What is the test-retest reliability of common task-fMRI measures? New empirical evidence and a meta-analysis, bioRxiv, 2019-06-25
AbstractIdentifying brain biomarkers of disease risk is a growing priority in neuroscience. The ability to identify meaningful biomarkers is limited by measurement reliability; unreliable measures are unsuitable for predicting clinical outcomes. Measuring brain activity using task-fMRI is a major focus of biomarker development; however, the reliability of task-fMRI has not been systematically evaluated. We present converging evidence demonstrating poor reliability of task-fMRI measures. First, a meta-analysis of 90 experiments (N=1,008) revealed poor overall reliability (mean ICC=.397). Second, the test-retest reliabilities of activity in a priori regions of interest across 11 common fMRI tasks collected in the context of the Human Connectome Project (N=45) and the Dunedin Study (N=20) were poor (ICCs=.067-.485). Collectively, these findings demonstrate that common task-fMRI measures are not currently suitable for brain biomarker discovery or individual differences research. We review how this state of affairs came to be and highlight avenues for improving task-fMRI reliability.
biorxiv neuroscience 200-500-users 2019The effect of bioRxiv preprints on citations and altmetrics, bioRxiv, 2019-06-23
1.AbstractA potential motivation for scientists to deposit their scientific work as preprints is to enhance its citation or social impact, an effect which has been empirically observed for preprints in physics, astronomy and mathematics deposited to arXiv. In this study we assessed the citation and altmetric advantage of bioRxiv, a preprint server for the biological sciences. We retrieved metadata of all bioRxiv preprints deposited between November 2013 and December 2017, and matched them to articles that were subsequently published in peer-reviewed journals. Citation data from Scopus and altmetric data from <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpAltmetric.com>Altmetric.com<jatsext-link> were used to compare citation and online sharing behaviour of bioRxiv preprints, their related journal articles, and non-deposited articles published in the same journals. We found that bioRxiv-deposited journal articles received a sizeable citation and altmetric advantage over non-deposited articles. Regression analysis reveals that this advantage is not explained by multiple explanatory variables related to the article and its authorship. bioRxiv preprints themselves are being directly cited in journal articles, regardless of whether the preprint has been subsequently published in a journal. bioRxiv preprints are also shared widely on Twitter and in blogs, but remain relatively scarce in mainstream media and Wikipedia articles, in comparison to peer-reviewed journal articles.
biorxiv scientific-communication-and-education 200-500-users 2019Motility induced fracture reveals a ductile to brittle crossover in the epithelial tissues of a simple animal, bioRxiv, 2019-06-20
ABSTRACTAnimals are characterized by their movement, and their tissues are continuously subjected to dynamic force loading while they crawl, walk, run or swim1. Tissue mechanics fundamentally determine the ecological niches that can be endured by a living organism2. While epithelial tissues provide an important barrier function in animals, they are subjected to extreme strains during day to day physiological activities, such as breathing1, feeding3, and defense response4. How-ever, failure or inability to withstand to these extreme strains can result in epithelial fractures5, 6 and associated diseases7, 8. From a materials science perspective, how properties of living cells and their interactions prescribe larger scale tissue rheology and adaptive response in dynamic force landscapes remains an important frontier9. Motivated by pushing tissues to the limits of their integrity, we carry out a multi-modal study of a simple yet highly dynamic organism, the Trichoplax Adhaerens10–12, across four orders of magnitude in length (1 µm to 10 mm), and six orders in time (0.1 sec to 10 hours). We report the discovery of abrupt, bulk epithelial tissue fractures (∼10 sec) induced by the organism’s own motility. Coupled with rapid healing (∼10 min), this discovery accounts for dramatic shape change and physiological asexual division in this early-divergent metazoan. We generalize our understanding of this phenomena by codifying it in a heuristic model, highlighting the fundamental questions underlying the debondingbonding criterion in a soft-active-living material by evoking the concept of an ‘epithelial alloy’. Using a suite of quantitative experimental and numerical techniques, we demonstrate a force-driven ductile to brittle material transition governing the morphodynamics of tissues pushed to the edge of rupture. This work contributes to an important discussion at the core of developmental biology13–17, with important applications to an emerging paradigm in materials and tissue engineering5, 18–20, wound healing and medicine8, 21, 22.
biorxiv biophysics 200-500-users 2019Modular and efficient pre-processing of single-cell RNA-seq, bioRxiv, 2019-06-17
AbstractAnalysis of single-cell RNA-seq data begins with the pre-processing of reads to generate count matrices. We investigate algorithm choices for the challenges of pre-processing, and describe a workflow that balances efficiency and accuracy. Our workflow is based on the kallisto and bustools programs, and is near-optimal in speed and memory. The workflow is modular, and we demonstrate its flexibility by showing how it can be used for RNA velocity analyses.
biorxiv bioinformatics 200-500-users 2019Single-cell mass-spectrometry quantifies the emergence of macrophage heterogeneity, bioRxiv, 2019-06-10
The fate and physiology of individual cells are controlled by protein interactions. Yet, our ability to quantitatively analyze proteins in single cells has remained limited. To overcome this barrier, we developed SCoPE2. It lowers cost and hands-on time by introducing automated and miniaturized sample preparation while substantially increasing quantitative accuracy. These advances enabled us to analyze the emergence of cellular heterogeneity as homogeneous monocytes differentiated into macrophage-like cells in the absence of polarizing cytokines. SCoPE2 quantified over 2,700 proteins in 1,018 single monocytes and macrophages in ten days of instrument time, and the quantified proteins allowed us to discern single cells by cell type. Furthermore, the data uncovered a continuous gradient of proteome states for the macrophage-like cells, suggesting that macrophage heterogeneity may emerge even in the absence of polarizing cytokines. Parallel measurements of transcripts by 10x Genomics scRNA-seq suggest that SCoPE2 samples 20-fold more copies per gene, thus supporting quantification with improved count statistics. Joint analysis of the data indicated that most genes had similar responses at the protein and RNA levels, though the responses of hundreds of genes differed. Our methodology lays the foundation for automated and quantitative single-cell analysis of proteins by mass-spectrometry.
biorxiv systems-biology 200-500-users 2019