bluuebunny/crossref_metadata_2025 huggingface dataset:
Acuticoccus sediminis sp. nov., isolated from deep-sea sediment of the Indian Ocean and proposal of Acuticoccaceae fam. nov
Authors: Lai Qiliang , Liu Xiupian , Sun Fenqing , Shao Zongze
Published: February 2019

A Gram-staining negative, aerobic, oval-shaped bacterium, designated strain PTG4-2T, was isolated from deep-sea sediment of the Indian Ocean. Growth was observed with 1–9 % (w/v) NaCl with optimal growth with 3 %, at pH 6.0–10.0 with an optimum of pH 7.0, and at 4–40 °C with an optimum of 30 °C. Positive for catalase and oxidase. The results of a 16S rRNA gene sequence comparison indicated that PTG4-2T was most closely related to Acuticoccus yangtzensis JL1095T (97.3 %), followed by Acuticoccus kandeliae J103T (96.5 %), all other species shared <93 % sequence similarity. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that PTG4-2T forms a distinct lineage within the genus

Acuticoccus

, and revealed that the genus

Acuticoccus

forms a novel family-level clade in the order

Rhizobiales

. The ANI and the DNA–DNA hybridization estimate values between PTG4-2T and two type strains (A. yangtzensis JL1095T and A. kandeliae J103T) were 79.9–76.2 % and 23.1–20.8 %, respectively. PTG4-2T contained Q-10 as the predominant ubiquinone. The principal fatty acids (>5 %) were summed feature 8 [C18 : 1
ω7c/ω6c (72.2 %)], C18 : 0 (8.4 %), C20 : 1
ω7c (6.4 %) and C16 : 0 (6.3 %). The polar lipids consisted of phosphatidylglycerol, three unidentified phospholipids, two unidentified glycolipids, one unidentified aminolipid and one unknown lipid. The DNA G+C content of PTG4-2T is 69.2 mol%. On the basis of the polyphasic taxonomic evidence presented in this study, PTG4-2T should be classified as representing a novel species of the genus

Acuticoccus

, for which the name

Acuticoccus
sediminis sp. nov. is proposed, with the type strain PTG4-2T (=MCCC 1A01274T=KCTC 52323T). In addition, a novel family, Acuticoccaceae fam. nov., is proposed to accommodate the genus

Acuticoccus

.
Wave 2 strains of atypical Vibrio cholerae El Tor caused the 2009–2011 cholera outbreak in Papua New Guinea
Authors: Greenhill Andrew R. , Mutreja Ankur , Bulach Dieter , Belousoff Matthew J. , Jonduo Marinjho H. , Collins Deirdre A. , Kas Monalisa P. , Wapling Johanna , Seemann Torsten , Lafana Alice , Dougan Gordon , Brown Mark V. , Horwood Paul F.
Published: February 2019

Vibrio cholerae

is the causative agent of cholera, a globally important human disease for at least 200 years. In 2009–2011, the first recorded cholera outbreak in Papua New Guinea (PNG) occurred. We conducted genetic and phenotypic characterization of 21 isolates of

V. cholerae
, with whole-genome sequencing conducted on 2 representative isolates. The PNG outbreak was caused by an atypical El Tor strain harbouring a tandem repeat of the CTX prophage on chromosome II. Whole-genome sequence data, prophage structural analysis and the absence of the SXT integrative conjugative element was indicative that the PNG isolates were most closely related to strains previously isolated in South-East and East Asia with affiliations to global wave 2 strains. This finding suggests that the cholera outbreak in PNG was caused by an exotic (non-endemic) strain of

V. cholerae

that originated in South-East Asia.
More Reliable EEG Electrode Digitizing Methods Can Reduce Source Estimation Uncertainty, But Current Methods Already Accurately Identify Brodmann Areas
Authors: Shirazi Seyed Yahya , Huang Helen J.
Published: February 2019

