dataesr/scientific-paragraphs-categorization huggingface dataset:
Animals with a low call-rate across SNPs (≤0. 95) and pairs of animals with high identity by state (IBS) genotypes based on 2000 autosomal markers (≥0. 95) were also removed from the analysis, as they could be duplicated samples or monozygotic siblings (e. g. identical twins or triplets). This dataset was used for investigation of MAF, heterozygosity, kinship between breeds and estimation of genomic inbreeding. Prior to the LD analysis, SNPs with a MAF lower than 0. 05 were removed. Different sets of SNPs were removed depending on the breed. The proportions of SNPs within categories of MAF are presented in Table  2. In parallel, a second set of QC was performed on the full dataset (all breeds combined). Threshold settings for those QC were the same as those applied for the single breed process, with the exception that the HWE test was not performed, because applying HWE test on a population composed of an ensemble of genetically distinct populations would lead to inappropriate removal of markers.
Genetic relatedness between individuals To understand the genetic relationships between animals within and across breed groups, matrices of genetic distances (D) between the animals were computed from the GRM after the estimation of missing genotypes, as d ij = 1 -g ij if i ≠ j and d ij = 0 if i = j ( where d ij and g ij are the elements of D and GRM, respectively, for animals i and j. Multi-dimensional scaling (MDS) was used to visualize genetic distances between animals for the entire dataset and for each breed separately. The 1% most genetically distant individuals within breed (calculated using the sum of squared distances from all the others animals in the same breed) were removed from the dataset before further analyses, as these genotypes were assumed to be errors of parentage or breed recording.
Genetic maps and linkage analysis The estimation of genetic distances was performed using CRIMAP software  [28]  (v2. 503, modified by J. F Maddox) on the International Mapping Flock (IMF). The IMF is a flock including Texel, Merino, Perendale, Romney and Coopworth sheep breeds over three generations and nine full-sib families, for 127 genotyped animals  [29]. Genetic distances were previously estimated using the IMF with 1000 microsatellites markers  [30]. For the present study, a subset of SNPs approximately evenly spaced along the whole genome was selected. Two SNPs per centiMorgan (cM) were chosen according to their position on the genetic map of Churra sheep  [31]. This SNP distance is about the best resolution that can be achieved with the IMF resource and was assumed to be sufficient for detecting recombination rate changes across a chromosome.
The chromosome specific ratios of genetic over physical distance (used for M2) were obtained by dividing the sum of genetic distances on a chromosome (in cM) by the physical length (in Mb). For M3, the ratios of genetic to physical distances were estimated for each interval on the map. To avoid overestimation, intervals with extreme ratios (≥99. 9 percentile) were removed. Next, the local polynomial fitting method, implemented by the R function loess  [26]  was used to regress the genetic positions of the 6448 SNPs on their physical positions, and to interpolate the genetic positions of the entire Illumina OvineSNP50 BeadChip SNP dataset. The ratio ΔcM/ ΔMb indicates the variation of the estimated recombination rate for each interval between two SNPs and measures the amount of recombination that takes place within a given physical distance on the genome.
Consequently, r 2 values were computed for each pair of SNPs on each chromosome using the function r2fast from the GenABEL R package  [35]. The LD decay curve was obtained using a local polynomial regression of observed pairwise r 2 values on genomic distances for a randomly selected sample of 20,000 marker pairs for each chromosome. This process was repeated 30 times to avoid sampling artefacts, and means and variances over repetitions and chromosomes at 2000 values equally spaced between 0. 5 cM to 50 cM were estimated. Finally, the LD decay per breed was considered as the mean of the expected r 2 (from the local polynomial regression) over each of the 26 chromosomes, estimated per chromosome at each of the 2000 genetic distances, weighted by the inverse of the variances previously estimated on the 30 repetitions.
e. 18 for Romney and 12 for Texel), which were selected as 100% purebred animals, which could explain the lower H e observed by Kijas et al. [4]  compared to the results reported here. The high number of polymorphic SNPs observed in this study is similar to estimates observed for a different and smaller dataset for a variety of worldwide breeds  [4]. However, the SNPs selected to be included in the Illumina OvineSNP50 BeadChip have MAF greater than 0. 25 and, therefore, ascertainment bias could have been introduced  [4]. This potential ascertainment bias was previously investigated in Kijas et al. [40] , who concluded that it is unlikely that estimates of genetic diversity between breeds and regions can be strongly modified by ascertainment bias, as a variety of breeds were used for SNP detection and SNP chip panel development.
