bluuebunny/crossref_metadata_2025_split huggingface dataset:
scphaser: haplotype inference using single-cell RNA-seq data
Authors: Edsgärd Daniel , Reinius Björn , Sandberg Rickard 
Published: August 2016

Abstract
Summary: Determination of haplotypes is important for modelling the phenotypic consequences of genetic variation in diploid organisms, including cis-regulatory control and compound heterozygosity. We realized that single-cell RNA-seq (scRNA-seq) data are well suited for phasing genetic variants, since both transcriptional bursts and technical bottlenecks cause pronounced allelic fluctuations in individual single cells. Here we present scphaser, an R package that phases alleles at heterozygous variants to reconstruct haplotypes within transcribed regions of the genome using scRNA-seq data. The devised method efficiently and accurately reconstructed the known haplotype for ≥93% of phasable genes in both human and mouse. It also enables phasing of rare and de novo variants and variants far apart within genes, which is hard to attain with population-based computational inference.
Availability and Implementation: scphaser is implemented as an R package. Tutorial and code are available at https://github.com/edsgard/scphaser
Contact: rickard.sandberg@ki.se
Supplementary information: Supplementary data are available at Bioinformatics online.
genipe: an automated genome-wide imputation pipeline with automatic reporting and statistical tools
Authors: Lemieux Perreault Louis-Philippe , Legault Marc-André , Asselin Géraldine , Dubé Marie-Pierre 
Published: August 2016

Summary: Genotype imputation is now commonly performed following genome-wide genotyping experiments. Imputation increases the density of analyzed genotypes in the dataset, enabling fine-mapping across the genome. However, the process of imputation using the most recent publicly available reference datasets can require considerable computation power and the management of hundreds of large intermediate files. We have developed genipe, a complete genome-wide imputation pipeline which includes automatic reporting, imputed data indexing and management, and a suite of statistical tests for imputed data commonly used in genetic epidemiology (Sequence Kernel Association Test, Cox proportional hazards for survival analysis, and linear mixed models for repeated measurements in longitudinal studies).
Availability and Implementation: The genipe package is an open source Python software and is freely available for non-commercial use (CC BY-NC 4.0) at https://github.com/pgxcentre/genipe. Documentation and tutorials are available at http://pgxcentre.github.io/genipe.
Contact: louis-philippe.lemieux.perreault@statgen.org or marie-pierre.dube@statgen.org
Supplementary information: Supplementary data are available at Bioinformatics online.
A novel copy number variants kernel association test with application to autism spectrum disorders studies
Authors: Zhan Xiang , Girirajan Santhosh , Zhao Ni , Wu Michael C. , Ghosh Debashis 
Published: August 2016

Motivation: Copy number variants (CNVs) have been implicated in a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability and schizophrenia. Recent advances in high-throughput genomic technologies have enabled rapid discovery of many genetic variants including CNVs. As a result, there is increasing interest in studying the role of CNVs in the etiology of many complex diseases. Despite the availability of an unprecedented wealth of CNV data, methods for testing association between CNVs and disease-related traits are still under-developed due to the low prevalence and complicated multi-scale features of CNVs.
Results: We propose a novel CNV kernel association test (CKAT) in this paper. To address the low prevalence, CNVs are first grouped into CNV regions (CNVR). Then, taking into account the multi-scale features of CNVs, we first design a single-CNV kernel which summarizes the similarity between two CNVs, and next aggregate the single-CNV kernel to a CNVR kernel which summarizes the similarity between two CNVRs. Finally, association between CNVR and disease-related traits is assessed by comparing the kernel-based similarity with the similarity in the trait using a score test for variance components in a random effect model. We illustrate the proposed CKAT using simulations and show that CKAT is more powerful than existing methods, while always being able to control the type I error. We also apply CKAT to a real dataset examining the association between CNV and autism spectrum disorders, which demonstrates the potential usefulness of the proposed method.
Availability and Implementation: A R package to implement the proposed CKAT method is available at http://works.bepress.com/debashis_ghosh/.
Contacts: xzhan@fhcrc.org or debashis.ghosh@ucdenver.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Metrics for rapid quality control in RNA structure probing experiments
Authors: Choudhary Krishna , Shih Nathan P. , Deng Fei , Ledda Mirko , Li Bo , Aviran Sharon 
Published: August 2016