Electroencephalography (EEG) and source estimation can be used to identify brain areas activated during a task, which could offer greater insight on cortical dynamics. Source estimation requires knowledge of the locations of the EEG electrodes. This could be provided with a template or obtained by digitizing the EEG electrode locations. Operator skill and inherent uncertainties of a digitizing system likely produce a range of digitization reliabilities, which could affect source estimation and the interpretation of the estimated source locations. Here, we compared the reliability of five digitizing methods (ultrasound, structured-light 3D scan, infrared 3D scan, motion capture probe, and motion capture) and determined the relationship between digitization reliability and source estimation uncertainty, assuming other contributors to source estimation uncertainty were constant. We digitized a mannequin head using each method five times and quantified the reliability and validity of each method. We created five hundred sets of electrode locations based on our reliability results and applied a dipole fitting algorithm (DIPFIT) to perform source estimation. The motion capture method, which recorded the locations of markers placed directly on the electrodes had the best reliability with an average electrode variability of 0.001cm. Then, in order of decreasing reliability were the method using a digitizing probe in the motion capture system, an infrared 3D scanner, a structured-light 3D scanner, and an ultrasound digitization system. Unsurprisingly, uncertainty of the estimated source locations increased with greater variability of EEG electrode locations and less reliable digitizing systems. If EEG electrode location variability was ~ 1 cm, a single source could shift by as much as 2 cm. To help translate these distances into practical terms, we quantified Brodmann area accuracy for each digitizing method and found that the average Brodmann area accuracy for all digitizing methods was > 80%. Using a template of electrode locations reduced the Brodmann area accuracy to ~ 50%. Overall, more reliable digitizing methods can reduce source estimation uncertainty, but the significance of the source estimation uncertainty depends on the desired spatial resolution. For accurate Brodmann area identification, any of the digitizing methods tested can be used confidently.
A Comprehensive Assessment of Demographic, Environmental and Host Genetic Associations with Gut Microbiome Diversity in Healthy Individuals
Authors: Scepanovic Petar , Hodel Flavia , Mondot Stanislas , Partula Valentin , Byrd Allyson , Hammer Christian , Alanio Cécile , Bergstedt Jacob , Patin Etienne , Touvier Mathilde , Lantz Olivier , Albert Matthew L. , Duffy Darragh , Quintana-Murci Lluis , Fellay Jacques ,   The Milieu Intérieur Consortium
Published: February 2019

Background

The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1,000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20 – 69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition.

Results

Among 110 demographic, clinical and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between >5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics.

Conclusion

In a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals.
Defining region-specific masks for reliable depth-dependent analysis of fMRI data
Authors: Weldon Kimberly B. , Burton Philip C. , Grant Andrea N. , Yacoub Essa , Olman Cheryl A.
Published: February 2019

In high-field fMRI research, anatomical reference information (e.g., gray matter (GM) segmentation, cortical depth delineation) is often defined in volumes acquired with pulse sequences subject to different distortions than those in functional volumes. In these cases, reliable interpretation of ultra-high resolution fMRI data depends on excellent cross-modal registration of functional volumes to reference anatomical volumes. In this paper, we describe a two-step approach to automating assessments of cross-modal registration quality for the purpose of guiding depth-dependent analysis. First, each functional/anatomical registration was scored by the ratio of the number of GM voxels in the functional data overlapping anatomical GM to the number of GM voxels in the functional data overlapping anatomical white matter (WM). This GM:WM overlap ratio provided an objective metric for determining whether an alignment algorithm had converged on a solution that would pass visual inspection. Second, surface-based maps indicating the consistency of overlap between functional and anatomical GM throughout the GM depth were generated for the entire region of cortex covered by the experiment. These maps served as a mask for the purpose of excluding regions where registration between functional and anatomical data was inadequate and thus unable to support depth-dependent analyses. We found, for both real and simulated data, that functional response profiles that were less biased toward superficial responses in regions where these metrics indicated satisfactory registration.
Use of CRISPR/Cas9 Gene Targeting to Conditionally Delete Glucocorticoid Receptors in Rat Brain
Authors: Scheimann Jessie R. , Moloney Rachel D. , Mahbod Parinaz , Morano Rachel L. , Fitzgerald Maureen , Hoskins Olivia , Packard Benjamin A. , Hu Yueh-Chiang , Herman James P.
Published: February 2019

Glucocorticoid receptors (GR) have diverse functions relevant to maintenance of homeostasis and adaptation to environmental challenges. Understanding the importance of tissue-specific GR function in physiology and behavior has been hampered by near-ubiquitous localization in brain and body. Here we use CRISPR/Cas9 gene editing to create a conditional GR knockout in Sprague Dawley rats. To test the impact of cell-and region-specific GR deletion on physiology and behavior, we targeted GR knockout to output neurons of the prelimbic cortex.

Prelimbic deletion of GR in females caused deficits in acquisition and extinction of fear memory during auditory fear conditioning, whereas males exhibit enhanced active-coping behavior during forced swim. Our data support the utility of this conditional knockout rat to afford high-precision deletion of GR across a variety of contexts, ranging from neuronal depletion to circuit-wide manipulations, leveraging the behavioral tractability and enhanced brain size of the rat as a model organism.
DeepSV: Accurate calling of genomic deletions from high-throughput sequencing data using deep convolutional neural network
Authors: Cai Lei , Wu Yufeng , Gao Jingyang
Published: February 2019

Background

Calling genetic variations from sequence reads is an important problem in genomics. There are many existing methods for calling various types of variations. Recently, Google developed a method for calling single nucleotide polymorphisms (SNPs) based on deep learning. Their method visualizes sequence reads in the forms of images. These images are then used to train a deep neural network model, which is used to call SNPs. This raises a research question: can deep learning be used to call more complex genetic variations such as structural variations (SVs) from sequence data?

Results

In this paper, we extend this high-level approach to the problem of calling structural variations. We present DeepSV, an approach based on deep learning for calling long deletions from sequence reads. DeepSV is based on a novel method of visualizing sequence reads. The visualization is designed to capture multiple sources of information in the sequence data that are relevant to long deletions. DeepSV also implements techniques for working with noisy training data. DeepSV trains a model from the visualized sequence reads and calls deletions based on this model. We demonstrate that DeepSV outperforms existing methods in terms of accuracy and efficiency of deletion calling on the data from the 1000 Genomes Project.