Acknowledgments We would like to sincerely thank  Ovita Limited  (a consortium between AgResearch Ltd. and  Beef + Lamb New Zealand ) for funding this research, and for providing the genotypes. Animals genotyped were recorded in Sheep Improvement Limited (SIL) and owned by breeders. We gratefully acknowledge them for allowing access to their animal resources. Furthermore, we are extremely grateful to the  International Sheep Genomics Consortium  for generation of the  Illumina OvineSNP50 BeadChip  and the  AgResearch animal genomics field and laboratory  staff for collecting the DNA, genotyping the animals and performing the initial quality checks of the genotypes that were used in this study.
Study population and mutation detection design Cases and controls were selected from two multicentre studies: one conducted in South America (LA study) between 1998 and 2002 and the second between 2002 and 2005 in Europe (ARCAGE study), from which biological samples were available in the IARC biorepository, along with complete epidemiological data. Extensive details on data and sample collection from these studies are included elsewhere  [41] [42] [43]. Briefly, all subjects underwent personal interviews to collect information on lifestyle exposures and hospital records were reviewed to obtain clinical and pathological information  [41, 42]. Centralized HPV testing was completed for both studies determined on serology testing as described before  [44]. HPV positivity was defined based on HPV16 E6 status, which has been shown to be a highly sensitive and specific marker of HPV16-related oropharyngeal tumours  [43, 45, 46].
Informed consent was obtained from all participants in the two studies, and the analysis was approved by the Ethical Review Committee of the International Agency for Research on Cancer. In order to test the targeted ctDNA detection approach, we selected 36 HNSCC fresh tumor samples, including 14 early (stage I and II) cases, from the ARCAGE study with available matched plasma samples. Oral rinses were not collected as part of the ARCAGE study  [41]. DNA from 36 HNSCC tumors had been previously sequenced and found to carry 65 mutations in 5 genes (TP53, NOTCH1, CDKN2A, CASP8, PTEN) from a panel of the 14 most frequently mutated genes (CASP8, CDKN2A, FAT1, FBXW7, HRAS, IRF6, MLL2, NOTCH1, NSD1, PTEN, PIK3CA, RB1, TP53, TP63) (unpublished results). Gene selection was based on an independent analysis of TCGA data on HNSCC using MutsigCV algorithm complemented with the list of the most frequently mutated genes reported in the literature.
Sequencing data analyses and validation of detected mutations For the calling of variants, we used Needlestack, an ultra-sensitive variant caller, which estimates the distribution of sequencing errors across multiple samples to reliably identify variants present in very low proportion (https://github. com/IARCbioinfo/needlestack). A detail description of the Needlestack variant caller has been previously published  [18, 48]. Variant calls were annotated using ANNOVAR  [49]  and only TP53 mutations reported in COSMIC-76 that were indels, nonsense, splicing, or missense variants reported as deleterious in SIFT or Polyphen, were kept for subsequent analyses. OncoPrinter and MutationMapper tools were used for visualization of mutational data  [50, 51].
Statistical analyses Survival data was available for all 36 ARCAGE cases. Overall survival was calculated from cancer diagnosis to death for any cause or end of follow up (last follow up date: 30/01/2013). Follow-up was censored at 5 years, given that most cancer related events occur before that time. The Kaplan-Meier estimator was used to estimate the distribution of the 5-year survival. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HRs) and their corresponding p values for ctDNA mutation presence using age, subsite, stage, smoking and alcohol status as covariates. Logrank test was used to compare the different survival distributions. Clinical characteristics were compared between tumor samples with and without detectable TP53 mutations with Fisher's exact test.
ACKNOWLEDGMENTS The authors wish to acknowledge  Dr. Felipe Vaca  for his valuable collaboration in the standardization of the targeted sequencing assays for the ARCAGE cases and  Valérie Gaborieau  for her contribution in database curation and data homogenization. The authors acknowledge all patients who donated their biological specimens. This work was undertaken during the tenure of a Postdoctoral Fellowship to  Dr Sandra Perdomo  and to  Dr Patrice Avogbe  from The  International Agency for Research on Cancer , partially supported by the  European Commission FP7 Marie Curie Actions -People -Co -funding of regional, national and international programmes (COFUND).
