dataesr/scientific-paragraphs-categorization huggingface dataset:
Control of the false discovery rate (FDR) Once p-values are computed, there is a problem of decision-making related to the choice of a threshold for p-values. We recommend to use the FDR approach where the objective is to provide a list of candidate genes with an expected proportion of false discoveries smaller than a specified value. For controlling the FDR, we consider the qvalue procedure as implemented in the qvalue R package that is less conservative than Bonferroni or Benjamini-Hochberg correction  (Storey and Tibshirani, 2003). The qvalue R package transforms the p-values into q-values and the user can control a specified value ↵ of FDR by considering as candidates the SNPs with q-values smaller than ↵.
Simulated data We simulated SNPs under an island model, under a divergence model and we downloaded simulations of range expansion  (Lotterhos and Whitlock, 2015). All data we simulated were composed of 3 populations, each of them containing 50 sampled diploid individuals (Table  2 ). SNPs were simulated assuming no linkage disequilibrium. SNPs with minor allele frequencies lower than 5% were discarded from the datasets. The mean F ST for each simulation was comprised between 5% and 10%. Using the simulations based on a island and a divergence model, we also created datasets composed of admixed individuals. We assumed that an instantaneous admixture event occurs at the present time so that all sampled individuals are the results of this admixture event. Admixed individuals were 7 generated by drawing randomly admixture proportions using a Dirichlet distribution of parameter (↵, ↵, ↵) (↵ ranging from 0.
Divergence model To perform simulations under a divergence model, we used the package simuPOP, which is an individual-based population genetic simulation environment  (Peng and Kimmel, 2005). We assumed that an ancestral panmictic population evolved during 20 generations before splitting into two subpopulations. The second subpopulation then split into subpopulations 2 and 3 at time T > 20. All 3 subpopulations continued to evolve until 200 generations have been reached, without migration between them (Figure  SI1 ). A total of 50 diploid individuals were sampled in each population. Selection only occured in the branch associated with population 2 and selection was simulated by assuming an additive model (fitness is equal to 1 2s, 1 s, 1 depending on the genotypes). We simulated a total of 3, 000 SNPs comprising of 100 adaptive ones for which the selection coefficient is of s = 0.
Range expansion We downloaded in the Dryad Digital Repository six simulations of range expansion with two glacial refugia  (Lotterhos and Whitlock, 2015). Adaptation occurred during the recolonization phase of the species range from the two refugia. We considered six different 8 simulated data with 30 populations and a number of sampled individual per location that varies from 20 to 60. Parameter settings for the different software When using hapflk, we set K = 1 that corresponds to the computation of the F LK statistic. When using BayeScan and OutFLANK, we used the default parameter values. For sNMF, we used K = 3 for the island and divergence model and K = 5 for range expansion as indicated by the cross-entropy criterion. The regularization parameter of sNMF was set to ↵ = 1000. For sNMF and hapflk, we used the genomic inflation factor to recalibrate p-values.
Control of the false discovery rate We evaluate to what extent using the packages pcadapt and qvalue control a FDR set at 10% (Figure  3 ). All SNPs with a q-value smaller than 10% were considered as candidate SNPs. For the island model, we find that the proportion of false discoveries is 8% and it increases to 10% when including admixture. For the divergence model, the proportion of false discoveries is 11% and it increases to 22% when including admixture. The largest proportion of false discoveries is obtained under range expansion and is equal to 25%. We then evaluate the proportion of false discoveries obtained with BayeScan, hapflk, OutFLANK, and sNMF (Figure  3 ). We find that hapflk is the most conservative approach (FDR = 6%) followed by OutFLANK and pcadapt (FDR = 11%). The software sNMF is more liberal (FDR = 19%) and BayeScan generates the largest proportion of false discoveries (FDR = 41%).
Statistical power To provide a fair comparison between methods and software, we compare statistical power for equal values of the observed proportion of false discoveries. Then we compute statistical power averaged over observed proportion of false discoveries ranging from 0% to 50%. We first compare statistical power obtained with the different statistical methods that have been implemented in pcadapt (Table  1 ). For the island model, Bayes factor, communality statistic and Mahalanobis distance have similar power (Figure  4 ). For the divergence model, the power obtained with Mahalanobis distance is 20% whereas the power obtained with the communality statistic and with the Bayes factor is respectively 4% and 2% (Figure  4 ). Similarly, for range expansion, the power obtained with Mahalanobis distance 10 is 46% whereas the power obtained with the communality statistic and with the Bayes factor is 34% and 13%.
