Speciation genes are more likely to have discordant gene trees, bioRxiv, 2018-01-09

AbstractSpeciation genes are responsible for reproductive isolation between species. By directly participating in the process of speciation, the genealogies of isolating loci have been thought to more faithfully represent species trees. The unique properties of speciation genes may provide valuable evolutionary insights and help determine the true history of species divergence. Here, we formally analyze whether genealogies from loci participating in Dobzhansky-Muller (DM) incompatibilities are more likely to be concordant with the species tree under incomplete lineage sorting (ILS). Individual loci differ stochastically from the true history of divergence with a predictable frequency due to ILS, and these expectations—combined with the DM model of intrinsic reproductive isolation from epistatic interactions—can be used to examine the probability of concordance at isolating loci. Contrary to existing verbal models, we find that reproductively isolating loci that follow the DM model are often more likely to have discordant gene trees. These results are dependent on the pattern of isolation observed between three species, the time between speciation events, and the time since the last speciation event. Results supporting a higher probability of discordance are found for both derived-derived and derived-ancestral DM pairs, and regardless of whether incompatibilities are allowed or prohibited from segregating in the same population. Our overall results suggest that DM loci are unlikely to be especially useful for reconstructing species relationships, even in the presence of gene flow between incipient species, and may in fact be positively misleading.

biorxiv evolutionary-biology 100-200-users 2018

NanoAmpli-Seq A workflow for amplicon sequencing for mixed microbial communities on the nanopore sequencing platform, bioRxiv, 2018-01-08

AbstractBackgroundAmplicon sequencing on Illumina sequencing platforms leverages their deep sequencing and multiplexing capacity, but is limited in genetic resolution due to short read lengths. While Oxford Nanopore or Pacific Biosciences platforms overcome this limitation, their application has been limited due to higher error rates or smaller data output.ResultsIn this study, we introduce an amplicon sequencing workflow, i.e., NanoAmpli-Seq, that builds on Intramolecular-ligated Nanopore Consensus Sequencing (INC-Seq) approach and demonstrate its application for full-length 16S rRNA gene sequencing. NanoAmpli-Seq includes vital improvements to the aforementioned protocol that reduces sample-processing time while significantly improving sequence accuracy. The developed protocol includes chopSeq software for fragmentation and read orientation correction of INC-Seq consensus reads while nanoClust algorithm was designed for read partitioning-based de novo clustering and within cluster consensus calling to obtain full-length 16S rRNA gene sequences.ConclusionsNanoAmpli-Seq accurately estimates the diversity of tested mock communities with average sequence accuracy of 99.5% for 2D and 1D2 sequencing on the nanopore sequencing platform. Nearly all residual errors in NanoAmpli-Seq sequences originate from deletions in homopolymer regions, indicating that homopolymer aware basecalling or error correction may allow for sequencing accuracy comparable to short-read sequencing platforms.

biorxiv microbiology 100-200-users 2018

Genome-wide association study of 1 million people identifies 111 loci for atrial fibrillation, bioRxiv, 2018-01-05

SummaryTo understand the genetic variation underlying atrial fibrillation (AF), the most common cardiac arrhythmia, we performed a genome-wide association study (GWAS) of > 1 million people, including 60,620 AF cases and 970,216 controls. We identified 163 independent risk variants at 111 loci and prioritized 165 candidate genes likely to be involved in AF. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans or mice (MYH6, NKX2-5, PITX2, TBC1D32, TBX5),1,2 or near genes important for striated muscle function and integrity (e.g. MYH7, PKP2, SSPN, SGCA). Experiments in rabbits with heart failure and left atrial dilation identified a heterogeneous distributed molecular switch from MYH6 to MYH7 in the left atrium, which resulted in contractile and functional heterogeneity and may predispose to initiation and maintenance of atrial arrhythmia.

biorxiv genetics 100-200-users 2018

Acoustically Targeted Chemogenetics for Noninvasive Control of Neural Circuits, bioRxiv, 2018-01-02

ABSTRACTNeurological and psychiatric diseases often involve the dysfunction of specific neural circuits in particular regions of the brain. Existing treatments, including drugs and implantable brain stimulators, aim to modulate the activity of these circuits, but are typically not cell type-specific, lack spatial targeting or require invasive procedures. Here, we introduce an approach to modulating neural circuits noninvasively with spatial, cell-type and temporal specificity. This approach, called acoustically targeted chemogenetics, or ATAC, uses transient ultrasonic opening of the blood brain barrier to transduce neurons at specific locations in the brain with virally-encoded engineered G-protein-coupled receptors, which subsequently respond to systemically administered bio-inert compounds to activate or inhibit the activity of these neurons. We demonstrate this concept in mice by using ATAC to noninvasively modify and subsequently activate or inhibit excitatory neurons within the hippocampus, showing that this enables pharmacological control of memory formation. This technology allows a brief, noninvasive procedure to make one or more specific brain regions capable of being selectively modulated using orally bioavailable compounds, thereby overcoming some of the key limitations of conventional brain therapies.

biorxiv neuroscience 100-200-users 2018

Disequilibrium in Gender Ratios among Authors who Contributed Equally, bioRxiv, 2018-01-01

AbstractIn recent decades, the biomedical literature has witnessed an increasing number of authors per article together with a concomitant increase of authors claiming to have contributed equally. In this study, we analyzed over 3000 publications from 1995–2017 claiming equal contributions for authors sharing the first author position for author number, gender, and gender position. The frequency of dual pairings contributing equally was male-male > mixed gender > female-female. For mixed gender pairs males were more often at the first position although the disparity has lessened in the past decade. Among author associations claiming equal contribution and containing three or more individuals, males predominated in both the first position and number of gender exclusive groupings. Our results show a disequilibrium in gender ratios among authors who contributed equally from expected ratios had the ordering been done randomly or alphabetical. Given the importance of the first author position in assigning credit for a publication, the finding of fewer than expected females in associations involving shared contributions raises concerns about women not receiving their fair share of expected credit. The results suggest a need for journals to request clarity on the method used to decide author order among individuals claiming to have made equal contributions to a scientific publication.

biorxiv scientific-communication-and-education 100-200-users 2018

Confidence modulates exploration and exploitation in value-based learning, bioRxiv, 2017-12-29

AbstractUncertainty is ubiquitous in cognitive processing, which is why agents require a precise handle on how to deal with the noise inherent in their mental operations. Previous research suggests that people possess a remarkable ability to track and report uncertainty, often in the form of confidence judgments. Here, we argue that humans use uncertainty inherent in their representations of value beliefs to arbitrate between exploration and exploitation. Such uncertainty is reflected in explicit confidence judgments. Using a novel variant of a multi-armed bandit paradigm, we studied how beliefs were formed and how uncertainty in the encoding of these value beliefs (belief confidence) evolved over time. We found that people used uncertainty to arbitrate between exploration and exploitation, reflected in a higher tendency towards exploration when their confidence in their value representations was low. We furthermore found that value uncertainty can be linked to frameworks of metacognition in decision making in two ways. First, belief confidence drives decision confidence—that is people’s evaluation of their own choices. Second, individuals with higher metacognitive insight into their choices were also better at tracing the uncertainty in their environment. Together, these findings argue that such uncertainty representations play a key role in the context of cognitive control.

biorxiv neuroscience 100-200-users 2017