Conclutions

Our work shows that deep learning can potentially lead to effective calling of different types of genetic variations that are complex than SNPs.

Availability and implementation

DeepSV’s source code and sample result as part of this project are readily available from GitHub at https://github.com/CSuperlei/DeepSV/.
Diurnal variations in serum metabolites of wintering redheaded buntings
Authors: Gupta Neelu Jain , Das Samya , Das Mrinal , Arya Rakesh , Nanda Ranjan Kumar
Published: February 2019

Daily behavioural and physiological changes in bird may reflect in biofluid metabolite composition. Locomotor activity, food intake and body temperature of group (n=7) of male migratory redheaded buntings held under short days (8L:16D, SD) were monitored besides blood sampling at midday (ZT4: 4 hours zeitgeber time starting ZT0 as lights ‘on’) and midnight (ZT16). The birds exhibited higher activity and increased feeding during daytime with negligible activity and feeding at night. Gas chromatography mass spectrometry and chemo-metric analyses of bird serum revealed higher levels of lipid (palmitic, oleic and linoleic acids) and protein (uric acid and proline) catabolites in daytime serum samples as compared to night samples. Higher night-time levels of short chain fatty acids indicated utilization of glucose and lipolysis in night fasted birds. High night-time levels of taurine, a sulphur amino acid has adaptive advantage to night migratory song birds. The diurnal differences in metabolite patterns suggests differential energy expenditure during day and renders survival benefit to buntings as night migrants. We propose a GCMS method that could be useful to unravel different annual life-history stages including migration.
An early Myc-dependent transcriptional program underlies enhanced macromolecular biosynthesis and cell growth during B-cell activation
Authors: Tesi Alessandra , Pretis Stefano de , Furlan Mattia , Filipuzzi Marco , Morelli Marco J. , Andronache Adrian , Doni Mirko , Verrecchia Alessandro , Pelizzola Mattia , Amati Bruno , Sabò Arianna
Published: February 2019

Upon activation, lymphocytes exit quiescence and undergo substantial increases in cell size, accompanied by activation of energy-producing and anabolic pathways, widespread chromatin decompaction and elevated transcriptional activity. These changes depend upon prior induction of the Myc transcription factor, but how Myc controls them remains unclear. We addressed this issue in primary mouse B-cells, based on conditional deletion of the c-myc gene, followed by LPS stimulation. Myc was rapidly induced, became detectable on virtually all active promoters and enhancers, but had no direct impact on global transcriptional activity. Instead, Myc contributed to the swift up- and down-regulation of several hundred genes, including many known regulators of the aforementioned cellular processes. Myc-activated promoters were enriched for E-box consensus motifs, bound Myc at the highest levels and showed enhanced RNA Polymerase II recruitment, the opposite being true at down-regulated loci. Remarkably, the Myc-dependent signature identified in activated B-cells was also enriched in Myc-driven B-cell lymphomas: hence, besides modulation of new cancer-specific programs, the oncogenic action of Myc may largely rely on sustained deregulation of its normal physiological targets.
Dual Acting Small-Molecule Inhibitors Targeting Mycobacterial DNA Replication
Authors: Singh Meenakshi , Ilic Stefan , Tam Benjamin , Ben-Ishay Yasmin , Sherf Dror , Pappo Doron , Akabayov Barak
Published: February 2019

Mycobacterium tuberculosis(Mtb) is a pathogenic bacterium and a causative agent of tuberculosis (TB), a disease that kills more than 1.5 million people worldwide annually. One of the main reasons for this high mortality rate is the evolution of newMtbstrains that are resistant to available antibiotics. Therefore, new therapeutics for TB are in constant demand. Here we report the development of such inhibitors that target two DNA replication enzymes ofMtb, namely DnaG primase and DNA gyrase, which share a conserved TOPRIM fold near the inhibitors’ binding site. The molecules were developed on the basis of previously reported inhibitors for T7 DNA primase that bind near the TOPRIM fold. In order to improve the physicochemical properties of the molecules as well as their inhibitory effect on primase and gyrase, 49 novel compounds were synthesized as potential drug candidates in three stages of optimization. The last stage of chemical optimization yielded two novel inhibitors for the fast-growing nonpathogenic modelMycobacterium smegmatis(Msmg).
Internal noise measures in coarse and fine motion direction discrimination tasks, and the correlation with autism traits
Authors: Orchard Edwina , Dakin Steven , van Boxtel Jeroen J.A.
Published: February 2019

