bluuebunny/crossref_metadata_2025 huggingface dataset:
Computed Tomography–Guided Methylene Blue Labeling Prior to Thoracoscopic Resection of Small Deeply Placed Pulmonary Nodules. Do We Really Need Palpation?
Authors: Demiröz S. , Apaydın Selma , Ertürk Hakan , Biri Suzan , Incekara Funda , Aydogdu Koray , Kaya Sadi , Findik Gokturk
Published: January 2017

Background Video-assisted thoracic surgery (VATS) is widely used for thoracic surgery operations, and day by day it becomes routine for the excision of undetermined pulmonary nodules. However, it is sometimes hard to reach millimetric nodules through a VATS incision. Therefore, some additional techniques were developed to reach such nodules little in size and which are settled on a challenging localization. In the literature, coils, hook wires, methylene blue, lipidol, and barium staining, and also ultrasound guidance were described for this aim. Herein we discuss our experience with CT-guided methylene blue labeling of small, deeply located pulmonary nodules just before VATS excision.

Method From April 2013 to October 2016, 11 patients with millimetric pulmonary nodules (average 8, 7 mm) were evaluated in our clinic. For all these patients who had strong predisposing factors for malignancy, an 18F-FDG PET-CT scan was also performed. The patients whose nodules were decided to be excised were consulted the radiology clinic. The favorable patients were taken to CT room 2 hours prior to the operation, and CT-guided methylene blue staining were performed under sterile conditions.

Results Mean nodule size of 11 patients was 8.7 mm (6, 2–12). Mean distance from the visceral pleural surface was 12.7 mm (4–29.3). Four of the nodules were located on the left (2 upper lobes, 2 lower lobes), and seven of them were on the right (four lower lobes, two upper lobes, one middle lobe). The maximum standardized uptake values (SUV max) on 18F-FDG PET/CT scan ranged between 0 and 2, 79.

Conclusion CT-guided methylene blue staining of millimetric deeply located pulmonary nodules is a safe and feasible technique that helps surgeon find these undetermined nodules by VATS technique without any need of digital palpation.
Mitochondrial protein interactome elucidated by chemical cross-linking mass spectrometry
Authors: Schweppe Devin K. , Chavez Juan D. , Lee Chi Fung , Caudal Arianne , Kruse Shane E. , Stuppard Rudy , Marcinek David J. , Shadel Gerald S. , Tian Rong , Bruce James E.
Published: January 2017

Significance

Mitochondria meet the majority of living cells’ demand for ATP and, as important regulators of redox homeostasis, metabolite levels, and calcium buffering, are a critical link between cell energetics and signaling. Disruption of these processes can induce adaptive or pathological signaling responses to stress and under severe stress promote cell death. Mitochondria have a complex proteome with conformations and interactions that are not well understood. Mitochondrial dysfunction is a direct cause of rare inherited diseases and is implicated in common metabolic diseases and age-related pathology. This study illuminates protein interactions and conformational features of nearly one-third of the mitochondrial proteome. Network information on this scale will enable groundbreaking insights into mitochondrial function, dysfunction, and potential therapeutic targets for mitochondrial-based pathology.
Control of DEMETER DNA demethylase gene transcription in male and female gamete companion cells inArabidopsis thaliana
Authors: Park Jin-Sup , Frost Jennifer M. , Park Kyunghyuk , Ohr Hyonhwa , Park Guen Tae , Kim Seohyun , Eom Hyunjoo , Lee Ilha , Brooks Janie S. , Fischer Robert L. , Choi Yeonhee
Published: January 2017

Significance

TheArabidopsisDEMETER (DME) DNA demethylase is required for reproduction and endosperm gene imprinting. We investigated mechanisms that restrict DME transcription to the female and male companion cells, the central and vegetative cells, adjacent to egg and sperm cells, respectively. We delineated a region, surprisingly within theDMEgene, sufficient for proper DME expression, which rescues seed abortion and aberrant endosperm DNA methylation associated withdmemutations. We discovered overlapping DNA enhancers promoting vegetative and central cell expression, which can be used to pinpoint candidate transcription factors that regulate DME in companion cells. These results show how reproductive DNA demethylation is restricted to companion cells, thereby protecting egg and sperm cells from deleterious DNA demethylation that would be transmitted to progeny.
Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library
Authors: Ahn Seungkirl , Kahsai Alem W. , Pani Biswaranjan , Wang Qin-Ting , Zhao Shuai , Wall Alissa L. , Strachan Ryan T. , Staus Dean P. , Wingler Laura M. , Sun Lillian D. , Sinnaeve Justine , Choi Minjung , Cho Ted , Xu Thomas T. , Hansen Gwenn M. , Burnett Michael B. , Lamerdin Jane E. , Bassoni Daniel L. , Gavino Bryant J. , Husemoen Gitte , Olsen Eva K. , Franch Thomas , Costanzi Stefano , Chen Xin , Lefkowitz Robert J.
Published: January 2017

