Whole genome sequencing and assembly of a Caenorhabditis elegans genome with complex genomic rearrangements using the MinION sequencing device, bioRxiv, 2017-01-09

ABSTRACTAdvances in 3rd generation sequencing have opened new possibilities for ‘benchtop’ whole genome sequencing. The MinION is a portable device that uses nanopore technology and can sequence long DNA molecules. MinION long reads are well suited for sequencing and de novo assembly of complex genomes with large repetitive elements. Long reads also facilitate the identification of complex genomic rearrangements such as those observed in tumor genomes. To assess the feasibility of the de novo assembly of large complex genomes using both MinION and Illumina platforms, we sequenced the genome of a Caenorhabditis elegans strain that contains a complex acetaldehyde-induced rearrangement and a biolistic bombardment-mediated insertion of a GFP containing plasmid. Using ∼5.8 gigabases of MinION sequence data, we were able to assemble a C. elegans genome containing 145 contigs (N50 contig length = 1.22 Mb) that covered >99% of the 100,286,401 bp reference genome. In contrast, using ∼8.04 gigabases of Illumina sequence data, we were able to assemble a C. elegans genome in 38,645 contigs (N50 contig length = ∼26 kb) containing 117 Mb. From the MinION genome assembly we identified the complex structures of both the acetaldehyde-induced mutation and the biolistic-mediated insertion. To date, this is the largest genome to be assembled exclusively from MinION data and is the first demonstration that the long reads of MinION sequencing can be used for whole genome assembly of large (100 Mb) genomes and the elucidation of complex genomic rearrangements.

biorxiv genomics 100-200-users 2017

Neural precursors of deliberate and arbitrary decisions in the study of voluntary action, bioRxiv, 2017-01-02

AbstractThe readiness potential (RP)—a key ERP correlate of upcoming action—is known to precede subjects’ reports of their decision to move. Some view this as evidence against a causal role for consciousness in human decision-making and thus against free-will. Yet those studies focused on arbitrary decisions—purposeless, unreasoned, and without consequences. It remains unknown to what degree the RP generalizes to deliberate, more ecological decisions. We directly compared deliberate and arbitrary decision-making during a $1000-donation task to non-profit organizations. While we found the expected RPs for arbitrary decisions, they were strikingly absent for deliberate ones. Our results and drift-diffusion model are congruent with the RP representing accumulation of noisy, random fluctuations that drive arbitrary—but not deliberate—decisions. They further point to different neural mechanisms underlying deliberate and arbitrary decisions, challenging the generalizability of studies that argue for no causal role for consciousness in decision-making to real-life decisions.Significance StatementThe extent of human free will has been debated for millennia. Previous studies demonstrated that neural precursors of action—especially the readiness potential—precede subjects’ reports of deciding to move. Some viewed this as evidence against free-will. However, these experiments focused on arbitrary decisions—e.g., randomly raising the left or right hand. We directly compared deliberate (actual $1000 donations to NPOs) and arbitrary decisions, and found readiness potentials before arbitrary decisions, but—critically—not before deliberate decisions. This supports the interpretation of readiness potentials as byproducts of accumulation of random fluctuations in arbitrary but not deliberate decisions and points to different neural mechanisms underlying deliberate and arbitrary choice. Hence, it challenges the generalizability of previous results from arbitrary to deliberate decisions.

biorxiv neuroscience 100-200-users 2017

The hippocampus as a predictive map, bioRxiv, 2016-12-29

ABSTRACTA cognitive map has long been the dominant metaphor for hippocampal function, embracing the idea that place cells encode a geometric representation of space. However, evidence for predictive coding, reward sensitivity, and policy dependence in place cells suggests that the representation is not purely spatial. We approach this puzzle from a reinforcement learning perspective what kind of spatial representation is most useful for maximizing future reward? We show that the answer takes the form of a predictive representation. This representation captures many aspects of place cell responses that fall outside the traditional view of a cognitive map. Furthermore, we argue that entorhinal grid cells encode a low-dimensional basis set for the predictive representation, useful for suppressing noise in predictions and extracting multiscale structure for hierarchical planning.

biorxiv neuroscience 100-200-users 2016

When null hypothesis significance testing is unsuitable for research a reassessment, bioRxiv, 2016-12-21

AbstractNull hypothesis significance testing (NHST) has several shortcomings that are likely contributing factors behind the widely debated replication crisis of psychology, cognitive neuroscience and biomedical science in general. We review these shortcomings and suggest that, after about 60 years of negative experience, NHST should no longer be the default, dominant statistical practice of all biomedical and psychological research. Different inferential methods (NHST, likelihood estimation, Bayesian methods, false-discovery rate control) may be most suitable for different types of research questions. Whenever researchers use NHST they should justify its use, and publish pre-study power calculations and effect sizes, including negative findings. Studies should optimally be pre-registered and raw data published. The current statistics lite educational approach for students that has sustained the widespread, spurious use of NHST should be phased out. Instead, we should encourage either more in-depth statistical training of more researchers andor more widespread involvement of professional statisticians in all research.

biorxiv neuroscience 100-200-users 2016

Improved maize reference genome with single molecule technologies, bioRxiv, 2016-12-20

ABSTRACTComplete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation. These resources facilitate elucidation of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions. Here, we report the assembly and annotation of maize, a genetic and agricultural model species, using Single Molecule Real-Time (SMRT) sequencing and high-resolution optical mapping. Relative to the previous reference genome, our assembly features a 52-fold increase in contig length and significant improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed over 130,000 intact transposable elements (TEs), allowing us to identify TE lineage expansions unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by SMRT sequencing. In addition, comparative optical mapping of two other inbreds revealed a prevalence of deletions in the low gene density region and maize lineage-specific genes.

biorxiv genomics 100-200-users 2016

Cell cycle dynamics of chromosomal organisation at single-cell resolution, bioRxiv, 2016-12-16

SummaryChromosomes in proliferating metazoan cells undergo dramatic structural metamorphoses every cell cycle, alternating between a highly condensed mitotic structure facilitating chromosome segregation, and a decondensed interphase structure accommodating transcription, gene silencing and DNA replication. These cyclical structural transformations have been evident under the microscope for over a century, but their molecular-level analysis is still lacking. Here we use single-cell Hi-C to study chromosome conformations in thousands of individual cells, and discover a continuum of cis-interaction profiles that finely position individual cells along the cell cycle. We show that chromosomal compartments, topological domains (TADs), contact insulation and long-range loops, all defined by ensemble Hi-C maps, are governed by distinct cell cycle dynamics. In particular, DNA replication correlates with build-up of compartments and reduction in TAD insulation, while loops are generally stable from G1 through S and G2. Analysing whole genome 3D structural models using haploid cell data, we discover a radial architecture of chromosomal compartments with distinct epigenomic signatures. Our single-cell data creates an essential new paradigm for the re-interpretation of chromosome conformation maps through the prism of the cell cycle.

biorxiv genomics 100-200-users 2016