Participants and study design We included consecutive women aged 18 to 45 years with the first confirmed episode of VTE referred to the outpatient clinic of our Hemostasis Unit (Hotel-Dieu Hospital, Paris, France) between January 1, 2000, and December 31, 2009. Women were excluded if they: presented with central retinal vein obstructions or cancerrelated VTE; were on a progestin only contraceptive (POC) (n = 71); or did not remember which contraceptive they used at time of VTE (n = 41). For all women included, data were collected at the time of their first visit at the Hemostasis Unit. A cross-sectional analysis of the clinical and biological characteristics was first performed. Cases of DVT, PE, and CVT were diagnosed with an appropriate imaging procedure. [13] PE was defined as the presence of a positive computed tomographic pulmonary angiography or a high-probability ventilation/perfusion lungscintigraphy.
DVT was diagnosed by use of compression ultrasonography or venography. DVT of a calf vein was considered as distal, and DVT involving the remaining vein segment (popliteal, femoral, or iliac) was considered as proximal. [13] CVT was diagnosed by positive cerebral MRI. The presence of the following transient risk factors was recorded: surgery (last 3 months before VTE), plaster cast, prolonged bed rest (≥4 days), hormonal contraceptive use, pregnancy, early postpartum period (6 weeks), venous sclerosis, or lengthy air travel. Caesareans were counted in the surgery group. The characteristics of women were extracted from their medical charts using a standardized questionnaire which was completed during a medical consultation by a physician at the Hemostasis Unit. Data included information on medical history, use of all treatments, family history, reproductive factors, other factors such as height and weight, smoking status, the use of exogenous hormones, and the first VTE event.
Statistical analysis Baseline characteristics were analyzed with the classic statistical tests for cross-sectional data: mean ± standard deviation (SD) for continuous variables and proportions for categorical variables. To compare qualitative variables, the chi-square test was used. T-test or Variance analysis were performed to compare quantitative variables among groups. Statistical significance was associated with a 2-tailed P-value below. 05. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated by logistic regression. Statistical analysis used procedures available in SAS software (SAS Institute, Inc, Cary, NC).
Results A total of 3009 consecutive premenopausal women with the first VTE were included in the COREVE study. Data were collected during the 1st visit at the Hemostasis Unit with a median time since VTE of 9 months. Among these women, 2088 (69. 4%) used CHC and 921 (30. 6%) were nonusers at the time of their first VTE. Table  1  shows the clinical and biological characteristics of the women included (CHC users and nonusers). CHC users were significantly younger and leaner compared with the nonusers (respectively [mean ± SD] 29. 0 ± 7. 2, 31. 6 ± 7. 1 years old, and 23. 0 ± 4. 4, 23. 9 ± 4. 8 kg/m 2 ). There was no difference in VTE family history between the 2 groups. CHC users had significantly less history of deliveries than the nonusers, even after the age adjustment. Biological thrombophilia screening was performed after the first VTE.
Acknowledgments: We thank  D. Chatain ,  R. V. Zucker , and  R. Bergamaschini  for the discussions about the experimental results and theoretical PF simulations and  V. Mondiali  for the useful discussions on EBL and nanoimprinting fabrications. Funding: We acknowledge the projects  PHC Maghreb  (no. 32595SL ),  EMMAG-Erasmus Mundus Maghreb and Egypte , the  Nanotecmat Platform of the IM2NP Institute of Marseille , and the  CP2M microscopy center of the Aix-Marseille University  for the availability of the tools and the equipment needed for this study. M. S. acknowledges the support of the  Postdoctoral Research Fellowship  awarded by the  Alexander von Humboldt Foundation. The computational resources for PF simulations were provided by  Zentrum für Informationsdienste und Hochleistungsrechnen at Technische Universität Dresden  and by the  Jülich Supercomputing Centre  within the project no.
K. ) was detected by immunohistochemistry according to standard techniques. The rabbit anti-ATP6ap2 (Sigma HPA003156) was validated previously  25. Briefly, microwave antigen retrieval was performed in 10 mM sodium citrate buffer (pH6. 0) and the rabbit anti-ATP6ap2 or the rabbit anti-Ki67 antisera was diluted at 1/500 in PBS containing 0. 05% Tween-20. Then sections were blocked with 10% normal horse serum and 0. 3% triton X-100. For ATP6ap2 immunostaining, detection of primary antibody was achieved by incubating sections during 1 hour at room temperature with Alexa Fluor 555-conjugated secondary antibody (1:500, Invitrogen Molecular Probes). The sections were mounted with Mowiol 4-88 mounting medium (Citifluor) containing DAPI (5 μg/ml). For Ki67 immunostaining, the signal was amplified using the ABC method (Vector Laboratories, Burlingame, U.
