaptations to the arctic, bioRxiv, 2015-04-24
Woolly mammoths and the living elephants are characterized by major phenotypic differences that allowed them to live in very different environments. To identify the genetic changes that underlie the suite of adaptations in woolly mammoths to life in extreme cold, we sequenced the nuclear genome from three Asian elephants and two woolly mammoths, identified and functionally annotated genetic changes unique to the woolly mammoth lineage. We find that genes with mammoth specific amino acid changes are enriched in functions related to circadian biology, skin and hair development and physiology, lipid metabolism, adipose development and physiology, and temperature sensation. Finally we resurrect and functionally test the mammoth and ancestral elephant TRPV3 gene, which encodes a temperature sensitive transient receptor potential (thermoTRP) channel involved in thermal sensation and hair growth, and show that a single mammoth-specific amino acid substitution in an otherwise highly conserved region of the TRPV3 channel strongly affected its temperature sensitivity. Our results have identified a set of genetic changes that likely played important roles in the adaptation of woolly mammoths to life in the high artic.
biorxiv genomics 0-100-users 2015Fulfilling the promise of Mendelian randomization, bioRxiv, 2015-04-17
Many important questions in medicine involve questions about causality, For example, do low levels of high-density lipoproteins (HDL) cause heart disease? Does high body mass index (BMI) cause type 2 diabetes? Or are these traits simply correlated in the population for other reasons? A popular approach to answering these problems using human genetics is called Mendelian randomization. We discuss the prospects and limitations of this approach, and some ways forward.
biorxiv genetics 0-100-users 2015An evaluation of the accuracy and speed of metagenome analysis tools, bioRxiv, 2015-04-10
Metagenome studies are becoming increasingly widespread, yielding important insights into microbial communities covering diverse environments from terrestrial and aquatic ecosystems to human skin and gut. With the advent of high-throughput sequencing platforms, the use of large scale shotgun sequencing approaches is now commonplace. However, a thorough independent benchmark comparing state-of-the-art metagenome analysis tools is lacking. Here, we present a benchmark where the most widely used tools are tested on complex, realistic data sets. Our results clearly show that the most widely used tools are not necessarily the most accurate, that the most accurate tool is not necessarily the most time consuming, and that there is a high degree of variability between available tools. These findings are important as the conclusions of any metagenomics study are affected by errors in the predicted community composition. Data sets and results are freely available from httpwww.ucbioinformatics.orgmetabenchmark.html
biorxiv bioinformatics 100-200-users 2015Eight thousand years of natural selection in Europe, bioRxiv, 2015-03-15
The arrival of farming in Europe around 8,500 years ago necessitated adaptation to new environments, pathogens, diets, and social organizations. While indirect evidence of adaptation can be detected in patterns of genetic variation in present-day people, ancient DNA makes it possible to witness selection directly by analyzing samples from populations before, during and after adaptation events. Here we report the first genome-wide scan for selection using ancient DNA, capitalizing on the largest genome-wide dataset yet assembled 230 West Eurasians dating to between 6500 and 1000 BCE, including 163 with newly reported data. The new samples include the first genome-wide data from the Anatolian Neolithic culture, who we show were members of the population that was the source of Europe's first farmers, and whose genetic material we extracted by focusing on the DNA-rich petrous bone. We identify genome-wide significant signatures of selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.
biorxiv genetics 100-200-users 2015Tools and best practices for allelic expression analysis, bioRxiv, 2015-03-07
Allelic expression (AE) analysis has become an important tool for integrating genome and transcriptome data to characterize various biological phenomena such as cis-regulatory variation and nonsense-mediated decay. In this paper, we systematically analyze the properties of AE read count data and technical sources of error, such as low-quality or double-counted RNA-seq reads, genotyping errors, allelic mapping bias, and technical covariates due to sample preparation and sequencing, and variation in total read depth. We provide guidelines for correcting and filtering for such errors, and show that the resulting AE data has extremely low technical noise. Finally, we introduce novel software for high-throughput production of AE data from RNA-sequencing data, implemented in the GATK framework. These improved tools and best practices for AE analysis yield higher quality AE data by reducing technical bias. This provides a practical framework for wider adoption of AE analysis by the genomics community.
biorxiv genomics 0-100-users 2015A complete bacterial genome assembled de novo using only nanopore sequencing data, bioRxiv, 2015-02-20
A method for de novo assembly of data from the Oxford Nanopore MinION instrument is presented which is able to reconstruct the sequence of an entire bacterial chromosome in a single contig. Initially, overlaps between nanopore reads are detected. Reads are then subjected to one or more rounds of error correction by a multiple alignment process employing partial order graphs. After correction, reads are assembled using the Celera assembler. Finally, the assembly is polished using signal-level data from the nanopore employing a novel hidden Markov model. We show that this method is able to assemble nanopore reads from Escherichia coli K-12 MG1655 into a single contig of length 4.6Mb permitting a full reconstruction of gene order. The resulting draft assembly has 98.4% nucleotide identity compared to the finished reference genome. After polishing the assembly with our signal-level HMM, the nucleotide identity is improved to 99.4%. We show that MinION sequencing data can be used to reconstruct genomes without the need for a reference sequence or data from other sequencing platforms.
biorxiv bioinformatics 100-200-users 2015