Significance

The present study reports the discovery of a small-molecule negative allosteric modulator for the β
2
-adrenergic receptor (β
2
AR) via in vitro affinity-based iterative selection of highly diverse DNA-encoded small-molecule libraries. Characterization of the compound demonstrates its selectivity for the β
2
AR and that it negatively modulates a wide range of receptor functions. More importantly, our findings establish a generally applicable, proof-of-concept strategy for screening DNA-encoded small-molecule libraries against purified G-protein–coupled receptors (GPCRs), which holds great potential for discovering therapeutic molecules.
The JWS online simulation database
Authors: Peters Martin , Eicher Johann J , van Niekerk David D , Waltemath Dagmar , Snoep Jacky L
Published: January 2017

JWS Online is a web-based platform for construction, simulation and exchange of models in standard formats. We have extended the platform with a database for curated simulation experiments that can be accessed directly via a URL, allowing one-click reproduction of published results. Users can modify the simulation experiments and export them in standard formats. The Simulation database thus lowers the bar on exploring computational models, helps users create valid simulation descriptions and improves the reproducibility of published simulation experiments.

Availability and Implementation

The Simulation Database is available on line at https://jjj.bio.vu.nl/models/experiments/.
Evolutionary design of multiple genes encoding the same protein
Authors: Terai Goro , Kamegai Satoshi , Taneda Akito , Asai Kiyoshi
Published: January 2017

Motivation

Enhancing expression levels of a target protein is an important goal in synthetic biology. A widely used strategy is to integrate multiple copies of genes encoding a target protein into a host organism genome. Integrating highly similar sequences, however, can induce homologous recombination between them, resulting in the ultimate reduction of the number of integrated genes.

Results

We propose a method for designing multiple protein-coding sequences (i.e. CDSs) that are unlikely to induce homologous recombination, while encoding the same protein. The method, which is based on multi-objective genetic algorithm, is intended to design a set of CDSs whose nucleotide sequences are as different as possible and whose codon usage frequencies are as highly adapted as possible to the host organism. We show that our method not only successfully designs a set of intended CDSs, but also provides insight into the trade-off between nucleotide differences among gene copies and codon usage frequencies.

Availability and Implementation

Our method, named Tandem Designer, is available as a web-based application at http://tandem.trahed.jp/tandem/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Unrealistic phylogenetic trees may improve phylogenetic footprinting
Authors: Nettling Martin , Treutler Hendrik , Cerquides Jesus , Grosse Ivo
Published: January 2017

Motivation

The computational investigation of DNA binding motifs from binding sites is one of the classic tasks in bioinformatics and a prerequisite for understanding gene regulation as a whole. Due to the development of sequencing technologies and the increasing number of available genomes, approaches based on phylogenetic footprinting become increasingly attractive. Phylogenetic footprinting requires phylogenetic trees with attached substitution probabilities for quantifying the evolution of binding sites, but these trees and substitution probabilities are typically not known and cannot be estimated easily.

Results

Here, we investigate the influence of phylogenetic trees with different substitution probabilities on the classification performance of phylogenetic footprinting using synthetic and real data. For synthetic data we find that the classification performance is highest when the substitution probability used for phylogenetic footprinting is similar to that used for data generation. For real data, however, we typically find that the classification performance of phylogenetic footprinting surprisingly increases with increasing substitution probabilities and is often highest for unrealistically high substitution probabilities close to one. This finding suggests that choosing realistic model assumptions might not always yield optimal predictions in general and that choosing unrealistically high substitution probabilities close to one might actually improve the classification performance of phylogenetic footprinting.

Availability and Implementation

The proposed PF is implemented in JAVA and can be downloaded from https://github.com/mgledi/PhyFoo

Supplementary information

Supplementary data are available at Bioinformatics online.
MetaShot: an accurate workflow for taxon classification of host-associated microbiome from shotgun metagenomic data
Authors: Fosso B , Santamaria M , D’Antonio M , Lovero D , Corrado G , Vizza E , Passaro N , Garbuglia A R , Capobianchi M R , Crescenzi M , Valiente G , Pesole G
Published: January 2017

Shotgun metagenomics by high-throughput sequencing may allow deep and accurate characterization of host-associated total microbiomes, including bacteria, viruses, protists and fungi. However, the analysis of such sequencing data is still extremely challenging in terms of both overall accuracy and computational efficiency, and current methodologies show substantial variability in misclassification rate and resolution at lower taxonomic ranks or are limited to specific life domains (e.g. only bacteria). We present here MetaShot, a workflow for assessing the total microbiome composition from host-associated shotgun sequence data, and show its overall optimal accuracy performance by analyzing both simulated and real datasets.