10 6 WT B6 SJL (CD45. 1)/2. 10 6 Atp6ap2 RosaTAM (CD45. 2). Chimeras were kept throughout the experiment on antibiotic-containing water (0. 2% Bactrim, Roche, Germany). 8 weeks after reconstitution, the level of blood chimerism was determined by FACS. At that time, >99% of blood B cells were of donor origin. Flow Cytometry. Antibodies used are listed in Suppl. Table  S1. Before staining, cells were pre-incubated 10 min on ice with the 2. 4G2 antibody to block Fc receptors. In all experiment, Sytox Blue (Invitrogen) was used to exclude dead cells from the analysis. Multiparameter FACS acquisition was performed on a LSRII SORP system (BD Biosciences). Analysis was performed using FACSDiva 8. 01 (BD Biosciences) software. Doublets were systematically excluded based on side scatter (SSC) and forward scatter (FSC) parameters.
Acknowledgments We thank the  Bloomington Drosophila Stock Center  ( NIH P40OD018537 ),  NIG-fly facility ,  VDRC Stock Center and Harvard Medical School  ( NIH/NIGMS   R01-GM084947 ), for providing the transgenic RNAi fly stocks used in this study;  E. Knust  for the gift of the anti-myosin V antibody,  R. Renkawitz-Pohl ,  A. Ephrussi ,  B. Loppin ,  D. McKearin ,  D St Johnston  for fly stocks,  M. Billaud  for hLKB1 cDNAs and  T. David  for the drawings. This work was supported by the  ATIP-Avenir program , the  Association pour la Recherche Contre le Cancer  and the  Region Auvergne.
The sponge explants were enclosed in the meshes (Supplementary Materials Figure  S2F ). method, composed of 10 cm × 10 cm travertine tiles anchored to the ropes and the rope drilled into the corner of rocky tablets. The sponge explants were pasted on each tile using a non-toxic underwater bi-component epoxy putty (SubCoat, Veneziani Yacht Systems, Italy) (Supplementary Materials Figure  S2E ); (ii) nylon mesh method, made of a posh-like net with 2 cm meshes fixed to ropes. The sponge explants were enclosed in the meshes (Supplementary Materials Figure  S2F ). The abiotic sea parameters were obtained by the multiparameter probe 'Idronaut' in the Portofino Promontory area from 0 to 35 m (Povero pers. comm. ). At both the Liguria and Sardinia sites, water temperatures were recorded by means of an underwater HOBO ® Data Logger (Onset, MA, USA) installed in the plants and in the wild.
Temperature and Light Experiment This first experiment was performed in November 2013, using a running seawater flow rate of 2 L•min -1. The five following treatments were implemented: (i) control (T = 16 °C; natural light cycle), (ii) light 24/24 h (300 lux), (iii) dark 24/24 h (0 lux), (iv) 14 °C, and (v) 20 °C. The collection of sponge specimens was performed after 0, 7 and 30 days, in each aquarium and in triplicate. Water temperature and light intensity were recorded in all aquaria by means of an underwater HOBO ® Data Logger (Onset, MA, USA). The probes were set to record temperature 2 times per day (every 12 h). The abiotic sea parameters were obtained by the multiparameter probe 'Idronaut' in the Portofino Promontory area from 0 to 35 m (Povero pers. comm. ). At both the Liguria and Sardinia sites, water temperatures were recorded by means of an underwater HOBO ® Data Logger (Onset, MA, USA) installed in the plants and in the wild.
Temperature and Light Experiment This first experiment was performed in November 2013, using a running seawater flow rate of 2 L•min -1. The five following treatments were implemented: (i) control (T = 16 • C; natural light cycle), (ii) light 24/24 h (300 lux), (iii) dark 24/24 h (0 lux), (iv) 14 • C, and (v) 20 • C. The collection of sponge specimens was performed after 0, 7 and 30 days, in each aquarium and in triplicate. Water temperature and light intensity were recorded in all aquaria by means of an underwater HOBO ® Data Logger (Onset, MA, USA). The probes were set to record temperature 2 times per day (every 12 h).
UHPLC-HRMS analysis Prior to the UHPLC-HRMS analysis, all samples were solubilized in 1 mL of MeOH and were diluted 1/1000. In addition, five Quality Control (QC) samples were prepared by combining 10 µL of each sample in a 2 mL vial and these pools were injected every seven samples to allow chromatogram alignment during data treatment. In-line UHPLC-UV-HRMS analysis was performed using a Dionex system Ultimate 3000 equipped with an autosampler and a Dionex Ultimate 3000 diode array detector (210 and 280 nm detection), connected to a qToF mass spectrometer with an electrospray ionization interface (Bruker Impact II). Mass spectra were recorded in the positive mode. UHPLC separation was achieved on an analytical Nucleodur PolarTec column (100 × 2 mm, 1. 8 µm, Macherey Nagel) using a linear elution gradient of H 2 O/CH 3 CN/formic acid to which was added 10 mM of ammonium formate from 80:20:0.
