dataesr/scientific-paragraphs-categorization huggingface dataset:
As such, studying selection signatures in livestock offers a valuable approach to identify genes and polymorphisms that underlie variation in these traits. The power to detect such signatures depends on two things: sample size (both of the number of individuals and populations included in the studies) and marker density  [1]. As datasets become larger, it should be possible to generate evolutionary hypotheses on the history of selection signatures. In this work, we exploited a large sheep dataset in a relatively small geographic area (France) to this goal. Sheep, one of the first domesticated species, originated from a population of Ovis orientalis in the fertile crescent in contemporary Iran  [2, 3]. From its domestication centre, sheep eventually spread world-wide, adapting to a large range of environmental conditions.
In agriculture, sheep are raised for meat, wool and milk products, with commercial breeds usually specialised for one type of production. This history has shaped sheep genetic diversity and makes it an interesting model species to study the evolution of populations under adaptive constraints  [4, 5]. In a recent study, the International Sheep Genomics Consortium (ISGC)  [6]  compiled a dataset of DNA samples from 74 populations of sheep from around the world genotyped for approximately 50,000 SNP markers: the Sheep HapMap dataset (http://www. sheephapmap. org/). Analyses of this dataset showed both clear geographical structure of breeds and strong admixture among breeds. In Western Europe, geographical structure was clear with several population groups identified that corresponded to their area of origin: Italian, Iberian, Swiss, British and Northern European groups  [6].
Only one French sheep population, the Lacaune breed, was included in this study. It clustered in the Iberian group, consistent with its origin from the south-western region of France. Besides the Lacaune breed, France harbours many other different sheep breeds across the country and because of its geographical position, France borders many of the geographic areas associated with western European sheep population groups of the Sheep HapMap dataset. The study of French sheep diversity should therefore provide valuable insights on the establishment of genetic structure in European sheep, and in particular inform us on the history of sheep husbandry in Europe. French sheep diversity was recently studied with the genotyping of 21 microsatellites in sheep from 49 breeds  [7]. This study confirmed that French sheep breeds show a structure consistent with influences from both northern European, specifically British breeds, and southern European breeds.
Hence, French sheep populations are likely to harbour a large part of European sheep diversity in a relatively small geographical region, offering a powerful model for the study of adaptation. Several studies have identified signatures of selection in sheep: signatures associated with pigmentation  [8] , fat deposition  [9] , milk yield  [10] , adaptations to climate  [5, 11]  and resistance to parasites  [12]. There have also been studies looking at a number of breeds: a study which included only American breeds of sheep  [13]  and two studies including sheep populations from around the world  [6, 14]. These world-wide studies, which used data from the ISGC Sheep HapMap data set, detected signatures containing genes or QTLs associated with pigmentation, morphology, muscling, milk production and wool quality.
Studying data sets with many different breeds also allows the study of diversity in selection, the different mutations and genes selected on to reach the same phenotype (ie. colour, muscling etc. ). All of these studies however, relied on medium density genotyping using about 50,000 SNP markers. This limits the precision of localization of candidate genes underlying selection signatures as well as the identification of potential haplotypes carrying causal mutations. The present study aims to enhance our understanding of the mechanisms of adaptation in livestock by providing and analysing a large data set of high density genotyping (around 600,000 SNP markers) in 542 samples from 27 French sheep populations. Our analyses of the genetic structure in this dataset identify clearly two main origins of breeds and show how these breeds complement the Sheep HapMap dataset.
French sheep data A total of 691 French sheep were genotyped for 653,305 autosomal SNPs (Illumina Ovine Infinium® HD SNP BeadChip) with 27 sheep breeds being represented in this study. The populations chosen represent the majority of commercial breeds present in France but also included some breeds maintained for conservation purposes. Breed names and their abbreviations are listed in Table  1. In each breed, genotyped animals were chosen so as to be as unrelated as possible based on pedigree records. DNA samples from this study came from various French flocks. Blood sampling was not performed specifically for this study. Blood samples were taken from commercial farms. Animals did not belong to any experimental design but were sampled by veterinarians and/or under veterinarian supervision for routine veterinary care.