Availability and Implementation

https://github.com/bfosso/MetaShot

Supplementary information

Supplementary data are available at Bioinformatics online.
Ligandbook: an online repository for small and drug-like molecule force field parameters
Authors: Domański Jan , Beckstein Oliver , Iorga Bogdan I
Published: January 2017

Ligandbook is a public database and archive for force field parameters of small and drug-like molecules. It is a repository for parameter sets that are part of published work but are not easily available to the community otherwise. Parameter sets can be downloaded and immediately used in molecular dynamics simulations. The sets of parameters are versioned with full histories and carry unique identifiers to facilitate reproducible research. Text-based search on rich metadata and chemical substructure search allow precise identification of desired compounds or functional groups. Ligandbook enables the rapid set up of reproducible molecular dynamics simulations of ligands and protein-ligand complexes.

Availability and Implementation

Ligandbook is available online at https://ligandbook.org and supports all modern browsers. Parameters can be searched and downloaded without registration, including access through a programmatic RESTful API. Deposition of files requires free user registration. Ligandbook is implemented in the PHP Symfony2 framework with TCL scripts using the CACTVS toolkit.

Supplementary information

Supplementary data are available at Bioinformatics online.
H(O)TA: estimation of DNA methylation and hydroxylation levels and efficiencies from time course data
Authors: Kyriakopoulos Charalampos , Giehr Pascal , Wolf Verena
Published: January 2017

Motivation

Methylation and hydroxylation of cytosines to form 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) belong to the most important epigenetic modifications and their vital role in the regulation of gene expression has been widely recognized. Recent experimental techniques allow to infer methylation and hydroxylation levels at CpG dinucleotides but require a sophisticated statistical analysis to achieve accurate estimates.

Results

We present H(O)TA, a software tool based on a stochastic modeling approach, which simultaneously analyzes time course data from hairpin bisulfite sequencing and hairpin oxidative bisulfite sequencing.

Availability and Implementation

https://mosi.uni-saarland.de/HOTA
Identification of protein complexes by integrating multiple alignment of protein interaction networks
Authors: Ma Cheng-Yu , Chen Yi-Ping Phoebe , Berger Bonnie , Liao Chung-Shou
Published: January 2017

Motivation

Protein complexes are one of the keys to studying the behavior of a cell system. Many biological functions are carried out by protein complexes. During the past decade, the main strategy used to identify protein complexes from high-throughput network data has been to extract near-cliques or highly dense subgraphs from a single protein–protein interaction (PPI) network. Although experimental PPI data have increased significantly over recent years, most PPI networks still have many false positive interactions and false negative edge loss due to the limitations of high-throughput experiments. In particular, the false negative errors restrict the search space of such conventional protein complex identification approaches. Thus, it has become one of the most challenging tasks in systems biology to automatically identify protein complexes.

Results

In this study, we propose a new algorithm, NEOComplex (NECC- and Ortholog-based Complex identification by multiple network alignment), which integrates functional orthology information that can be obtained from different types of multiple network alignment (MNA) approaches to expand the search space of protein complex detection. As part of our approach, we also define a new edge clustering coefficient (NECC) to assign weights to interaction edges in PPI networks so that protein complexes can be identified more accurately. The NECC is based on the intuition that there is functional information captured in the common neighbors of the common neighbors as well. Our results show that our algorithm outperforms well-known protein complex identification tools in a balance between precision and recall on three eukaryotic species: human, yeast, and fly. As a result of MNAs of the species, the proposed approach can tolerate edge loss in PPI networks and even discover sparse protein complexes which have traditionally been a challenge to predict.

Availability and Implementation

http://acolab.ie.nthu.edu.tw/bionetwork/NEOComplex

Supplementary information

Supplementary data are available at Bioinformatics online.
ISPRED4: interaction sites PREDiction in protein structures with a refining grammar model
Authors: Savojardo Castrense , Fariselli Piero , Martelli Pier Luigi , Casadio Rita
Published: January 2017

Motivation

The identification of protein–protein interaction (PPI) sites is an important step towards the characterization of protein functional integration in the cell complexity. Experimental methods are costly and time-consuming and computational tools for predicting PPI sites can fill the gaps of PPI present knowledge.

Results

We present ISPRED4, an improved structure-based predictor of PPI sites on unbound monomer surfaces. ISPRED4 relies on machine-learning methods and it incorporates features extracted from protein sequence and structure. Cross-validation experiments are carried out on a new dataset that includes 151 high-resolution protein complexes and indicate that ISPRED4 achieves a per-residue Matthew Correlation Coefficient of 0.48 and an overall accuracy of 0.85. Benchmarking results show that ISPRED4 is one of the top-performing PPI site predictors developed so far.