Motion perception is essential for visual guidance of behaviour and is known to be limited by both internal additive noise (arising from random fluctuations in neural activity), and by motion pooling (global integration of local motion signals across space). People with autism spectrum disorder (ASD) display abnormalities in motion processing, which has been linked to both elevated noise and abnormal pooling. However, to date, the impact of a third limit - induced internal noise (internal noise that scales up with increases is external noise) - has not been investigated in motion perception of any group. Here, we describe a new double-pass motion direction discrimination paradigm that quantifies additive noise, induced noise, and motion pooling. We measure the impact of induced noise on direction discrimination, which we ascribe to fluctuations in decision-related variables. We report that internal noise is higher individuals with high ASD traits only on coarse but not fine motion direction discrimination tasks. However, we report no significant correlations between autism traits, and additive noise, induced noise or motion pooling, in either task. We conclude that internal noise may be higher in individuals with many ASD traits, and that the assessment of induced internal noise is a useful way of exploring decision-related limits on motion perception, irrespective of ASD traits.
Diversity of Escherichia coli from the enteric microbiota in patients with Escherichia coli bacteraemia
Authors: Mosavie Mia , Blandy Oliver , Jauneikaite Elita , Caldas Isabel , Ellington Matthew J. , Woodford Neil , Sriskandan Shiranee
Published: February 2019

Objective

The increase in Escherichia coli bloodstream infections mandates better characterisation of the relationship between commensal and invasive isolates. This study established a simple approach to characterize diversity of E. coli in the gut reservoir from patients with either E. coli bacteraemia, other Gram-negative bacteraemia, or patients without bacteraemia not receiving antibiotics. Stool or rectal swabs from patients in the three groups were cultured on selective chromogenic agar. Genetic diversity of E. coli in gut microbiota was estimated by RAPD-PCR.

Results

Enteric samples from E. coli bacteraemia patients yielded a median of one E. coli RAPD pattern (range 1-4) compared with two (range 1-5) from groups without E. coli bacteraemia. Of relevance to large-scale clinical studies, observed diversity of E. coli among E. coli bacteraemia patients was not significantly altered by sample type (rectal swab or stool), nor by increasing the colonies tested beyond ten. Overall, hospitalised patients demonstrated an apparently limited diversity of E. coli in the enteric microbiota and this was further reduced in those with E. coli bacteraemia. The reduced diversity of E. coli within the gut during E. coli bacteraemia raises the possibility that dominant strains may outcompete other lineages in patients with bloodstream infection.
Comparative Genomics of Six Juglans Species Reveals Patterns of Disease-associated Gene Family Contractions
Authors: Trouern-Trend Alex , Falk Taylor , Zaman Sumaira , Caballero Madison , Neale David B. , Langley Charles H. , Dandekar Abhaya , Stevens Kristian A. , Wegrzyn Jill L.
Published: February 2019

Juglans (walnuts), the most speciose genus in the walnut family (Juglandaceae) represents most of the family’s commercially valuable fruit and wood-producing trees and includes several species used as rootstock in agriculture for their resistance to various abiotic and biotic stressors. We present the full structural and functional genome annotations of six Juglans species and one outgroup within Juglandaceae (Juglans regia, J. cathayensis, J. hindsii, J. microcarpa, J. nigra, J. sigillata and Pterocarya stenoptera) produced using BRAKER2 semi-unsupervised gene prediction pipeline and additional in-house developed tools. For each annotation, gene predictors were trained using 19 tissue-specific J. regia transcriptomes aligned to the genomes. Additional functional evidence and filters were applied to multiexonic and monoexonic putative genes to yield between 27,000 and 44,000 high-confidence gene models per species. Comparison of gene models to the BUSCO embryophyta dataset suggested that, on average, genome annotation completeness was 89.6%. We utilized these high quality annotations to assess gene family evolution within Juglans and among Juglans and selected Eurosid species, which revealed significant contractions in several gene families in J. hindsii including disease resistance-related Wall-associated Kinase (WAK) and Catharanthus roseus Receptor-like Kinase (CrRLK1L) and others involved in abiotic stress response. Finally, we confirmed an ancient whole genome duplication that took place in a common ancestor of Juglandaceae using site substitution comparative analysis.

SIGNIFICANCE

High-quality full genome annotations for six species of walnut (Juglans) and a wingnut (Pterocarya) outgroup were constructed using semi-unsupervised gene prediction followed by gene model filtering and functional characterization. These annotations represent the most comprehensive set for any hardwood genus to date. Comparative analyses based on the gene models uncovered rapid evolution in multiple gene families related to disease-response and a whole genome duplication in a Juglandaceae common ancestor.
Recollection and prior knowledge recruit the left angular gyrus during recognition
Authors: Bellana B. , Ladyka-Wojcik N. , Lahan S. , Moscovitch M. , Grady C. L.
Published: February 2019

The human angular gyrus (AG) is implicated in recollection, or our ability to retrieve detailed memory content from a specific study episode. Parallel work also highlights a key role of the AG in the representation of general knowledge and semantics. How these two lines of research converge remains unclear. The present fMRI experiment used a remember-know paradigm with famous and non-famous faces to test whether activity in the AG could be modulated by both task-specific recollection and general prior knowledge in the same participants. Increased BOLD activity in the left AG was observed during both recollection in the absence of prior knowledge (i.e., recollected > non-recollected or correctly rejected non-famous faces) and when prior knowledge was accessed in the absence of recollection (i.e., famous > non-famous correct rejections). This pattern was unique to the left AG, and was not present in any other regions of the lateral inferior parietal lobe. Furthermore, the response profile of the left AG was consistent with accounts of recollection strength. Recollection-related activity was greater for faces with longer exposures at encoding than those with shorter exposures and was greater for stimuli with prior knowledge than those without, despite prior knowledge being incidental to the recognition decision. Therefore, the left AG is recruited during the access of both task-specific recollection and general prior knowledge, with greater activity as the amount of retrieved information increases, irrespective of its episodic or semantic nature.