Then, we compare statistical power in a divergence model where adaptation took place in one of the external branches of the population divergence tree. The software pcadapt and hapflk, which account for hierarchical population structure, as well as BayeScan are the most powerful in that setting (Figure  5  and Figure  SI5 ). The values of power in decreasing order are of 23% for BayeScan, of 20% for pcadapt, of 17% for hapflk, of 7% for sNMF and of 1% for OutFLANK. When including admixed individuals, the power of hapflk and of pcadapt hardly decreases whereas the power of BayeScan decreases to 6% (Figure  5 ). The last model we consider is the model of range expansion. The package pcadapt is the most powerful approach in this setting (Figure  6  and SI6). Other software also discover many true positive loci with the exception of BayeScan that provides no true discovery when the observed FDR is smaller than 50% (Figure  6  and SI6 ).
Running time of the different software Last, we compare the software running times. The characteristics of the computer we used to perform comparisons are the following : OSX El Capitan 10. 11. 3, 2,5 GHz Intel Core i5, 8 Go 1600 MHz DDR3. We discard BayeScan as it is too time consuming compared to other software. For instance, running BayeScan on a genotype matrix containing 150 individuals and 3, 000 SNPs takes 9 hours whereas it takes less than one second with 11 pcadapt. The different software were run on genotype matrices containing 300 individuals and from 500 to 50, 000 SNPs. OutFLANK is the software for which the runtime increases the most rapidly with the number of markers. OutFLANK takes around 25 minutes to analyse 50, 000 SNPs (Figure  SI7 ). For the other 3 software (hapflk, pcadapt, sNMF), analyzing 50, 000 SNPs takes less than 3 minutes.
Discussion The R package pcadapt implements a fast method to perform genome scans with next Simulations show that the R package pcadapt compares favorably to other software of genome scans. When data were simulated under an island model, population structure is not hierarchical because genetic differentiation is the same for all pairs of populations. Statistical power and control of the FDR were similar for all software. In presence of hierarchical population structure (divergence model) where genetic differentiation varies between pairs of populations, the ranking of the SNPs is software dependent. The software pcadapt and hapflk provide the most powerful scans whether or not simulations include admixed individuals. OutFLANK implements a F ST statistic and because adaptation does not correspond to the most differentiated populations, it fails to capture adaptive SNPs (Figure  5 )  (Bonhomme et al.
, 2010; Duforet-Frebourg et al. , 2016). BayeScan does not assume equal differentiation between all pairs of populations, which may explain why it has a good statistical power for the divergence model. However its statistical power is severely impacted by the presence of admixed individuals because its power decreases from 24% to 6% (Figure  5 ). Understanding why BayeScan is severely impacted by admixture is out of the scope of this paper. In the range expansion model, BayeScan returns many null q-values (between 376 and 809 SNPs out of 9, 899 neutral and 100 adaptive SNPs) such that the observed FDR is always larger than 50%. Overall, we find that pcadapt and hapflk provides comparable statistical power. Compared to other software, they provide optimal or near optimal ranking of the SNPs in different scenarios including hierarchical population structure and admixed individuals.
The main difference between the two software concerns the control of the FDR because hapflk is found to be more conservative. Because NGS data become more and more massive, careful numerical implementation is crucial. There are different options to implement PCA and pcadapt uses a numerical routine based on the computation of the covariance matrix ⌦. The algorithmic complexity to compute the covariance matrix is proportional to pn 2 where p is the number of markers and n is the number of individuals. The computation of the first K eigenvectors of the covariance matrix ⌦ has a complexity proportional to n 3. This second step is usually more rapid than the computation of the covariance because the number of markers is usually large compared to the number of individuals. In brief, computing the covariance matrix ⌦ is by far the most costly operation when computing principal components.
generation sequencing data. It can handle datasets where population structure is continuous or datasets containing admixed individuals. It can handle missing data as well as pooled sequencing data. The 2. 0 and later versions of the R package implements a robust Mahalanobis distance as a test statistic. When hierarchical population structure occurs, Mahalanobis distance provides more powerful genome scans compared to the communality statistic that was implemented in the first version of the package (Duforet-Frebourg et al. , 2016). In the divergence model, adaptation occurs along an external branch of the divergence tree that corresponds to the second principal component. When outlier SNPs are not related to the first principal component, the Mahalanobis distance provides a better ranking of the SNPs compared to the communality statistic.
Data Accessibility Island and divergence model data : doi :10. 5061/dryad. 8290n Range expansion simulated data : doi :10. 5061/dryad. mh67v. Files : 2R_R30_1351142954_453_2_NumPops=30_NumInd=20 2R_R30_1351142954_453_2_NumPops=30_NumInd=60 2R_R30_1351142970_988_6_NumPops=30_NumInd=20 2R_R30_1351142970_988_6_NumPops=30_NumInd=60 2R_R30_1351142986_950_10_NumPops=30_NumInd=20 2R_R30_1351142986_950_10_NumPops=30_NumInd=60.