Motivation: The diverse functionalities of RNA can be attributed to its capacity to form complex and varied structures. The recent proliferation of new structure probing techniques coupled with high-throughput sequencing has helped RNA studies expand in both scope and depth. Despite differences in techniques, most experiments face similar challenges in reproducibility due to the stochastic nature of chemical probing and sequencing. As these protocols expand to transcriptome-wide studies, quality control becomes a more daunting task. General and efficient methodologies are needed to quantify variability and quality in the wide range of current and emerging structure probing experiments.
Results: We develop metrics to rapidly and quantitatively evaluate data quality from structure probing experiments, demonstrating their efficacy on both small synthetic libraries and transcriptome-wide datasets. We use a signal-to-noise ratio concept to evaluate replicate agreement, which has the capacity to identify high-quality data. We also consider and compare two methods to assess variability inherent in probing experiments, which we then utilize to evaluate the coverage adjustments needed to meet desired quality. The developed metrics and tools will be useful in summarizing large-scale datasets and will help standardize quality control in the field.
Availability and Implementation: The data and methods used in this article are freely available at: http://bme.ucdavis.edu/aviranlab/SPEQC_software.
Contact: saviran@ucdavis.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
WebSTAR3D: a web server for RNA 3D structural alignment
Authors: Holzhauser Erwin , Ge Ping , Zhang Shaojie 
Published: August 2016

Summary: The WebSTAR3D web server is a user-friendly online interface for the alignment of RNA 3D structures. The website takes as input two files, each of which can be in either PDB or mmCIF format, containing the desired structures to align, via a PDB code or user upload. In return, the user is presented with a visualization of the aligned structures in Jmol or JSmol, along with the corresponding sequence alignment, and the option to download the nucleotide mapping of the structures and a PDB file containing the aligned, superimposed structures.
Availability and Implementation: The WebSTAR3D is available at http://rna.ucf.edu/WebSTAR3D.
Contact: shzhang@cs.ucf.edu
The ‘business of community development’ and the right to the city: reflections on the neoliberalization processes in urban community development
Authors: Fursova Julia 
Published: August 2016

AbstractThe paper explores emerging contradictions in community development, a subset of non-profit sector, within the context of neoliberalization. I examine non-profit sector as a site that has a potential for articulating counter-hegemonic discourse alternative to neoliberalism. Conversely, non-profit sector itself has been subjected to neoliberal co-optation and restructuring that resulted in restricted autonomy of the sector and decreased capacity to advocate for progressive social change. Drawing on my experience as a community engagement worker in one of Toronto's neighbourhood improvement areas, I problematize community development, posing questions about the role of the non-profit agencies in the production of specific socio-economic configurations that may, albeit inadvertently, support neoliberal discourse. Through an example of local community campaign for increased access to public space and services, I highlight options to enhance counter-hegemonic potential of community development as a critical practice aimed at advancing the commons.
Overcoming the dichotomy: new insights into the genomic diversity of open and isolated European populations
Authors: Anagnostou Paolo , Dominici Valentina , Battaggia Cinzia , Pagani Luca , Vilar Miguel , Wells Spencer , Pettener Davide , Sarno Stefania , Boattini Alessio , Francalacci Paolo , Colonna Vincenza , Vona Giuseppe , Calò Carla , Destro Bisol Giovanni , Tofanelli Sergio 
Published: August 2016

ABSTRACTHuman populations are often dichotomized into “isolated” and “open” using cultural and/or geographical barriers to gene flow as differential criteria. Although widespread, the use of these alternative categories could obscure further heterogeneity due to inter-population differences in effective size, growth rate, and timing or amount of gene flow. We compared intra and interpopulation variation measures combining novel and literature data relative to 87,818 autosomal SNPs in 14 open populations and 10 geographic and/or linguistic European isolates. Patterns of intra-population diversity were found to vary significantly more among isolates, probably due to differential levels of drift and inbreeding. The relatively large effective size estimated for some population isolates challenges the generalized view that they originate from small founding groups. Principal component scores based on measures of intra-population variation of isolated and open populations turned out to be distributed along a sort of continuum, with an area of intersection between the two groups. Patterns of inter-population diversity were even closer, as we were able to detect some differences between population groups only for a few multidimensional scaling dimensions. Therefore, different lines of evidence suggest that dichotomizing human populations into open and isolated fails to capture the actual relations among their genomic features.
Evolution of simple multicellularity increases environmental complexity
Authors: Rebolleda-Gómez María , Ratcliff William C. , Fankhauser Jonathon , Travisano Michael 
Published: August 2016