1 (v/v/v, isocratic from 0 to 2 min) to 40:60:0. 1 (v/v/v, isocratic from 8 to 10 min), at a flow rate 0. 45 mL•min -1 for a total of 14 min. The injected volume was set at 10 µL and detection at 280 nm. The mass spectrometer analyzer parameters were set as follows: nebulizer sheath gas, N 2 (2. 1 bar); dry gas, N 2 (8 L/min); capillary temperature, 200 • C; capillary voltage, 2500 V; end plate offset, 500 V; collision gas, He; collision energy, 4 eV. Data were acquired in the 50 to 1200 m/z range.
UHPLC-HRMS data processing for untargeted analyses Following UHPLC-ESI-HRMS data acquisition, MS chromatograms (Base Peak chromatogram-BPC) were exported as line spectra and converted into the netCDF file format to process the data in centroid mode with XCMS  [48]  using R software (version 3. 2. 2. ). The XCMS approach involved several steps necessary to generate a final matrix: (1) Peack picking (peakwidth = c  (2, 20) , ppm = 10) without threshold prefilter  [49] , (2) retention time correction (method = "obiwarp"), (  3 ) grouping (bw = 10, minfrac = 0. 3, minsamp = 1), (4) Fillpeaks using a parameter of "noise level" that sets the minimum intensity for a centroid data point to be considered as part of a peak (noise level = 10 3 ), and finally  (5)  report and data matrix generation (ions/Retention time × sample) that was exported using Microsoft Excel.
The theoretical m/z values for typical adduct species were compared with the experimental values to ensure the identification of the compounds (once per treatment and fraction and once for the QC samples). For spectra presenting multiple adducts, we summed the area of all adducts to obtain the total intensity corresponding to one compound. Analytical blanks confirmed that no memory effects or sample contamination skewed results. The concentration of the metabolites was assessed using a calibration with standards of crambescidin-816 and crambescin-A2-462, assuming all compounds of the same family had similar ionization potential. One-way ANOVA was performed on the data to investigate the statistical differences between conditions.
Acknowledgments: This study was funded by European funding within the  BAMMBO  project ( H2020 , www. bammbo. orgsustainable production of  Biologically Active Marine Metabolite Based Origin ). We warmly thank  Ornella Passafiume  ( OOV ) for her help with the nutrient analysis as well as  Fabio Damiano Ledda  and  Andrea Padiglia  ( University of Sassari ) for their participation with the mariculture. We also acknowledge  David Luquet  and  EMBRC  for the collection of sponge specimens and their maintenance in aquaria at the OOV. The metabolomics study was supported by the  MALLABAR platform (Marseille, France).
Numerous related genomes were already deposited in databanks over the past 10 years, but most of them were from mesophilic strains and very few from psychrotolerant and thermotolerant strains. Psychrotolerance determines the capacity of bacteria to potentially lead to food poisoning after ingestion of contaminated cold-stored products. High-quality genomic DNA was obtained from purified isolates of each strain and used to generate Illumina libraries with a 350-bp insert gel size selection, according to an improved Fasteris de novo protocol (Fasteris SA, Plan-les-Ouates, Switzerland). An additional library was obtained for four strains using the Illumina Nextera Mate-Pair (3-kb insert gel size selection). Libraries were sequenced using HiSeq high-output DNA sequencing with paired-end reads of 2 ϫ 100 bp and a final average sequence coverage of 130ϫ.
ACKNOWLEDGMENTS This work was funded by  ANR   PathoBactEvol  project number  ANR-12-ADAP-0018. We thank the many collaborators who contributed to provide strains:  L. M. Wijnands  ( RIVM, The Netherlands ),  S. Scherer  ( TUM, Germany ),  P. E. Granum  ( NVH, Norway ),  A. Christiansson  ( SDA, Sweden ),  C. Nielsen-LeRoux  ( INRA, Jouy-en Josas, France ),  C. Denis  ( ADRIA, France ), and  S. Herbin  ( ANSES, France ). We are grateful to  Fasteris SA  for its contribution to the sequencing experiments.