Analysis of population structure Three methods were used to study population structure from SNP genotypes: a principal components analysis to visualize patterns in relationships between individuals using PLINK based on the genotype matrix  [15, 16] ; a model based approach to estimate individual ancestry coefficients, using the software sNMF  [19] ; a model based approach to infer populations splits and mixtures using the software treemix  [20]. We included two outgroup populations in our analyses: Asian Mouflon (Ovis orientalis orientalis) and European Mouflon (Ovis aries). Summary statistics including allele frequencies from 19 Asian Mouflon were generated and provided by the NextGen consortium (http://nextgen. epfl. ch/), as per the NextGen consortium data sharing agreement. The allele frequencies were used to root the population tree in the maximum likelihood tree analyses.
The number of migration events included in the population tree was chosen based on the comparison of the fraction of the variance in relatedness between populations that is accounted for by the model, as explained in the software documentation (Additional file 2). To study French sheep population structure within other European breeds, a subset of breeds from the Sheep HapMap data set were included in population structure analyses; and both model based approaches, estimation of individual ancestry coefficients and inferred population splits and mixtures. The Sheep Hap-Map individuals included in this study were the same European sheep used by Fariello et al. [14]  including breeds from; Central Europe; Southwestern Europe; North Europe; and Italy. Breeds were removed if they had a sample size smaller than 20, were a result of recent admixture or had recently experienced a severe bottleneck  [14].
Shared markers between the French sheep breeds and the Sheep HapMap subset of breeds, 39,976 SNPs, were used to estimate individual ancestry coefficients using sNMF  [19]. The same Iranian Asian Mouflon sheep were included in the analysis to root the population tree when estimating population splits and mixtures using treemix  [20]  where allele frequencies from 30 Iranian Asian Mouflon sheep from the NextGen project were included to root the population tree. For the combination of our dataset with the Sheep HapMap FLK and hapFLK genome scans FLK  [23]  and hapFLK  [24]  tests were used to detect signatures of selection. Both tests are aimed at identifying regions of outlying differentiation between populations while accounting for their hierarchical structure. The evolutionary model underlying FLK and hapFLK assumes that SNPs were polymorphic in an ancestral population.
In order to consider only SNPs matching this hypothesis, SNPs with estimated ancestral minor allele frequency < 5% were removed, leaving 465 2351 SNPs for use in the analyses. For the FLK analysis, significant SNPs within 1 Mbp from each other where grouped into a common selection signature (FDR 1%). To verify that grouping SNPs within 1 Mbp is appropriate we estimated LD decay in a subset of all populations in our dataset averaged over chromosomes (Additional file 3). Candidate genes were identified in regions containing 10 or more significant SNPs. For hapFLK, the number of haplotype clusters has to be specified in order to fit the Scheet and Stephens  [25]  model. This number was set to 30, from results obtained using the cross validation procedure included in the fastPHASE software  [25].
Sequencing reactions were carried out via the BigDye® Terminator v3. 1 Cycle Sequencing Kit (http://www. appliedbiosystems. com). The primers are listed in Additional file 5. Sequences from three animals from each breed exhibiting a selection signature were aligned against scaffold 00839 of the Ovis aries musimon assembly (GenBank accession HG925721. 1), which we found of better quality than the OAR3. 1 reference genome, using CLC software and allowed the detection of polymorphisms. The discovered polymorphisms were genotyped for all the animals of the relevant breeds by sequencing purified PCR products with internal primers using the same protocol. The sheep genome browser from EBI (www. ensembl. org) was used to determine conserved regions through 39 eutherian mammals and calculate GERP scores.