AbstractMulticellularity—the integration of previously autonomous cells into a new, more complex organism—is one of the major transitions in evolution. Multicellularity changed evolutionary possibilities and facilitated the evolution of increased complexity. Transitions to multicellularity are associated with rapid diversification and increased ecological opportunity but the potential mechanisms are not well understood. In this paper we explore the ecological mechanisms of multicellular diversification during experimental evolution of the brewer’s yeast,Saccharomyces cerevisiae. The evolution from single cells into multicellular clusters modifies the structure of the environment, changing the fluid dynamics and creating novel ecological opportunities. This study demonstrates that even in simple conditions, incipient multicellularity readily changes the environment, facilitating the origin and maintenance of diversity.
Identification of Brain Expression Quantitative Trait Loci Associated with Schizophrenia and Affective Disorders in Normal Brain Tissue
Authors: Bhalala Oneil G. , Nath Artika P. ,   UK Brain Expression Consortium, Inouye Michael , Sibley Christopher R. 
Published: August 2016

AbstractSchizophrenia and the affective disorders, here comprising bipolar disorder and major depressive disorder, are psychiatric illnesses that lead to significant morbidity and mortality worldwide. Whilst understanding of their pathobiology remains limited, large case-control studies have recently identified single nucleotide polymorphisms (SNPs) associated with these disorders. However, discerning the functional effects of these SNPs has been difficult as the associated causal genes are unknown. Here we evaluated whether schizophrenia and affective disorder associated-SNPs are correlated with gene expression within human brain tissue. Specifically, to identify expression quantitative trait loci (eQTLs), we leveraged disorder-associated SNPs identified from six Psychiatric Genomics Consortium and CONVERGE Consortium studies with gene expression levels in post-mortem, neurologically-normal tissue from two independent human brain tissue expression datasets (UK Brain Expression Consortium (UKBEC) and Genotype-Tissue Expression (GTEx)). We identified 6 188 and 16 720 cis-acting SNPs exceeding genome-wide significance (p<5x10−8) in the UKBEC and GTEx datasets, respectively. 1 288 cis-eQTLs were significant in a metaanalysis leveraging overlapping brain regions and were associated with expression of 15 genes, including three non-coding RNAs. One cis-eQTL, rs 16969968, results in a functionally disruptive missense mutation inCHRNA5, a schizophrenia-implicated gene. Meta-analysis identified 297trans-eQTLs associated with 24 genes that were significant in a region-specific manner. Importantly, comparing across tissues, we find that blood eQTLs largely do not capture brain cis-eQTLs. This study identifies putatively causal genes whose expression in region-specific brain tissue may contribute to the risk of schizophrenia and affective disorders.
On the estimation errors ofKMandVfrom time-course experiments using the Michaelis–Menten equation
Authors: Stroberg Wylie , Schnell Santiago 
Published: August 2016

AbstractThe conditions under which the Michaelis–Menten equation accurately captures the steady-state kinetics of a simple enzyme-catalyzed reaction is contrasted with the conditions under which the same equation can be used to estimate parameters,KMandV, from progress curve data. Validity of the underlying assumptions leading to the Michaelis–Menten equation are shown to be necessary, but not sufficient to guarantee accurate estimation ofKMandV. Detailed error analysis and numerical “experiments” show the required experimental conditions for the independent estimation of bothKMandVfrom progress curves. A timescale,tQ, measuring the portion of the time course over which the progress curve exhibits substantial curvature provides a novel criterion for accurate estimation ofKMandVfrom a progress curve experiment. It is found that, if the initial substrate concentration is of the same order of magnitude asKM, the estimated values of theKMandVwill correspond to their true values calculated from the microscopic rate constants of the corresponding mass-action system, only so long as the initial enzyme concentration is less thanKM.
An autonomous meiosis-specific region of yeast Nup2 (hNup50) promotes normal meiotic chromosome dynamics inSaccharomyces cerevisiae
Authors: Chu Daniel B. , Burgess Sean M. 
Published: August 2016

ABSTRACTMeiosis is a specialized cellular program required to create haploid gametes from diploid parent cells. Prior to the first meiotic division, homologous chromosomes pair, synapse, and recombine to ensure their proper disjunction at anaphase I. Additionally, telomeres tethered at the nuclear envelope cluster in the bouquet configuration where they are subjected to dramatic pulling forces acting from outside of the nucleus. InSaccharomyces cerevisiae, the telomere-associated protein Ndj1 is required for bouquet formation. When Ndj1 is absent, these dramatic motions cease and multiple steps of meiosis I prophase progression are delayed. Here we identified Nup2 in a pool of enriched proteins that co-purify with tagged Ndj1 from meiotic cell extracts. Nup2 is a nonessential nucleoporin that functions in nuclear transport, boundary activity, and telomere silencing in mitotically dividing cells. We found that deletion ofNUP2delayed pairing and synapsis during meiosis, and led to decreased spore viability, similar to thendj1Δmutant phenotype. Surprisingly, thenup2Δ ndj1Δdouble mutant failed to segregate chromosomes, even though the meiotic program continued. These results suggest that a physical impediment to nuclear division is created in the absence of Nup2 and Ndj1. Our deletion analysis ofNUP2identified a previously uncharacterized 125-amino acid region that is both necessary and sufficient to complement all ofnup2Δ’s meiotic phenotypes, which we call themeioticautonomousregion (MAR). We propose that Ndj1 and Nup2 function in parallel pathways to promote the dynamic chromosome events of meiotic chromosome dynamics, perhaps through the establishment or maintenance of higher-order chromosome organization.
A damped oscillator imposes temporal order on posterior gap gene expression inDrosophila
Authors: Verd Berta , Clark Erik , Wotton Karl R. , Janssens Hilde , Jiménez-Guri Eva , Crombach Anton , Jaeger Johannes 
Published: August 2016

