bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Communication of Emergency Response Adaptive Randomization Clinical Trials to Potential Participants
Authors: McEvoy Bredan , Haidar David , Tehranisa Jason , Meurer William J. 
Published: December 2016

AbstractIntroductionAcute clinical stroke trials are challenging to communicate to patients and families considering participation. Response adaptive randomization (RAR) is a technique that alters the proportion of trial subjects receiving active treatment, based on the outcomes of previous subjects. We aimed to determine how well interactive videos would improve understanding of a simulated acute stroke trial scenario that incorporated a design with RAR.MethodsWe performed a cross-sectional study of emergency department patients who were without stroke, altered mental status, or critical illness. Subjects viewed a hypothetical stroke and clinical trial scenario. They were randomized into one of four groups with either an RAR or fixed randomization clinical trial design and with either a standard consent video, or an interactive video.Results:We enrolled 720 participants. In the RAR group with interactive video, 128 out of 149 (85.9%) of the subjects were able to correctly identify the allocation method, compared to the 172 out of 285 (61.6%) in the RAR group with the uninterrupted video for an absolute increase of 25.6% (95% Cl 17-33%). The RAR group with interactive video had a higher odds of correct identification of allocation method (O.R. 2.767, 95% Cl [1.011 – 7.570] while controlling for age, sex, ethnicity, education, self-reported understanding of protocol, stroke awareness and agreement to participate in trial.Conclusions:The interactive video increased participant understanding of an RAR design in a simulated stroke scenario. Future research should focus on whether acute trial recruitment can be enhanced using similar techniques.
Updated reference genome sequence and annotation ofMycobacterium bovisAF2122/97
Authors: Malone Kerri M. , Farrell Damien , Stuber Tod P. , Schubert Olga T. , Aebersold Reudi , Robbe-Austerman Suelee , Gordon Stephen V. 
Published: December 2016

AbstractWe report an update to the reference genome of the bovine tuberculosis bacillusMycobacterium bovisAF2122/97 generated using an integrative multi-‘omics approach. Updates include 42 new CDS, 14 modified annotations, 26 SNP corrections, and disclosure that the RD900 locus, previously described as absent from the genome, is in fact present.
Population history of the Sardinian people inferred from whole-genome sequencing
Authors: Chiang Charleston W K , Marcus Joseph H , Sidore Carlo , Al-Asadi Hussein , Zoledziewska Magdalena , Pitzalis Maristella , Busonero Fabio , Maschio Andrea , Pistis Giorgio , Steri Maristella , Angius Andrea , Lohmueller Kirk E , Abecasis Goncalo R , Schlessinger David , Cucca Francesco , Novembre John 
Published: December 2016

AbstractThe population of the Mediterranean island of Sardinia has made important contributions to genome-wide association studies of traits and diseases. The history of the Sardinian population has also been the focus of much research, and in recent ancient DNA (aDNA) studies, Sardinia has provided unique insight into the peopling of Europe and the spread of agriculture. In this study, we analyze whole-genome sequences of 3,514 Sardinians to address hypotheses regarding the founding of Sardinia and its relation to the peopling of Europe, including examining fine-scale substructure, population size history, and signals of admixture. We find the population of the mountainous Gennargentu region shows elevated genetic isolation with higher levels of ancestry associated with mainland Neolithic farmers and depleted ancestry associated with more recent Bronze Age Steppe migrations on the mainland. Notably, the Gennargentu region also has elevated levels of pre-Neolithic hunter-gatherer ancestry and increased affinity to Basque populations. Further, allele sharing with pre-Neolithic and Neolithic mainland populations is larger on the X chromosome compared to the autosome, providing evidence for a sex-biased demographic history in Sardinia. These results give new insight to the demography of ancestral Sardinians and help further the understanding of sharing of disease risk alleles between Sardinia and mainland populations.
Local Discriminant Hyperalignment for multi-subject fMRI data alignment
Authors: Yousefnezhad Muhammad , Zhang Daoqiang 
Published: December 2016

AbstractMultivariate Pattern (MVP) classification can map different cognitive states to the brain tasks. One of the main challenges in MVP analysis is validating the generated results across subjects. However, analyzing multi-subject fMRI data requires accurate functional alignments between neuronal activities of different subjects, which can rapidly increase the performance and robustness of the final results. Hyperalignment (HA) is one of the most effective functional alignment methods, which can be mathematically formulated by the Canonical Correlation Analysis (CCA) methods. Since HA mostly uses the unsupervised CCA techniques, its solution may not be optimized for MVP analysis. By incorporating the idea of Local Discriminant Analysis (LDA) into CCA, this paper proposes Local Discriminant Hyperalignment (LDHA) as a novel supervised HA method, which can provide better functional alignment for MVP analysis. Indeed, the locality is defined based on the stimuli categories in the train-set, where the correlation between all stimuli in the same category will be maximized and the correlation between distinct categories of stimuli approaches to near zero. Experimental studies on multi-subject MVP analysis confirm that the LDHA method achieves superior performance to other state-of-the-art HA algorithms.
Codon based co-occurrence network motifs in human mitochondria
Authors: Shinde Pramod , Sarkar Camellia , Jalan Sarika 
Published: December 2016