Population structure of European sheep To place the population structure of French sheep into the context of European population diversity, population trees with mixture events and individual ancestry coefficients were estimated using European sheep breeds from the Sheep HapMap project and included the French dataset downscaled to medium density SNP information. The maximum likelihood population tree with no migration events (Fig. 2 ) showed that French sheep complemented the Sheep HapMap dataset in the European sheep population tree. Most of the breeds in our dataset added to the global diversity, as they tended to root in internal branches of the population tree, either within northern or southern breeds (e. g. the Berrichon du Cher/Île de France and Causse du Lot/Rava/Limousine respectively) or at the basis of the population tree (e.
Additional polymorphism discovery and large-scale genotyping at MC1R locus Our analysis revealed that selection in the region encompassing the MC1R gene, a gene associated with pigmentation, affected the only three black-faced breeds in our dataset: the Romanov, the Suffolk and the Noire du Velay (Fig. 4a, b ). Furthermore, haplotype diversity plots showed they were selected on different haplotypes (Fig. 4b ). To test whether these three breeds were selected not only on different haplotypes but also on different mutations in MC1R we re-sequenced individuals from these breeds as well as a breed not found to be selected on in this region, the Texel. Sequencing of 6894 bp of the MC1R region and genotyping of the Noire du Velay, Romanov, Suffolk and Texel breeds allowed us to generate a reference sequence (EMBL accession number LT594967) with 2 remaining N blocks of 270 and 261 nucleotides in the 5′ region.
It exhibits a unique open reading frame. We identified a potential TATA box with a "TATAAA" motif (at positions 14,229,176-14,229,181), 2522 bp before the start codon and a potential polyadenylation signal "AATAAA" (at positions 14,233,015-14,233,020). Therefore we can assume that the 5'UTR of the sheep MC1R transcript is about 2500 bp long and the 3'UTR around 500 bp long. The deduced MC1R sheep protein is 317 amino acids. Our sequences allowed us to detect and further genotype six SNPs and one 11 bp insertion (Fig. 4c ) (dbSNP accession numbers ss# 1996900605 to 1996900611). We found that the three breeds were indeed almost completely fixed around MC1R, and that the three main breed haplotypes were different. The Noire du Velay resequenced individuals were all homozygous in the region and carriers of the two known mutations for dominant black in sheep.
French sheep populations and the meeting of European sheep domestication routes Our dataset provided a new sample of populations from European sheep that we have shown to complement the already available samples from the Sheep HapMap project. Our analysis of population structure in French, and more generally European sheep, highlighted how populations have been established in the continent since sheep domestication. In domesticated samples, the three methodological approaches we used showed a clear structure (Fig. 1 ) in two main groups of breeds plus two highly differentiated breeds, the Ouessant (also called Ushant) sheep and the Mérinos de Rambouillet. The Ouessant sheep breed has historically been isolated and consequently has accumulated substantial drift. Its position in the tree is consistent with it having a distant origin from the other breeds in the data set.
The Ouessant breed possibly originated from a first wave of colonization after domestication, as has been shown for other ancient European breeds of sheep such as the Soay sheep  [31]. However, its positioning in the population tree might not be very reliable due its long branch length. The other highly inbred breed is the Mérinos de Rambouillet. This breed consists of a single flock of animals that has been raised without the introduction of additional animals since 1786. Although it has a very long branch in the population tree, it clusters with the other Merino population in the dataset, the Mérinos d' Arles. Apart from the Ouessant and Mérinos de Rambouillet, the populations were divided into two main groups, corresponding to northern and southern origins (Figs. 1  and 2 ). The two groups present contrasting structure.
