Dark Control Towards a Unified Account of Default Mode Function by Markov Decision Processes, bioRxiv, 2017-06-15
AbstractThe default mode network (DMN) is believed to subserve the baseline mental activity in humans. Its highest energy consumption compared to other brain networks and its intimate coupling with conscious awareness are both pointing to an overarching function. Many research streams speak in favor of an evolutionarily adaptive role in envisioning experience to anticipate the future. In the present work, we propose a process model that tries to explain how the DMN may implement continuous evaluation and prediction of the environment to guide behavior. Specifically, we answer the question whether the neurobiological properties of the DMN collectively provide the computational building blocks necessary for a Markov Decision Process. We argue that our formal account of DMN function naturally accommodates as special cases previous interpretations based on (1) predictive coding, (2) semantic associations, and (3) a sentinel role. Moreover, this process model for the neural optimization of complex behavior in the DMN offers parsimonious explanations for recent experimental findings in animals and humans.
biorxiv neuroscience 100-200-users 2017High contiguity Arabidopsis thaliana genome assembly with a single nanopore flow cell, bioRxiv, 2017-06-15
AbstractWhile many evolutionary questions can be answered by short read re-sequencing, presenceabsence polymorphisms of genes andor transposons have been largely ignored in large-scale intraspecific evolutionary studies. To enable the rigorous analysis of such variants, multiple high quality and contiguous genome assemblies are essential. Similarly, while genome assemblies based on short reads have made genomics accessible for non-reference species, these assemblies have limitations due to low contiguity. Long-read sequencers and long-read technologies have ushered in a new era of genome sequencing where the lengths of reads exceed those of most repeats. However, because these technologies are not only costly, but also time and compute intensive, it has been unclear how scalable they are. Here we demonstrate a fast and cost effective reference assembly for an Arabidopsis thaliana accession using the USB-sized Oxford Nanopore MinION sequencer and typical consumer computing hardware (4 Cores, 16Gb RAM). We assemble the accession KBS-Mac-74 into 62 contigs with an N50 length of 12.3 Mb covering 100% (119 Mb) of the non-repetitive genome. We demonstrate that the polished KBS-Mac-74 assembly is highly contiguous with BioNano optical genome maps, and of high per-base quality against a likewise polished Pacific Biosciences long-read assembly. The approach we implemented took a total of four days at a cost of less than 1,000 USD for sequencing consumables including instrument depreciation.
biorxiv genomics 200-500-users 2017An open resource for transdiagnostic research in pediatric mental health and learning disorders, bioRxiv, 2017-06-14
ABSTRACTTechnological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5-21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics, and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n = 664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).
biorxiv neuroscience 100-200-users 2017Beyond Consensus Embracing Heterogeneity in Curated Neuroimaging Meta-Analysis, bioRxiv, 2017-06-14
Coordinate-based meta-analysis can provide important insights into mind-brain relationships. A popular approach for curated small-scale meta-analysis is activation likelihood estimation (ALE), which identifies brain regions consistently activated across a selected set of experiments, such as within a functional domain or mental disorder. ALE can also be utilized in meta-analytic co-activation modeling (MACM) to identify brain regions consistently co-activated with a seed region. Therefore, ALE aims to find consensus across experiments, treating heterogeneity across experiments as noise. However, heterogeneity within an ALE analysis of a functional domain might indicate the presence of functional sub-domains. Similarly, heterogeneity within a MACM analysis might indicate the involvement of a seed region in multiple co-activation patterns that are dependent on task contexts. Here, we demonstrate the use of the author-topic model to automatically determine if heterogeneities within ALE-type meta-analyses can be robustly explained by a small number of latent patterns. In the first application, the author-topic modeling of experiments involving self-generated thought (N = 179) revealed cognitive components fractionating the default network. In the second application, the author-topic model revealed that the left inferior frontal junction (IFJ) participated in multiple task-dependent co-activation patterns (N = 323). Furthermore, the author-topic model estimates compared favorably with spatial independent component analysis in both simulation and real data. Overall, the results suggest that the author-topic model is a flexible tool for exploring heterogeneity in ALE-type meta-analyses that might arise from functional sub-domains, mental disorder subtypes or task-dependent co-activation patterns. Code for this study is publicly available (httpsgithub.comThomasYeoLabCBIGtreemasterstable_projectsmeta-analysisNgo2019_AuthorTopic).
biorxiv neuroscience 0-100-users 2017Epigenetic maintenance of DNA methylation after evolutionary loss of the de novo methyltransferase, bioRxiv, 2017-06-14
ABSTRACTAfter the initial establishment of symmetric cytosine methylation patterns by de novo DNA methyltransferases (DNMTs), maintenance DNMTs mediate epigenetic memory by propagating the initial signal. We find that CG methylation in the yeast Cryptococcus neoformans is dependent on a purely epigenetic mechanism mediated by the single DNMT encoded by the genome, Dnmt5. Purified Dnmt5 is a maintenance methyltransferase that strictly requires a hemimethylated substrate, and methylation lost by removal of Dnmt5 in vivo is not restored by its mitotic or meiotic reintroduction. Phylogenetic analysis reveals that the ancestral species had a second methyltransferase, DnmtX, whose gene was lost between 50 and 150 Mya. Expression of extant DnmtXs in C. neoformans triggers de novo methylation. These data indicate that DNA methylation has been maintained epigenetically by the Dnmt5 system since the ancient loss of the DnmtX de novo enzyme, implying remarkably long-lived epigenetic memory.Single sentence summaryEpigenetic information can be inherited over geological timescales
biorxiv molecular-biology 100-200-users 2017Evolutionary persistence of DNA methylation for millions of years after ancient loss of a de novo methyltransferase, bioRxiv, 2017-06-14
SUMMARYCytosine methylation of DNA is a widespread modification of DNA that plays numerous critical roles, yet has been lost many times in diverse eukaryotic lineages. In the yeast Cryptococcus neoformans, CG methylation occurs in transposon-rich repeats and requires the DNA methyltransferase, Dnmt5. We show that Dnmt5 displays exquisite maintenance-type specificity in vitro and in vivo and utilizes similar in vivo cofactors as the metazoan maintenance methylase Dnmt1. Remarkably, phylogenetic and functional analysis revealed that the ancestral species lost the gene for a de novo methylase, DnmtX, between 50-150 MYA. We examined how methylation has persisted since the ancient loss of DnmtX. Experimental and comparative studies reveal efficient replication of methylation patterns in C. neoformans, rare stochastic methylation loss and gain events, and the action of natural selection. We propose that an epigenome has been propagated for >50 MY through a process analogous to Darwinian evolution of the genome.
biorxiv molecular-biology 200-500-users 2017