Availability and Implementation

ISPRED4 and datasets used in this study are available at http://ispred4.biocomp.unibo.it.
Computing Osmotic Permeabilities of Aquaporins AQP4, AQP5, and GlpF from Near-Equilibrium Simulations
Authors: Wambo Thierry Oscar , Rodriguez Roberto Alexis , Chen Liao Y
Published: January 2017

Measuring or computing the single-channel permeability of aquaporins/aquaglyceroporins (AQPs) has long been a challenge. The measured values scatter over an order of magnitude but the corresponding Arrhenius activation energies converge in the current literature. Osmotic flux through an AQP was simulated as water current forced through the channel by kilobar hydraulic pressure or theoretically approximated as single-file diffusion. In this paper, we report large scale simulations of osmotic current under sub M gradient through three water channels (the water-specific AQP4 and AQP5 along with aquaglyceroporin GlpF) using the mature particle mesh Ewald technique (PME) for which the established force fields have been optimized with known accuracy. These simulations were implemented with hybrid periodic boundary conditions devised to avoid the artifactitious mixing across the membrane in a regular PME simulation. The computed single-channel permeabilities are in agreement with recently refined experiments on GlpF. The Arrhenius activation energies extracted from our simulations for all the three AQPs agree with the in vitro measurements. The single-file diffusion approximations from our large-scale simulations are consistent with the current literature on smaller systems. From these unambiguous agreements among the in vitro and in silico studies, we observe the quantitative accuracy of the all-atom force fields of the current literature for water-channel biology. We also observe that AQP4, that is particularly rich in the central nervous system, is more efficient in water conduction and more temperature-sensitive than other water-specific channel proteins.
Efficacy of the β-lactam\β-lactamase inhibitor combination is linked to WhiB4 mediated changes in redox physiology ofMycobacterium tuberculosis
Authors: Mishra Saurabh , Shukla Prashant , Bhaskar Ashima , Anand Kushi , Baloni Priyanka , Jha Rajeev Kumar , Mohan Abhilash , Rajmani Raju S. , Nagaraja V. , Chandra Nagasuma , Singh Amit
Published: January 2017

Aims

Inhibition of β-lactamase by clavulanate (Clav) sensitizes multi-and extensively drug-resistantMycobacterium tuberculosis(Mtb) strains towards β-lactams such as amoxicillin (Amox). However, the underlying mechanism of howMtbresponds to Amox-Clav combination (Augmentin; AG) is not characterized.

Results

We integrated global expression profiling with the protein-protein interaction landscape and generated a genome-scale network ofMtbin response to AG. In addition to specific targets (e.g.,peptidoglycan biosynthesis and β-lactamase), the response to AG was also centered on redox-balance, central carbon metabolism (CCM), and respiration inMtb.We discovered that AG modulates superoxide levels, NADH/NAD+balance and mycothiol redox potential (EMSH) ofMtb. Higher intra-mycobacterialEMSHpotentiates mycobactericidal efficacy of AG, whereas lowerEMSHinduces tolerance. Further,Mtbresponds to AG via a redox-sensitive transcription factor, WhiB4.MtbΔwhiB4displayed higher expression of genes involved in β-lactam resistance along with those mediating respiration, CCM and redox balance. Moreimportantly, WhiB4 binds to the promoter regions and represses transcription of genes involved in β-lactamase expression in a redox-dependent manner. Lastly, whileMtbΔwhiB4maintained internalEMSH, exhibited greater β-lactamase activity and displayed AG-tolerance, overexpression of WhiB4 induced oxidative shift inEMSHand repressed β-lactamase activity to aggravate AG-mediated killing of drug-sensitive and –resistant strains ofMtb.

Innovation and Conclusions

This work demonstrate that efficacy of β-lactam\β-lactamase inhibitor combination can be attenuated by elevating mycobacterial antioxidant capabilities and potentiated by impairing redox buffering capacity ofMtb. The functional linkage between β-lactams, redox balance, and WhiB4 can be exploited to potentiate AG action against drug-resistantMtb.
Accessible, curated metagenomic data through ExperimentHub
Authors: Pasolli Edoardo , Schiffer Lucas , Manghi Paolo , Renson Audrey , Obenchain Valerie , Truong Duy Tin , Beghini Francesco , Malik Faizan , Ramos Marcel , Dowd Jennifer B. , Huttenhower Curtis , Morgan Martin , Segata Nicola , Waldron Levi
Published: January 2017

We present curatedMetagenomicData, a Bioconductor and command-line interface to thousands of metagenomic profiles from the Human Microbiome Project and other publicly available datasets, and ExperimentHub, a platform for convenient cloud-based distribution of data to the R desktop. The resource provides standardized per-participant metadata linked to bacterial, fungal, archaeal, and viral taxonomic abundances, as well as quantitative metabolic functional profiles. The datasets can be immediately analyzed in R or other software with a minimum of bioinformatic expertise and no preprocessing of data. We demonstrate identification of taxonomic/functional correlations, an investigation of gut “enterotypes”, and a comparison of the accuracy of disease classification from different data types. These documented analyses can be reproduced efficiently on a laptop, without the barriers of working with large-scale, raw sequencing data. The building and expansion of curatedMetagenomicData is based entirely on open source software and pipelines, to facilitate the addition of new microbiome datasets and methods.
A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression
Authors: Palhano-Fontes Fernanda , Barreto Dayanna , Onias Heloisa , Andrade Katia C , Novaes Morgana , Pessoa Jessica A , Mota-Rolim Sergio A , Osório Flavia , Sanches Rafael , dos Santos Rafael G , Tófoli Luís F , Oliveira Silveira Gabriela de , Yonamine Mauricio , Riba Jordi , Santos Francisco RR , Silva-Junior Antonio A , Alchieri João , Galvão-Coelho Nicole L , Lobão-Soares Bruno , Hallak Jaime , Arcoverde Emerson , Maia-de-Oliveira João P , Araújo Draulio B
Published: January 2017