Significance Statement

The human angular gyrus (AG) is often implicated in our ability to remember past events. A separate line of research examining our ability to represent general knowledge has also highlighted the AG as a core region of interest. To reconcile these separate views of AG function, we used fMRI to test whether the human left AG was sensitive to remembering details from a specific study episode (i.e., recollection) or more general prior knowledge, within the same participants. Overall, activity in the left AG was sensitive to both recollection and prior knowledge, suggesting any complete functional account of the left AG during retrieval must consider its sensitivity to both kinds of mnemonic representations.
Two resistance nodulation division-family efflux pumps inChromobacteriumspecies and their role in antibiotic resistance and tolerance
Authors: Benomar Saida , Evans Kara C , Unckless Robert L , Chandler Josephine R
Published: February 2019

Very little is known of the antibiotic resistance mechanisms of members of theChromobacteriumgenus. In previous studies ofChromobacterium subtsugae(formerlyC. violaceum) strain CV017, we identified a resistance nodulation division (RND)-family efflux pump (CdeAB-OprM). Here, we show thecdeAB-oprMgenes are widely distributed in members of theChromobacteriumgenus. We use antimicrobial susceptibility testing with a CV017cdeAB-oprMmutant to show the products of these genes confers resistance to a variety of antibiotics including ciprofloxacin, a clinically important antibiotic. We also identified a related RND-family pump,cseAB-oprN, in the genome of CV017 and otherC. subtsugaespecies, that is not present in other members of theChromobacteriumgenus. We demonstrate that CdeAB-OprM and CseAB-OprN are both transcriptionally induced in CV017 cells treated with sub-lethal antibiotic concentrations and they are important for induction of tolerance to different antibiotics. While CdeAB-OprM has a broad antibiotic specificity, the CseAB-OprN system is highly specific for a ribosome-targeting antibiotic produced by the saprophytic bacteriumBurkholderia thailandensis,bactobolin. Finally, we use a previously developedB. thailandensis-C. subtsugaeCV017 co-culture model to demonstrate that adding sub-lethal bactobolin at the beginning of co-culture growth increases the ability of CV017 to compete withB. thailandensisin a manner that is dependent on the CseAB-OprN system. Our results provide new information on the antibiotic resistance mechanisms ofChromobacteriumspecies and highlight the importance of efflux pumps during competition with other bacterial species.

IMPORTANCE

This study describes two closely related efflux pumps in members of theChromobacteriumgenus, which includes opportunistic but often-fatal pathogens and species with highly versatile metabolic capabilities. Efflux pumps remove antibiotics from the cell and are important for antibiotic resistance. One of these pumps is broadly distributed in theChromobacteriumgenus and increases resistance to clinically relevant antibiotics. The other efflux pump is present only inChromobacterium subtsugaeand is highly specific for bactobolin, an antibiotic produced by the soil saprophyteBurkholderia thailandensis. We demonstrate these pumps can be activated to increase resistance by their antibiotic substrates, and that this activation is important forC. subtsugaeto survive in a laboratory competition experiment withB. thailandensis.These results have implications for managing antibiotic-resistantChromobacteriuminfections, bioengineering ofChromobacteriumspecies, and for understanding the evolution of efflux pumps.
EpiAlignment: alignment with both DNA sequence and epigenomic data
Authors: Lu Jia , Cao Xiaoyi , Zhong Sheng
Published: February 2019

Comparative epigenomics, by subjecting both epigenome and genome to interspecies comparison, has become a powerful approach to reveal regulatory features of the genome. Thus elucidated regulatory features surpassed the information derived from comparison of genomic sequences alone. Here, we present EpiAlignment, a web-based tool to align genomic regions with both DNA sequence and epigenomic data. EpiAlignment takes DNA sequence and epigenomic profiles derived by ChIP-seq, DNase-seq, or ATAC-seq from two species as input data, and outputs the best semi-global alignments. These alignments are based on EpiAlignment scores, computed by a dynamic programming algorithm that accounts for both sequence alignment and epigenome similarity. For timely response, the EpiAlignment web server automatically initiates up to 140 computing threads depending on the size of user input data. For users’ convenience, we have pre-compiled the comparable human and mouse epigenome datasets in matched cell types and tissues from the Roadmap Epigenomics and ENCODE consortia. Users can either upload their own data or select pre-compiled datasets as inputs for EpiAlignment analyses. Results are presented in graphical and tabular formats where the entries can be interactively expanded to visualize additional features of these aligned regions. EpiAlignment is available at https://epialign.ucsd.edu/.
PathRacer: racing profile HMM paths on assembly graph
Authors: Shlemov Alexander , Korobeynikov Anton
Published: February 2019

Recently large databases containing profile Hidden Markov Models (pHMMs) emerged. These pHMMs may represent the sequences of antibiotic resistance genes, or allelic variations amongst highly conserved housekeeping genes used for strain typing, etc. The typical application of such a database includes the alignment of contigs to pHMM hoping that the sequence of gene of interest is located within the single contig. Such a condition is often violated for metagenomes preventing the effective use of such databases.