AbstractHuman mitochondrial DNA (mtDNA) generates a highly divergent pool of alleles even within species that have dispersed and expanded in size. On top of that codon position bias plays a relative role in prompting population wide sequence based variations. Codon positions are immensely studied as independent evolutionary genetic markers, however co-evolution of codon positions are still largely unexplored. Using 18,411 genome samples, we analyze nucleotide co-occurrences over mitochondrial DNA of human sub-populations covering most of the mtDNA diversity on the earth. Our codon based network motif investigation reveals that codon position is one of the critical factor to form higher order motifs. It is interesting to report a different evolution of Asian genomes than those of the rest which is divulged by motifs in non-coding regions. Most notably, we demonstrate that there are preferences of codon position co-evolution with respect to codon position sensitivity implying the selective role of evolutionary processes on fundamental formation of genetic code in terms of codon bias evolution. These network based findings not only recapitulates the established facts regarding the importance of each codon position in providing codon bias but also highlight their preferential role in resulting correlated mutations. Moreover, codon based nucleotide co-occurrence provides framework to investigate important evolutionary insights into human mitochondrial evolutionary genomics.
Puckered in pioneer neurons coordinates the motor activity of theDrosophilaembryo
Authors: Karkali Katerina , Vernon Samuel W. , Baines Richard A. , Panayotou George , Martín-Blanco Enrique 
Published: December 2016

SUMMARYCentral Nervous System (CNS) organogenesis is a complex process that obeys precise architectural rules. The impact that nervous system architecture may have on its functionality remains, however, relatively unexplored. To clarify this problem, we analyzed the development of the Drosophila embryonic Ventral Nerve Cord (VNC). VNC morphogenesis requires the tight control of Jun kinase (JNK) signaling, exerted in part via a negative feedback loop mediated by the dual specificity phosphatase Puckered, in a subset of pioneer neurons. Here we show that the JNK pathway autonomously regulates neuronal electrophysiological properties without affecting synaptic vesicle transport. Manipulating, during early embryogenesis, JNK signaling activity in pioneer neurons, directly influences their function as ‘organizers’ of VNC architecture and, moreover, uncovers a role in the coordination of the embryonic motor circuitry that is required for hatching. Together, our data reveal critical links, mediated by the control of the JNK signaling cascade by Puckered, between the structural organization of the VNC and its functional optimization.
Recombinant DNA resources for the comparative genomics ofAncylostoma ceylanicum
Authors: Kapulkin Wadim J. , Magalska Adriana , Janecka Ewa , Ciesielski Arkadiusz , Lobocka Malgorzata , Behnke Jerzy M. , Wedrychowicz Halina 
Published: December 2016

AbstractWe describe the construction and initial characterization of genomic resources (a set of recombinant DNA libraries, representing in total over 90,000 independent plasmid clones), originating from the genome of a hamster adapted hookworm,Ancylostoma ceylanicum. First, with the improved methodology, we generated sets of SL1 (5‘-linker - GGTTAATTACCCAAGTTTGAG), and captured cDNAs from two different hookworm developmental stages: pre-infective L3 and parasitic adults. Second, we constructed a small insert (2-10kb) genomic library. Third, we generated a Bacterial Artificial Chromosome library (30-60kb). To evaluate the quality of our libraries we characterized sequence tags on randomly chosen clones and with first pass screening we generated almost a hundred novel hookworm sequence tags. The sequence tags detected two broad classes of genes: i. conserved nematode genes and ii. putative hookworm-specific proteins. Importantly, some of the identified genes encode proteins of general interest including potential targets for hookworm control. Additionally, we identified a syntenic region in the mitochondrial genome, where the gene order is shared between the free-living nematodeC. elegansandA. ceylanicum. Our results validate the use of recombinant DNA resources for comparative genomics of nematodes, including the free-living genetic model organismC. elegansand closely related parasitic species. We discuss the potential and relevance ofAncylostoma ceylanicumdata and resources generated by the recombinant DNA approach.
In vivo magnetic recording of neuronal activity
Authors: Caruso Laure , Wunderle Thomas , Murphy Lewis Christopher , Valadeiro Joao , Trauchessec Vincent , Trejo Rosillo Josué , Pedro Amaral José , Ni Jianguang , Jendritza Patrick , Fermon Claude , Cardoso Susana , Peixeiro Freitas Paulo , Fries Pascal , Pannetier-Lecoeur Myriam 
Published: December 2016