Recent open label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. In order to further test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. Changes in depression severity were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at one (D1), two (D2) and seven (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all timepoints. MADRS scores were significantly lower in the ayahuasca group compared to placebo (at D1 and D2: p=0.04; and at D7: p<0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’ s d=0.84; D2: Cohen’ s d=0.84; D7: Cohen’ s d=1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% vs. 27%; p=0.04), while remission rate was marginally significant at D7 (36% vs. 7%, p=0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.
Fine-scale landscape genomics helps explain the slow spread ofWolbachiathrough theAedes aegyptipopulation in Cairns, Australia
Authors: Schmidt Thomas. L. , Filipović Igor. , Hoffmann Ary A. , Rašić Gordana
Published: January 2017

The endosymbiotic bacteriumWolbachiasuppresses the capacity for arboviral transmission in the mosquitoAedes aegypti, and can spread through wild mosquito populations following local introductions. Recent introductions in Cairns, Australia have demonstrated slower than expected spread, that could be due to: i) barriers toAe. aegyptidispersal; ii) leptokurtically distributed dispersal distances; and iii) intergenerational loss ofWolbachia. We investigated these three potential causes using genome-wide single-nucleotide polymorphisms (SNPs) and an assay for theWolbachiainfectionwMel in 161Ae. aegypticollected from Cairns in 2015. We observed a significant barrier effect of Cairns highways onAe. aegyptidispersal using distance-based redundancy analysis and patch-based simulation analysis. We detected putative full-siblings in ovitraps 1312m apart, suggesting long-distance female movement likely mediated by human transport. Finally, we found a pair of full-siblings of different infection status, suggesting loss ofWolbachiain the field. While the long-distance movement andWolbachialoss currently represent single observations, these findings together with the identified dispersal barriers can contribute to the slow spread ofWolbachiathrough theAe. aegyptipopulation in Cairns. Our landscape genomics approach can be extended to other host/symbiont systems that are being considered for biocontrol.
Experimental support that natural selection has shaped the latitudinal distribution of mitochondrial haplotypes in AustralianDrosophila melanogaster
Authors: Camus M. Florencia , Wolff Jonci N. , Sgrò Carla M. , Dowling Damian K.
Published: January 2017

Cellular metabolism is regulated by enzyme complexes within the mitochondrion, the function of which are sensitive to the prevailing temperature. Such thermal sensitivity, coupled with the observation that population frequencies of mitochondrial haplotypes tend to associate with latitude, altitude or climatic regions across species distributions, led to the hypothesis that thermal selection has played a role in shaping standing variation in the mitochondrial DNA (mtDNA) sequence. This hypothesis, however, remains controversial, and requires evidence that the distribution of haplotypes observed in nature corresponds with the capacity of these haplotypes to confer differences in thermal tolerance. Specifically, haplotypes predominating in tropical climates are predicted to encode increased tolerance to heat stress, but decreased tolerance to cold stress. We present direct evidence for these predictions, using mtDNA haplotypes sampled from the Australian distribution ofDrosophila melanogaster. We show that the ability of flies to tolerate extreme thermal challenges is affected by sequence variation across mtDNA haplotypes, and that the thermal performance associated with each haplotype corresponds with its latitudinal prevalence. The haplotype that predominates at low (subtropical) latitudes confers greater resilience to heat stress, but lower resilience to cold stress, than haplotypes predominating at higher (temperate) latitudes. We explore molecular mechanisms that might underlie these responses, presenting evidence that the effects are in part regulated by SNPs that do not change the protein sequence. Our findings suggest that standing variation in the mitochondrial genome can be shaped by thermal selection, and could therefore contribute to evolutionary adaptation under climatic stress.
Higher genetic risk of schizophrenia is associated with lower cognitive performance in healthy individuals
Authors: Shafee Rebecca , Nanda Pranav , Padmanabhan Jaya L. , Tandon Neeraj , Alliey-Rodriguez Ney , Keefe Richard S. E. , Hill Scot K. , Bishop Jeffrey R. , Clementz Brett A. , Tamminga Carol A. , Gershon Elliot S. , Pearlson Godfrey D. , Keshavan Matcheri S. , Sweeney John A. , Robinson Elise B. , McCarroll Steven A.
Published: January 2017

Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of the genetic risk of schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychosis patients; a measure of premorbid intelligence that is minimally affected by psychosis (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS and WRAT. Using genome-wide SNP data from 314 psychotic and 423 healthy research participants in the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Consortium, we investigated the association of PRSSCZwith BACS, WRAT and EY. Among apparently healthy individuals, greater genetic risk for schizophrenia (PRSSCZ) was associated with lower BACS scores (r = −0.19, p = 1 × 10−4at PT= 1 × 10−4) but did not associate with WRAT or EY, suggesting that these areas of cognition vary in their etiologic relationships with schizophrenia. Among individuals with psychosis, PRSSCZdid not associate with variation in cognitive performance. These findings suggest that the same cognitive abilities that are disrupted in psychotic disorders are also associated with schizophrenia genetic risk in the general population. Specific cognitive phenotypes, independent of education or general intelligence, could be more deeply studied for insight into the specific processes affected by the genetic influences on psychosis.