We present PathRacer — a novel standalone tool that aligns profile HMM directly to the assembly graph (performing the codon translation on fly for amino acid pHMMs). The tool provides the set of most probable paths traversed by a HMM through the whole assembly graph, regardless whether the sequence of interested is encoded on the single contig or scattered across the set of edges, therefore significantly improving the recovery of sequences of interest even from fragmented metagenome assemblies.

Availability

http://cab.spbu.ru/software/pathracer/
Proteins encoded by Novel ORFs have increased disorder but can be biochemically regulated and harbour pathogenic mutations
Authors: Jagannathan N. Suhas , Meena Narendra , Bhayankaram Kethaki Prathivadi , Prabakaran Sudhakaran
Published: February 2019

Recent evidence has suggested that protein or protein-like products can be encoded by previously uncharacterized Open Reading Frames (ORFs) that we define as Novel Open Reading Frames (nORFs)1,2. These nORFs are present in both coding and non coding regions of the human genome and the novel proteins that they encode have increased the number and complexity of cellular proteome from bacteria to humans. It is a conundrum whether these protein or protein-like products could play any significant functional biological role. But hopes have been raised to target them for anticancer and antimicrobial therapy3,4. To infer whether these novel proteins can perform biological functions, we used computational predictions to systematically investigate whether their amino acid sequences can form ordered or disordered structures. Our results indicated that that these novel proteins have significantly higher predicted disorder structure compared to all known proteins, yet we do not find any correlation between the pathogenicity of the mutations and whether they are present in the ordered and disordered regions of these novel proteins. This study reveals that we should investigate these novel proteins more systematically as they may be important to understand complex diseases.
Development and validation of a next-gen health stratification engine to determine risk for multiple cardiovascular diseases
Authors: Rezaee Mehrdad , Takeh Arsia , Putrenko Igor , Ganna Andrea , Ingelsson Erik
Published: February 2019

Cardiometabolic diseases (CMD) impose greater impact on every aspect of health care than any other disease group. Accurate and in-time risk assessment of individuals for their propensity to develop CMD events is one of the most critical paths in preventing these conditions. The principal objective of the present study is to report the development, and validation of a next generation risk engine to predict CMD. UK Biobank population data was used to derive predictive models for six CMD. Missing data were imputed using imputation algorithms. Cox proportional hazard models were used to estimate annual absolute risk and relative risk of different risk factors for these conditions. In addition to conventional risk factors, the applied model included socioeconomic data, lifestyle factors and comorbidities as predictors of outcomes. In total, 416,936 individuals were included in the analysis. The derived prediction models achieved consistent and moderate-to-high discrimination performance (C-index) for all diseases: coronary artery disease (0.79), hypertension (0.82), type 2 diabetes mellitus (0.87), stroke (0.79), deep vein thrombosis (0.75), and abdominal aortic aneurysm (0.90). These results were consistent across age groups (37-73 years) and showed similar predictive abilities amongst those with pre-existing diabetes or hypertension. Calibration of risk scores showed that there was moderate overestimation of CMD-related conditions only in the highest decile of risk scores for all models. In summary, the newly developed algorithms, based on Cox proportional models, resulted in high disclination and good calibration for several CMD. The integrations of these algorithms on a single platform may have direct clinical impact.
Detecting and quantifying natural selection at two linked loci from time series data of allele frequencies with forward-in-time simulations
Authors: He Zhangyi , Dai Xiaoyang , Beaumont Mark , Yu Feng
Published: February 2019

Recent advances in DNA sequencing techniques have made it possible to monitor genomes in great detail over time. This improvement provides an opportunity for us to study natural selection based on time serial samples of genomes while accounting for genetic recombination effect and local linkage information. Such genomic time series data allow for more accurate estimation of population genetic parameters and hypothesis testing on the recent action of natural selection. In this work, we develop a novel Bayesian statistical framework for inferring natural selection at a pair of linked loci by capitalising on the temporal aspect of DNA data with the additional flexibility of modelling the sampled chromosomes that contain unknown alleles. Our approach is based on a hidden Markov model where the underlying process is a two-locus Wright-Fisher diffusion with selection, which enables us to explicitly model genetic recombination and local linkage. The posterior probability distribution for the selection coefficients is obtained by using the particle marginal Metropolis-Hastings algorithm, which allows us to efficiently calculate the likelihood. We evaluate the performance of our Bayesian inference procedure through extensive simulations, showing that our method can deliver accurate estimates of selection coefficients, and the addition of genetic recombination and local linkage brings about significant improvement in the inference of natural selection. We illustrate the utility of our approach on real data with an application to ancient DNA data associated with white spotting patterns in horses.
The differential distribution of bacteria between cancerous and noncancerous ovarian tissues in situ
Authors: Wang Qi , Zhao Lanbo , Han Lu , Fu Guoxing , Tuo Xiaoqian , Ma Sijia , Li Qing , Wang Yiran , Liang Dongxin , Tang Miaomiao , Sun Chao , Wang Qing , Song Qing , Li Qiling
Published: February 2019