SUMMARYNeuronal activity generates ionic flows and thereby both magnetic fields and electric potential differences, i.e. voltages. Voltage measurements are widely used, but suffer from isolating and smearing properties of tissue between source and sensor, are blind to ionic flow direction, and reflect the difference between two electrodes, complicating interpretation. Magnetic field measurements could overcome these limitations, but have been essentially limited to magnetoencephalography (MEG), using centimeter-sized, helium-cooled extracranial sensors. Here, we report on in vivo magnetic recordings of neuronal activity from visual cortex of cats withmagnetrodes, specially developed needle-shaped probes carrying micron-sized, non-cooled magnetic sensors based on spin electronics. Event-related magnetic fields inside the neuropil were on the order of several nanoteslas, informing MEG source models and efforts for magnetic field measurements through MRI. Though the signal-to-noise ratio is still inferior to electrophysiology, this proof of concept demonstrates the potential to exploit the fundamental advantages of magnetophysiology.HIGHLIGHTSSpin-electronics based probes achieve local magnetic recordings inside the neuropilMagnetic field recordings were performed in vivo, in anesthetized cat visual cortexEvent-related fields (ERFs) to visual stimuli were up to several nanoteslas in sizeERFs could be detected after averaging less than 20 trialsIN BRIEFCaruso et al. report in vivo, intra-cortical recordings of magnetic fields that reflect neuronal activity, using magnetrodes, i.e. micron size magnetic sensors based on spin electronics.
Fast and Stable Signal Deconvolution via Compressible State-Space Models
Authors: Kazemipour Abbas , Liu Ji , Solarana Krystyna , Nagode Daniel A. , Kanold Patrick O. , Wu Min , Babadi Behtash 
Published: December 2016

Abstract–Objective:Common biological measurements are in the form of noisy convolutions of signals of interest with possibly unknown and transient blurring kernels. Examples include EEG and calcium imaging data. Thus, signal deconvolution of these measurements is crucial in understanding the underlying biological processes. The objective of this paper is to develop fast and stable solutions for signal deconvolution from noisy, blurred and undersampled data, where the signals are in the form of discrete events distributed in time and space.Methods: We introduce compressible state-space models as a framework to model and estimate such discrete events. These state-space models admit abrupt changes in the states and have a convergent transition matrix, and are coupled with compressive linear measurements. We consider a dynamic compressive sensing optimization problem and develop a fast solution, using two nested Expectation Maximization algorithms, to jointly estimate the states as well as their transition matrices. Under suitable sparsity assumptions on the dynamics, we prove optimal stability guarantees for the recovery of the states and present a method for the identification of the underlying discrete events with precise confidence bounds.Results: We present simulation studies as well as application to calcium deconvolution and sleep spindle detection, which verify our theoretical results and show significant improvement over existing techniques.Conclusion: Our results show that by explicitly modeling the dynamics of the underlying signals, it is possible to construct signal deconvolution solutions that are scalable, statistically robust, and achieve high temporal resolution.Significance: Our proposed methodology provides a framework for modeling and deconvolution of noisy, blurred, and undersampled measurements in a fast and stable fashion, with potential application to a wide range of biological data.
The Dachsous/Fat/Four-jointed pathway implements axial long-range cell orientation
Authors: Mangione Federica , Martín-Blanco Enrique 
Published: December 2016

SUMMARYDespite a cumulative body of knowledge describing short-range cell interactions in morphogenetic processes, relatively little is known on the mechanism involved in the long-range spatial and temporal coordination of cells to build functional and structurally organized tissues. In particular, the attainment of a functionally optimized epithelia must require directional cues to instruct cell movements and cell orientations throughout the tissue field. InDrosophila,the adult epidermis of the abdominal segments is createdde novoby the replacement of obsolete larval epidermal cells (LECs) by histoblasts (imaginal founder cells). As these proliferate, expand and fuse, they uniformly organize orienting on the surface along the antero-posterior axis. We found that the coordinated, axially oriented changes in shape of histoblasts respond to a dynamic, yet stereotyped redesign of the epithelial field mediated by the Dachsous/Fat/Four-jointed (Ds/Ft/Fj) pathway. The establishment and refinement of the expression gradients of the atypical cadherins Ds and Ft result in their axial polarization across cell interfaces and differential adhesiveness. We suggest that the role of Ds/Ft/Fj in long-range axially oriented planar cell alignment is a general function and that the regulation of the expression of its components would be crucial in the achievement of tissue uniformity in many other morphogenetic models or during tissue repair.
Local genetic correlation gives insights into the shared genetic architecture of complex traits
Authors: Shi Huwenbo , Mancuso Nicholas , Spendlove Sarah , Pasaniuc Bogdan 
Published: December 2016