Significance

Psychotic disorders such as schizophrenia often involve profound cognitive deficits, the genetic underpinnings of which remain to be elucidated. Poor educational performance early in life is a well-known risk factor for future psychotic illness, potentially reflecting either shared genetic influences or other risk factors that are epidemiologically correlated. Here we show that, in apparently healthy individuals, common genetic risk factors for schizophrenia associate with lower performance in areas of cognition that are impaired in psychotic disorders but do not associate independently with educational attainment or more general measures of intelligence. These results suggest that specific cognitive phenotypes – independent of education or general intelligence – could be more deeply studied for insight into the processes affected by the genetic influences on psychosis.
Revealing the causative variant in Mendelian patient genomes without revealing patient genomes
Authors: Jagadeesh Karthik A. , Wu David J. , Birgmeier Johannes A. , Boneh Dan , Bejerano Gill
Published: January 2017

Given the rapidly growing utility of critical health information revealed in the human genome, secure genomic computation is essential to moving forward, especially as genome sequencing becomes commonplace. We devise and implement proof-of-principle computational operations for precisely identifying causal variants in Mendelian patients using secure multiparty computation methods based on Yao’s protocol. We show multiple real scenarios (small patient cohorts, trio analysis, two hospital collaboration) where the causal variant is discovered jointly, while keeping up to 99.7% of all participants’ most sensitive genomic information private. All similar operations performed today to diagnose such cases are done openly, keeping 0% of participants’ genomic information private. Our work will help usher in an era where genomes can be both utilized and truly protected.
Reverse-complement parameter sharing improves deep learning models for genomics
Authors: Shrikumar Avanti , Greenside Peyton , Kundaje Anshul
Published: January 2017

Deep learning approaches that have produced breakthrough predictive models in computer vision, speech recognition and machine translation are now being successfully applied to problems in regulatory genomics. However, deep learning architectures used thus far in genomics are often directly ported from computer vision and natural language processing applications with few, if any, domain-specific modifications. In double-stranded DNA, the same pattern may appear identically on one strand and its reverse complement due to complementary base pairing. Here, we show that conventional deep learning models that do not explicitly model this property can produce substantially different predictions on forward and reverse-complement versions of the same DNA sequence. We present four new convolutional neural network layers that leverage the reverse-complement property of genomic DNA sequence by sharing parameters between forward and reverse-complement representations in the model. These layers guarantee that forward and reverse-complement sequences produce identical predictions within numerical precision. Using experiments on simulated and in vivo transcription factor binding data, we show that our proposed architectures lead to improved performance, faster learning and cleaner internal representations compared to conventional architectures trained on the same data.
Colour Preferences of UK Garden Birds at Supplementary Seed Feeders
Authors: Rothery Luke , Scott Graham W. , Morrell Lesley J.
Published: January 2017

Supplementary feeding of garden birds has benefits for both bird populations and human wellbeing. Birds have excellent colour vision, and show preferences for food items of particular colours, but research into colour preferences associated with artificial feeders is limited to hummingbirds. Here, we investigated the colour preferences of common UK garden birds foraging at seed-dispensing artificial feeders containing identical food. We presented birds simultaneously with an array of eight differently coloured feeders, and recorded the number of visits made to each colour over 370 30-minute observation periods in the winter of 2014/15. In addition, we surveyed visitors to a garden centre and science festival to determine the colour preferences of likely purchasers of seed feeders. Our results suggest that silver and green feeders were visited by higher numbers of individuals of several common garden bird species, while red and yellow feeders received fewer visits. In contrast, people preferred red, yellow, blue and green feeders.
Ribosome reinitiation can explain length-dependent translation of messenger RNA
Authors: Rogers David W. , Böettcher Marvin A. , Traulsen Arne , Greig Duncan
Published: January 2017