The female upper reproductive tract, including the uterus, fallopian tubes and ovaries, is believed to be a sterile environment. With the improvement of bacterial detection, the theory of the sterile female upper reproductive tract has been frequently challenged in recent years. However, thus far, no researchers have used ovaries as study targets. Six women who were diagnosed with ovarian cancer were included in the cancer group, and ten women who were diagnosed with a noncancerous ovarian condition (including three patients with uterine myoma and seven patients with uterine adenomyosis) were included in the control group. Immunohistochemistry staining using an antibacterial lipopolysaccharide (LPS) antibody was used to confirm the presence of bacteria in the ovarian tissues. In addition, 16S rRNA sequencing was used to compare the differences in the bacteria between ovarian cancer tissues and noncancerous ovarian tissues. BugBase and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) were used to predict the functional composition of the bacteria. Bacterial LPS was present in ovarian cancer tissue and noncancerous ovarian tissue, which implied the presence of bacteria in ovarian tissue. When compared to the noncancerous ovarian bacteria at the phylum level, the cancerous ovarian bacteria were composed of increased Aquificae and Planctomycetes and decreased Crenarchaeota. When predicting metagenomes, gene functions associated with the potentially pathogenic and the oxidative stress-tolerant phenotype were enriched in the ovaries of the cancer group. Forty-six significantly different KEGG pathways existed in the ovarian bacteria of the cancer group compared to that of the control group. Different bacteria compositions were present in cancerous and noncancerous ovarian tissues.

Author summary

Abdominal solid viscera have always been believed to be absolutely sterile. With the improvement of bacterial detection, this concept is being challenged. Researchers found some bacteria existed in endometrial diseases, the question of whether the ovaries are sterile is still unclear. Therefore, we assume that the bacteria in ovarian tissue are associated with ovarian cancer. When compared to the noncancerous ovarian bacteria at the phylum level, the cancerous ovarian bacteria were composed of increased Aquificae and Planctomycetes and decreased Crenarchaeota. When predicting metagenomes, gene functions associated with the potentially pathogenic and the oxidative stress-tolerant phenotype were enriched in the ovaries of the cancer group. Forty-six significantly different KEGG pathways existed in the ovarian bacteria of the cancer group compared to that of the control group. Different bacteria compositions were present in cancerous and noncancerous ovarian tissues.
Exploring HIV infection in a UK vulnerable prisoner population in response to newly identified cases
Authors: Perrett Stephanie E. , Waite Thomas D.
Published: February 2019

Purpose

Prison populations are considered at elevated risk of blood borne virus (BBV) transmission. Between December 2015 and February 2016, four new cases of HIV infection were diagnosed across two male vulnerable prisoner (VP) custodial units in Wales, UK. Cases were identified through routine BBV testing. The paper aims to discuss these issues.

Design/methodology/approach

As a result of identifying four new HIV cases, targeted BBV testing across the VP units using dried blood spot testing for HIV, Hepatitis C (HCV) and Hepatitis B was undertaken.

Findings

A total of 617 men were offered testing, 256 (41 per cent) were tested. No further cases of HIV were identified. Eight men were identified as HCV antibody positive. There was no evidence to suggest the four original cases of HIV were linked.

Practical implications

Embedding universal BBV screening within prison health provision will ensure timely identification of cases. Further research is needed to better understand BBV transmission risks within subsets of the prison population such as the VP and sex offending groups.

Originality/value

Little is known about the prevalence of BBVs in vulnerable prison populations. The findings add to the knowledge available for practitioners in the field.
Case of coincident severe acne and psoriasis in AIDS patient successfully treated with antiretroviral therapy
Authors: Li Yu‐Ye , Dong Rong‐Jing , Cao Li‐Juan , Upadhyay Pratishtha , Kuang Yi‐Qun
Published: February 2019

Cutaneous disorders remain a major problem in HIV‐infected patients, even under antiretroviral therapy (ART). Patients at any stage of HIV/AIDS may suffer from skin lesions. Acnes and psoriasis are both common chronic and inflammatory skin diseases, and the treatment becomes more challenging and complex when combined with HIV infection. Whether the incidence and severity of acne and psoriasis are related to HIV infection is still controversial. Here, we report a rare case of an AIDS patient who developed severe acne along with psoriasis. The patient had initially received multiple systemic and topical antipsoriatic and anti‐acne treatments which failed. Ultimately, he achieved dramatic clinical improvement after initiation of ART for main treatment. An 8‐year follow up demonstrated that the patient has been free of symptoms of both psoriasis and acne till now.
Australian dietitians’ beliefs and attitudes towards weight loss counselling and health at every size counselling for larger‐bodied clients
Authors: Willer Fiona , Hannan‐Jones Mary , Strodl Esben
Published: February 2019

Aim

Research suggests that dietitians now employ weight‐neutral (WN) approaches (Health at Every Size (HAES), Intuitive Eating and non‐diet) as well as more traditional weight‐centric (WC) approaches (weight loss counselling) to address adult weight concerns. This study aimed to compare the knowledge of and attitudes towards WN practice compared with WC practice in Australian dietitians who work with larger‐bodied clients as delineated by practice approach.