AbstractAlthough genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions contribute to the genome-wide genetic correlation is currently lacking. Here, we introduceρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach only requires GWAS summary data and makes no distributional assumption on the causal variant effects sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 35 complex traits, and identified 27 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 7 genomic regions that contribute to the genetic correlation of 12 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we leverage the distribution of local genetic correlations across the genome to assign putative direction of causality for 15 pairs of traits.
Simple adjustment of the sequence weight algorithm remarkably enhances PSI-BLAST performance
Authors: Oda Toshiyuki , Lim Kyungtaek , Tomii Kentaro 
Published: December 2016

AbstractPSI-BLAST, an extremely popular tool for sequence similarity search, features the utilization of Position Specific Scoring Matrix (PSSM) constructed from a multiple sequence alignment (MSA). PSSM allows the detection of more distant homologs than a general amino acid substitution matrix does. An accurate estimation of the weights of sequences in an MSA is crucially important for PSSM construction. PSI-BLAST divides a given MSA into multiple blocks, for which sequence weights are calculated. When the block width becomes very narrow, the sequence weight calculation can be difficult.We demonstrate that PSI-BLAST indeed generates a significant fraction of blocks having widths less than 5, thereby degrading the PSI-BLAST performance. We revised the code of PSI-BLAST to prevent the blocks from being narrower than a given minimum block width (MBW). We designate the modified application of PSI-BLAST as PSI-BLASTexB. When MBW is 25, PSI-BLASTexB notably outperforms PSI-BLAST consistently for three independent benchmark sets. The performance boost is even more drastic when an MSA, instead of a sequence, was used as a query.Our results demonstrate that the generation of narrow-width blocks during the sequence weight calculation is a critically important factor that restricts the PSI-BLAST search performance. By preventing narrow blocks, PSI-BLASTexB remarkably upgrades the PSI-BLAST performance.
Genomic determinants of protein abundance variation in colorectal cancer cells
Authors: Roumeliotis Theodoros I. , Williams Steven Paul , Gonçalves Emanuel , Zamanzad Ghavidel Fatemeh , Aben Nanne , Michaut Magali , Schubert Michael , Wright James C. , Yang Mi , Alsinet Clara , Dienstmann Rodrigo , Guinney Justin , Beltrao Pedro , Brazma Alvis , Stegle Oliver , Adams David J. , Wessels Lodewyk , Saez-Rodriguez Julio , McDermott Ultan , Choudhary Jyoti S. 
Published: December 2016

SummaryAssessing the extent to which genomic alterations compromise the integrity of the proteome is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labelling and tribrid mass spectrometry to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the relationships between genomic and proteomic variation. The robust quantification of 12,000 proteins and 27,000 phosphopeptides revealed how protein symbiosis translates to a co-variome which is subjected to a hierarchical order and exposes the collateral effects of somatic mutations on protein complexes. Targeted depletion of key chromatin modifiers confirmed the transmission of variation and the directionality as characteristics of protein interactions. Protein level variation was leveraged to build drug response predictive models towards a better understanding of pharmacoproteomic interactions in colorectal cancer. Overall, we provide a deep integrative view of the molecular structure underlying the variation of colorectal cancer cells.HighlightsThe cancer cell functional “co-variome” is a strong attribute of the proteome.Mutations can have a direct impact on protein levels of chromatin modifiers.Transmission of genomic variation is a characteristic of protein interactions.Pharmacoproteomic models are strong predictors of response to DNA damaging agents.AbbreviationsCOREADColorectal AdenocarcinomaIMACImmobilized Metal ion Affinity ChromatographyROCReceiver Operating CharacteristicAUCArea Under the CurveWGCNAWeighted Correlation Network AnalysisCNACopy Number AlterationSOMSelf-Organizing MapQTLQuantitative Trait LociMSIMicrosatellite InstabilityCPSColorectal Proteomic Subtypes
High-dimensional regression over disease subgroups
Authors: Dondelinger Frank , Mukherjee Sach ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: December 2016

AbstractWe consider high-dimensional regression over subgroups of observations. Our work is motivated by biomedical problems, where disease subtypes, for example, may differ with respect to underlying regression models, but sample sizes at the subgroup-level may be limited. We focus on the case in which subgroup-specific models may be expected to be similar but not necessarily identical. Our approach is to treat subgroups as related problem instances and jointly estimate subgroup-specific regression coefficients. This is done in a penalized framework, combining anℓ1term with an additional term that penalizes differences between subgroup-specific coefficients. This gives solutions that are globally sparse but that allow information-sharing between the subgroups. We present algorithms for estimation and empirical results on simulated data and using Alzheimer’s disease, amyotrophic lateral sclerosis and cancer datasets. These examples demonstrate the gains our approach can offer in terms of prediction and the ability to estimate subgroup-specific sparsity patterns.