Models of mRNA translation usually presume that transcripts are linear; upon reaching the end of a transcript each terminating ribosome returns to the cytoplasmic pool before initiating anew on a different transcript. A consequence of linear models is that faster translation of a given mRNA is unlikely to generate more of the encoded protein, particularly at low ribosome availability. Recent evidence indicates that eukaryotic mRNAs are circularized, potentially allowing terminating ribosomes to preferentially reinitiate on the same transcript. Here we model the effect of ribosome reinitiation on translation and show that, at high levels of reinitiation, protein synthesis rates are dominated by the time required to translate a given transcript. Our model provides a simple mechanistic explanation for many previously enigmatic features of eukaryotic translation, including the negative correlation of both ribosome densities and protein abundance on transcript length, the importance of codon usage in determining protein synthesis rates, and the negative correlation between transcript length and both codon adaptation and 5' mRNA folding energies. In contrast to linear models where translation is largely limited by initiation rates, our model reveals that all three stages of translation - initiation, elongation, and termination/reinitiation - determine protein synthesis rates even at low ribosome availability.
Eutrofication impacted temperate forest vegetation recently
Authors: Riofrio-Dillon Gabriela , Gegout Jean-Claude , Bertrand Romain
Published: January 2017

1. Nitrogen (N) is a key nutrient elements for ecosystems which has been highly impacted by human development and activities since the early 20th century. Despite that changes in N-availability have been demonstrated to impact forests, we still miss evidence of its effect on species composition over the long-term.
2. Based on a large number of floristic observations (n = 45 604), the French forest status related to soil N-availability was reconstructed from herb species assemblage between 1910 and 2010 using both a bioindication approach and a spatiotemporal sampling aiming to pair past and recent floristic observations.
3. We showed that soil N content bioindicated from forest herb communities was higher at the start of the 20th century than over the 2005-2010 period. It decreased more or less continuously until 1975 and 2005 in coniferous (mean ΔC:N=+0.79) and broadleaved (mean ΔC:N=+0.74) forests, respectively, and then was lower than the most recent bioindicated N level observed over the 2005-2010 period (mean ΔC:N=-0.10 and -0.16, respectively). Spatial analysis confirmed the temporal trends with a decrease and increase in forest surface areas where soil N impoverishment and enrichment have been bioindicated over the time, respectively.
4. N bioindicated trends are opposite to changes in N atmospheric deposition compared the 2005-2010 period, while they follow temporal variation in mean N deposition until 1990.
Synthesis. Our results showed that forest herb communities have been reshuffled in regards of their soil N requirements over the 20th century highlighting that temporal changes in soil N supply have impacted the understory species composition of forest. We evidenced changes in communities towards less nitrophilous plant assemblage followed by a recent eutrophication since 2005. We propose that the nitrogen forest vegetation status is likely related to N atmospheric deposition trend, but also to both acidification, climate change and forestry management which impacted organic matter decomposition and soil N mineralization through effects on soil microbial and fauna activities. The current eutrophication observed in forest herb communities is worrisome for temperate forest ecosystem and its functioning in regards of biodiversity homogenization which often accompanied such a community reshuffling.
High GC Content Causes Orphan Proteins to be Intrinsically Disordered
Authors: Basile Walter , Sachenkova Oxana , Light Sara , Elofsson Arne
Published: January 2017

De novocreation of protein coding genes involves the formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the populationThese orphan proteins need to, at the bare minimum, not cause serious harm to the organism, meaning that they should for instance not aggregate. Therefore, although the creation of short ORFs could be truly random, the fixation should be subjected to some selective pressure. The selective forces acting on orphan proteins have been elusive, and contradictory results have been reported. InDrosophilayoung proteins are more disordered than ancient ones, while the opposite trend is present in yeast. To the best of our knowledge no valid explanation for this difference has been proposed.

To solve this riddle we studied structural properties and age of proteins in 187 eukaryotic organisms. We find that, with the exception of length, there are only small differences in the properties between proteins of different ages. However, when we take the GC content into account we noted that it could explain the opposite trends observed for orphans in yeast (low GC) andDrosophila(high GC). GC content is correlated with codons coding for disorder promoting amino acids. This leads us to propose that intrinsic disorder is not a strong determining factor for fixation of orphan proteins. Instead these proteins largely resemble random proteins given a particular GC level. During evolution the properties of a protein change faster than the GC level causing the relationship between disorder and GC to gradually weaken.

Author Summary

We show that the GC content of a genome is of great importance for the properties of an orphan protein. GC content affects the frequency of the codons and this affects the probability for each amino acid to be included in ade novocreated protein. The codons encoding for Ala, Pro and Gly contain 80% GC, while codons for Lys, Phe, Asn, Tyr and Ile contain 20% or less. The three high GC amino acids are all disorder promoting, while Phe, Tyr and Ile are order promoting. Therefore, random protein sequences at a high GC will be more disordered than the ones created at a low GC. The structural properties of the youngest proteins match to a large degree the properties of random proteins when the GC content is taken into account. In contrast, structural properties of ancient proteins only show a weak correlation with GC content. This suggests that even after fixation in the population, proteins largely resemble random proteins given a certain GC content. Thereafter, during evolution the correlation between structural properties and GC weakens.
European Flint reference sequences complement the maize pan-genome
Authors: Unterseer Sandra , Seidel Michael A. , Bauer Eva , Haberer Georg , Hochholdinger Frank , Opitz Nina , Marcon Caroline , Baruch Kobi , Spannagl Manuel , Mayer Klaus F.X. , Schön Chris-Carolin
Published: January 2017