However, this is difficult to confirm because the main British breeds involved, the Leicester Longwool and Southdown, are not part of our dataset nor of the Sheep HapMap dataset. Finally, the migration branch from the Île de France to Mourerous breed was an unexpected result and might be due to some purported recent crossing of northern breeds with Mourerous sheep to improve meat production. Overall, the pattern of genetic diversity that emerges from our analysis is that of three main lineages for the European populations, an ancestral lineage that is found today in the Ouessant, the Romanov and the Soay breeds and two largely separated geographical lineages (north and south) of modern domestic sheep, with evidence for punctual admixture events between northern and southern populations. It is tempting to relate these two main lineages to the two known domestication routes (Danubian and Mediterranean), but further studies are needed to formally test this hypothesis, possibly exploiting ancient DNA information.
e. low differentiation due to general selection on the same haplotype). Only a few northern breeds had some more elevated haplotype diversity, which allowed detecting selection when included with the southern breed. Interestingly, the selection signature in this region looked quite widespread for the same haplotype in most of the breeds in the dataset. These three cases illustrate how increasing the number of populations interrogated in genome scans for selection can increase detection power. In our case however, the few selection signatures detected that are due to differential selection between the two groups show that drift, i. e. independent evolutionary history between the northern and southern groups, still remains the most parsimonious explanation for their genetic differences. It is still possible that adaptive effects that were undetected in our analysis have contributed to these differences.
Keratinocytes can then incorporate melanin  [65]. For example, it has been shown in a study of Asiatic sheep that black individuals had only eumelanin present in their wool  [66]. Our analysis revealed that selection in this region affected the only three black-faced breeds in our dataset: the Romanov, the Suffolk and the Noire du Velay. Furthermore, haplotype diversity plots showed they were clearly selected on different haplotypes (Fig. 4a, b ). When we re-sequenced individuals from these breeds as well as a breed not found to be selected in this region, Texel, we found that the 5'UTR of the sheep MC1R transcript is about 2500 bp long and the 3'UTR around 500 bp long. Few data are present for mammalian 5'UTR of MC1R transcripts however the NM_002386. 3 human transcript also shows a long 5'UTR (1380 bp) and a 766 bp 3'UTR.
Consistent with the SNP array analysis, the three selected breeds showed almost no between individual variation within breeds, and carried completely different sets of mutations. Assuming MC1R is the causative gene, which seems highly likely given the large literature on its effect on coat colour, our results would indicate that only in the Noire du Velay breed coding sequence variants can be the causative mutations. In the two other breeds, regulatory variants are involved, possibly SNP rs406233740 in the Suffolk. CAVIAR results confirmed allelic heterogeneity and indicated six independent SNPs under selection in the study's population. Two other examples of multiple adaptive alleles in this dataset were found at the RXFP2 and SOCS2 genes. The Relaxin-like receptor 2 (RXFP2) gene has been associated with the presence/absence of horns as well as horn development in different breeds of sheep and is therefore already known for its heterogeneity.
In Soay sheep, horn type (horns or scurs) and horn length was associated with the same region on chromosome 10 which was mapped to a single candidate gene, RXFP2  [69]. Later, a single SNP was found to be highly predictive for horns (dominant when inherited maternally) in Australian Merino sheep on chromosome 10  [70]. A synonymous mutation, p. P375 (c. 1125A > G) in Tan and Suffolk sheep was found to be associated with the appearance or absence of horns  [71]. When comparing horned and polled animals from seven Swiss breeds of sheep a 1833 bp insertion in a 4 Kb region at the 3 prime end of RXFP2 was found only in polled animals  [72]. Finally, the RXPF2 region was detected as a signature of selection in different population groups of the Sheep HapMap dataset  [6, 14]. The haplotype cluster frequency plots from those breeds under selection highlighted the complexity of selection in this region.
The signal in our study was detected in all (page 28 of Additional file 8) and separate analyses of northern and southern sheep with the two most significant SNPs in the southern analyses within RXFP2 (both intronic mutations) while the signal from hapFLK results of northern sheep peaked 89 Kb before the gene. None of the northern breeds included in our dataset are horned, and the reason for detecting a signature here is because different haplotypes have been selected on within this region. When we looked at the region extending 100 Kb on either side of RXFP2, while the SNP frequencies within the gene were similar among northern sheep and other polled southern sheep, in the 100 Kb before the gene there were four distinct haplotypes in polled French sheep. The software CAVIAR detected 10 independent SNPs in this region.