AbstractInsects determine their body segments in two different ways. Short-germband insects, such as the flour beetleTribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar flyDrosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of theDrosophilasegmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of theDrosophilaembryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. InTribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels inDrosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition, and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects.Author summaryDifferent insect species exhibit one of two distinct modes of determining their body segments during development: they either use a molecular oscillator to position segments sequentially, or they generate segments simultaneously through a hierarchical gene-regulatory cascade. The sequential mode is ancestral, while the simultaneous mode has been derived from it independently several times during evolution. In this paper, we present evidence which suggests that simultaneous segmentation also involves an oscillator in the posterior of the embryo of the vinegar fly,Drosophila melanogaster. This surprising result indicates that both modes of segment determination are much more similar than previously thought. Such similarity provides an important step towards explaining the frequent evolutionary transitions between sequential and simultaneous segmentation.
AN ISOCHORE FRAMEWORK UNDERLIES CHROMATIN ARCHITECTURE
Authors: Jabbari Kamel , Bernardi Giorgio 
Published: August 2016

AbstractA recent investigation showed the existence of correlations between the architectural features of mammalian interphase chromosomes and the compositional properties of isochores. This result prompted us to compare maps of the Topologically Associating Domains (TADs) and of the Lamina Associated Domains (LADs) with the corresponding isochore maps of mouse and human chromosomes. This approach revealed that: 1) TADs and LADs correspond to isochores,i.e.,isochores are the genomic units that underlie chromatin domains; 2) the conservation of TADs and LADs in mammalian genomes is explained by the evolutionary conservation of isochores; 3) chromatin domains corresponding to GC-poor isochores (e.g.,LADs) interact with other domains also corresponding to GC-poor isochores even if located far away on the chromosomes; in contrast, chromatin domains corresponding to GC-rich isochores (e.g.,TADs) show more localized chromosomal interactions, many of which are inter-chromosomal. In conclusion, this investigation establishes a link between DNA sequences and chromatin architecture, explains the evolutionary conservation of TADs and LADs and provides new information on the spatial distribution of GC-poor/gene-poor and GC-rich/gene-rich chromosomal regions in the interphase nucleus.
Fast and accuratede novogenome assembly from long uncorrected reads
Authors: Vaser Robert , Sović Ivan , Nagarajan Niranjan , Šikić Mile 
Published: August 2016

The assembly of long reads from Pacific Biosciences and Oxford Nanopore Technologies typically requires resource intensive error correction and consensus generation steps to obtain high quality assemblies. We show that the error correction step can be omitted and high quality consensus sequences can be generated efficiently with a SIMD accelerated, partial order alignment based stand-alone consensus module called Racon. Based on tests with PacBio and Oxford Nanopore datasets we show that Racon coupled with Miniasm enables consensus genomes with similar or better quality than state-of-the-art methods while being an order of magnitude faster.Racon is available open source under the MIT license athttps://github.com/isovic/racon.git.
Long-time analytic approximation of large stochastic oscillators: simulation, analysis and inference
Authors: Minas Giorgos , Rand David A 
Published: August 2016

AbstractIn order to analyse large complex stochastic dynamical models such as those studied in systems biology there is currently a great need for both analytical tools and also algorithms for accurate and fast simulation and estimation. We present a new stochastic approximation of biological oscillators that addresses these needs. Our method, called phase-corrected LNA (pcLNA) overcomes the main limitations of the standard Linear Noise Approximation (LNA) to remain uniformly accurate for long times, still maintaining the speed and analytically tractability of the LNA. As part of this, we develop analytical expressions for key probability distributions and associated quantities, such as the Fisher Information Matrix and Kullback-Leibler divergence and we introduce a new approach to system-global sensitivity analysis. We also present algorithms for statistical inference and for long-term simulation of oscillating systems that are shown to be as accurate but much faster than leaping algorithms and algorithms for integration of diffusion equations. Stochastic versions of published models of the circadian clock and NF-κB system are used to illustrate our results.