The genomic diversity of maize is reflected by a large number of SNPs and substantial structural variation. Here, we report thede novoassembly of two European Flint maize lines to remedy the scarcity of sequence resources for the Flint pool. EP1 and F7 are important founder lines of European hybrid breeding programs. The lines were sequenced on an Illumina platform at 320X and 225X coverage. Using NRGene´s DeNovoMAGIC 2.0 technology, pseudochromosomes were assembled encompassing a total of 2,463 Mb for EP1 and 2,405 Mb for F7. Structural and functional annotation of the two genomes is currently in progress. The two high-qualityde novoassemblies complement the existing maize pan-genome and will pave the way for future functional and comparative studies.
Colour vision models: a practical guide, some simulations, andcolourvisionR package
Authors: Gawryszewski Felipe M.
Published: January 2017

Human colour vision differs from the vision of other animals. The most obvious differences are the number and type of photoreceptors in the retina. E.g., while humans are insensitive to ultraviolet (UV) light, most non-mammal vertebrates and insects have a colour vision that spans into the UV. The development of colour vision models allowed appraisals of colour vision independent of the human experience. These models are now widespread in ecology and evolution fields. Here I present a guide to colour vision modelling, run a series of simulations, and provide a R package –colourvision– to facilitate the use of colour vision models.

I present the mathematical steps for calculation of the most commonly used colour vision models: Chittka (1992) colour hexagon, Endler & Mielke (2005) model, and Vorobyev & Osorio (1998) linear and log-linear receptor noise limited models (RNL). These models are then tested using identical simulated and real data. These comprise of reflectance spectra generated by a logistic function against an achromatic background, achromatic reflectance against an achromatic background, achromatic reflectance against a chromatic background, and real flower reflectance data against a natural background reflectance.

When the specific requirements of each model are met, between model results are, overall, qualitatively and quantitatively similar. However, under many common scenarios of colour measurements, models may generate spurious values and/or considerably different predictions. Models that log-transform data and use relative photoreceptor outputs are prone to generate unrealistic results when the stimulus photon catch is smaller than the background photon catch. Moreover, models may generate unrealistic results when the background is chromatic (e.g. leaf reflectance) and the stimulus is an achromatic low reflectance spectrum.

Colour vision models are a valuable tool in several ecology and evolution subfields. Nonetheless, knowledge of model assumptions, careful analysis of model outputs, and basic knowledge of calculation behind each model are crucial for appropriate model application, and generation of meaningful and reproducible results. Other aspects of vision not incorporated into these models should be considered when drawing conclusion from model results.
The Negev hospital-university-based (HUB) autism database
Authors: Meiri Gal , Dinstein Ilan , Michaelowski Analya , Flusser Hagit , Ilan Michal , Faroy Michal , Bar-Sinai Asif , Manelis Liora , Stolowicz Dana , Yosef Lili Lea , Davidovitch Nadav , Golan Hava , Arbelle Shosh , Menashe Idan
Published: January 2017

Elucidating the heterogeneous etiologies of autism will require investment in comprehensive longitudinal data acquisition from large community based cohorts. With this in mind, we have established a hospital-university-based (HUB) database of autism which incorporates prospective and retrospective data from a large and ethnically diverse population. Here we present initial findings from 188 children who were diagnosed with autism during the first eighteen months of the study. The unique characteristics of this cohort included: significant differences between Bedouin and Jewish children in different risk factors and clinical characteristics; complete birth records for >90% of the children; and a high frequency of consanguineous marriages. Thus, the Negev HUB autism database comprises a remarkably unique resource to study different aspects of autism.
No evidence of early head circumference enlargements in children later diagnosed with autism in Israel
Authors: Dinstein Ilan , Haar Shlomi , Atsmon Shir , Schtaerman Hen
Published: January 2017

Background

Large controversy exists regarding the potential existence and clinical significance of larger brain volumes in toddlers who later develop autism. Assessing this relationship is important for determining the clinical utility of early head circumference (HC) measures and for assessing the validity of the early overgrowth hypothesis of autism, which suggests that early accelerated brain development may be a hallmark of the disorder

Method

We performed a retrospective comparison of HC, height, and weight measurements between 66 toddlers who were later diagnosed with autism and 66 matched controls. These toddlers represent an unbiased regional sample from a single health service provider in the southern district of Israel. Using 4-12 measurements between birth and the age of two, we were able to characterize individual HC, height, and weight development with high precision and fit a negative exponential growth model to the data of each toddler with exceptional accuracy

Results

The analyses revealed that HC sizes and growth rates were not significantly larger in toddlers with autism even when stratifying the autism group based on verbal capabilities at the time of diagnosis. In addition, there were no significant correlations between ADOS scores at the time of diagnosis and HC at any time-point during the first two years of life

Conclusions

These negative results add to accumulating evidence, which suggest that brain volume is not necessarily larger in toddlers who develop autism. While early brain overgrowth may characterize specific individuals with autism, it is not likely to represent a common etiology of the entire autism population