Methods

A cross‐sectional web‐based knowledge, attitudes and practices survey was conducted with Australian dietitians who counsel adults with a body mass index >25 kg/m2. Based on their responses, dietitians were categorised into WC (preferring weight loss counselling), WN (preferring HAES counselling) or mixed approach (MA). Between‐group comparisons were conducted using Pearson's chi‐squared tests for knowledge and practice and independent t‐tests for attitudes.

Results

Of the 317 respondents, 18.3% fulfilled the criteria for WN practitioners, 30.3% for WC practitioners and the remainder were classified as providing a MA. Weight‐neutral approaches were more positively regarded generally than WC approaches (84.5% vs 53.9%) as well as considered professionally responsible (86% vs 58.7%) and perceived as more helpful for clients (61.2% vs 35%). Knowledge of WN practice goals was poor with only 36.9% (n = 117) of the participants indicating correctly that this mode of treatment is incompatible with a weight loss goal.

Conclusions

Weight‐neutral practice was considered acceptable by Australian dietetics professionals who counsel larger‐bodied people regardless of their personal practice preference although many displayed inaccurate knowledge of WN approaches.
Foodinformatics: Quantitative Structure‐Property Relationship Modeling of Volatile Organic Compounds in Peppers
Authors: Rojas Cristian , Duchowicz Pablo R. , Castro Eduardo A.
Published: February 2019

The aim of this work was the foodinformatic (chemoinformatic) modeling of volatile organic compounds (VOCs) of different samples of peppers based on a quantitative structure‐property relationship (QSPR) for the retention indices of 273 identified compounds. The experimental retention indices were measured by means of comprehensive two‐dimensional gas chromatography combined with quadrupole‐mass spectrometry (GC × GC/qMS) using the BPX5 and BP20 column coupled system. All the VOCs were represented by means of both conformation‐independent molecular descriptors and molecular fingerprints calculated in the Dragon and PaDEL‐Descriptor software. The dataset was divided into training, validation and test sets of molecules according to the Balanced Subsets Method (BSM). Subsequently, the V‐WSP unsupervised variable reduction method was used to reduce the presence of multicollinearity, redundancy, and noise in the initial pool of 4,336 molecular descriptors and fingerprints. Using this method, a reduced pool of 1,664 was submitted to the supervised selection by means of the replacement method (RM) variable subset selection in order to define a four‐descriptor model. The quality of the model was measured by means of the coefficient of determination and the root‐mean‐square deviation in fitting ( and ), validation ( and ), and prediction ( and ). The negligible differences among the parameters in the three sets indicate a stable and predictive QSPR model. This quantitative structure‐activity relationship was developed keeping in mind the five principles defined by the Organization for Economic Co‐operation and Development (OECD) to make it applicable.

Practical Application

This predictive mathematical model developed from the retention indices of 273 volatile organic compounds (VOCs) detected in pepper samples could be useful for chromatographers working on the identification of other common VOCs in peppers or other foods by means of comprehensive two‐dimensional gas chromatography combined with quadrupole‐mass spectrometry (GC × GC/qMS) using a bi‐dimensional stationary phase coupled system (BPX5 and BP20).
Making use of the social network in conservation genomics: Integrating kinship and network analyses to understand connectivity
Authors: Carroll Emma L. , Gaggiotti Oscar E.
Published: February 2019

Inferring and quantifying recent barriers to connectivity is increasingly important for conservation and management in a world undergoing rapid environmental change. Traditional measures of genetic differentiation can take many generations to reflect a new barrier to connectivity. Although methods that use the linkage disequilibrium signal in mixed genetic samples are able to reflect recent levels of gene flow, they are not suitable for use in situations with low levels of genetic differentiation. Kinship‐based methods, those that assess the spatio‐temporal distribution of related individuals, have been used in this context, but a formal statistical framework for such approaches has been lacking. In this issue of Molecular Ecology Resources, Escoda, et al. adapt the assortativity coefficient, AC, to analyse the networks of kin relationships in the Pyrenean desman (Galemys pyrenaicus) across potential barriers to dispersal. Their modified AC quantifies the proportion of missing kin relationships across putative dispersal barriers with respect to the expected proportion if there was no barrier. This application highlights that AC can be used to test the null hypothesis that a putative barrier has no effect on gene flow, in which case AC is not significantly different from 0. The method represents a useful step forward in conservation genomics by developing and adapting tools to assess contemporary connectivity using genomic data.