Conclusion In this study, we highlight the ability of selection signature studies to retrace the history of selected alleles through the use of large datasets (many individuals from many populations) and high density DNA marker information. The dataset used in this study, high density SNP genotyping of many French sheep breeds, was a powerful tool for studying adaptation and selection. We showed that French sheep populations harbour great genetic diversity, with influences from both southern and northern Europe. We detected a large set of selection signatures that we expect will foster new research on studying effects of variation of these genes on phenotypes and shed light on the history of sheep domestication and breeding in Europe. In particular, we identified selection hotspots seen in many species, introgression of adaptive alleles, and allelic heterogeneity.
We identified allelic heterogeneity using a quantitative approach and confirmed the presence of allelic heterogeneity in a selection signature containing the candidate gene MC1R by resequencing that region in the breeds under selection. Future studies with the focus on the history of selection can be ameliorated with the use of whole genome sequencing, because sequences would contain the causal adaptive mutations, and also by including ancient DNA from past populations. Finally, we believe that the combination of this dataset with others likely to come, offers great prospects to decipher the history of animal domestication, and its relation to the human neolithic expansion.
Acknowledgements We deeply appreciated the involvement of various breeding organizations for their assistance in sample collection (France Génétique Elevage http://en. francegenetique-elevage. org/, FranceAgriMer http://www. franceagrimer. fr/,le Groupement des Moutons d'Ouessant http://www. moutons-ouessant. com and l'Institut de l'Élevage  (http://idele. fr),especially  Coralie Danchin  as coordinator of the  GenImpact program. Finally, we thank  Julie Demars  for the European mouflon samples,  François Pompanon  for providing the Asian Mouflon allele frequencies and LABOGENA (http://www. labogena. fr/),especially  Julie Ogereau  and  Bérengère Camus , for the genotyping using  Illumina Ovine Infinium® HD SNP Beadchips.
Funding CMR benefited from a joint grant from the  European Commission  and the  Swedish University of Agricultural Sciences , within the framework of the  Erasmus Mundus joint doctorate "EGS-ABG ". This work was funded by the  Animal Genetics division  from the  French National Institute for Agricultural Research (INRA) , the  European 7th Framework Programme  ( 3SR  project) and the CORAM members ( OPA project lead by Jérôme Raoul ). The biological samples for the Merinos de Rambouillet were obtained thanks to the  CRB-Anim infrastructure ,  ANR-11-INBS-0003 , funded by the  French National Research Agency  in the frame of the ' Investing for the Future' program. The funders had no role in study design, and analysis, decision to publish, or preparation of the manuscript.
Human-Computer Interaction with IoT The US National Intelligence Council defined the Internet of Things (IoT) as one of the six most "Disruptive Civil Technologies"  [2]. The European Community is investing 192 million of euros in several different domains of IoT research through the Horizon 2020 programme for the years 2014-2017  [13]. Since the first definition of IoT, different technological platforms generated different related visions of what the IoT is. Atzori et al. identified three main visions: the first one is more "thingsoriented" and respond to the initial trend of equipping everyday objects with RFID tags; the second vision, "Internet-oriented", relies on smarter objects, capable of fulfilling the full Internet Protocol (IP) stack; the third vision of IoT highlights the semantic reasoning that can be performed on IoT data  [2].
Performing the queries on full text of the three aforementioned databases, we obtained 56 distinct results for Q1 and 29 distinct results for Q2. After removing duplicated papers obtained by different databases, we obtained 81 distinct papers. The screening phase aimed at eliminating non-relevant papers based on objective criteria: book chapters without available full text  (5) , as well as keynote (1) and workshop proposal (6) papers, were discarded, in order to keep only articles with enough content. Moreover, papers containing "tangible interaction" or "tangible user interfaces" keywords only in citations () or as related work () were also discarded. Finally, to select only papers dealing with relevant content, the keywords "physical" or "tangible" and "connect", "network", "communication" or "relationship" were searched in the full text and analyzed in their context in order to discard all papers that were not dealing with physical objects and connected objects.