(2005) , focusing primarily on ways to achieve wide-angle interplanetary imaging and efficient on-board data processing (given the limited telemetry available from L5). Larger L5 mission concepts have been proposed more recently, with in particular the Earth-Affecting Solar Causes Observatory (EASCO;  Gopalswamy et al. , 2011a; 2011b). This mission concept proposes to fill the gaps in observational capabilities of past missions (e. g. , SOHO and STEREO), with key additional measurements such as radio, magnetograph and X-ray imaging. EASCO was studied in detail by NASA, including the full mission profile that differs greatly from that of INSTANT owing to EASCO's much broader payload. Strugarek et al. (2015)  also recently proposed a large mission concept for both space weather science and operational purposes, with two spacecraft separated by 34° east and west from the Earth on its orbit for stereoscopic imaging of Earth-bound disturbances.
, the presence of cavities, the extent of the compression region, and the location of current sheets and likely null points (e. g. , reviews of CME properties by  Chen (2011)  and  Webb and Howard (2012) ). By providing coronal magnetic field and density measurements, the INSTANT concept provides a direct assessment of current CME initiation models. The cruise period towards L5, with higher telemetry, is well suited to accomplish this task, and the experience in calibration and data processing enables optimization studies for observations farther at L5. When at L5, INSTANT will provide the opportunity to compare Earth-bound CME initiation and magnetic structure observations with associated in-situ measurements near Earth and elsewhere in the heliosphere.
2. 3). As shown by STEREO (e. g. ,  Savani et al. , 2009 Savani et al. , , 2010)) , such observations should have a sufficient spatial and temporal resolution for appropriate study of CME dynamics, with the highest resolutions close to the Sun (MR7). Fully disentangling projection effects to study the 3D properties of CMEs from a single viewpoint requires measurements beyond total brightness, namely polarization information. This capability was demonstrated with SOHO/LASCO C2 and STEREO/COR2 polarization data covering distances up to 15 RS  (Moran & Davila, 2004; de Koning & Pizzo, 2011). INSTANT will pursue this path to the next step by expanding the distances at which polarization measurements are made, up to 200 RS and beyond, thus being the first mission to make polarization measurements in wideangle FOV heliospheric imaging (MR8).
g. ,  Möstl et al. , 2009; Liu et al. , 2010b; 2011; 2013; Rouillard et al. , 2011; Webb et al. , 2012). The study of CMEs directed in between Earth and L5 would strongly benefit from in-situ ion and magnetic field data at the observing spacecraft (MR11). INSTANT offers the possibility of confirming the presence of CME substructures (shock, sheath, flux rope) by connecting coronal and heliospheric imaging with in-situ observations at 1 AU. Comparison of CME properties with in-situ data at both L1 and INSTANT is possible at all times in the proposed scenario.
Performance and telemetry resources The expected count rates and efficiencies of MAGIC were studied using measurements of components similar to those that will be used on MAGIC. The intensities were computed using a semi-empirical model of the corona. They are consistent with Lyman-α UVCS (UltraViolet Coronagraphic Spectrometer) observations on board SOHO. The range of exposure times corresponds to a signal-to-noise ratio SNR=30 at 1. 3 RS and SNR=5 at 3 RS for a typical low coronal magnetic field strength; these are much improved for stronger fields in active regions and CMEs (Section 4. 2). For magnetography, the SNR can be increased 4 times or more by binning the data (2×2, 3×3, etc. ). MAGIC is by far the most telemetry-demanding instrument of the INSTANT concept. Specific attention has thus been given to data products and ensuing telemetry requirements as a function of science phase.
Because PROBA is a microsatellite platform and, thus, has a limited volume, the propulsion subsystem needed for insertion at L5 must be sized accordingly. Based on the combined delta-V needs and limited volume available, an electric-based ion engine propulsion system was studied and designed based on previous flown systems (SMART-1). The INSTANT spacecraft needs to cope with long distance (up to 1 AU) communication and operations. The telemetry, tracking and command (TT&C) subsystem must ensure a stable link, both during cruise and at L5, with the ground segment to support the instrument data downlink. To limit the burden on board the spacecraft (power and antenna diameter), the mission profile requires a ground station which hosts a large diameter antenna (of order 50 m) for downlink and uplink in X-band.
This is easily handled in the studied INSTANT design since all science data are recorded on the spacecraft-integrated mass memory, where up to 88 Gbits are available, corresponding to > 10 days of nominal science operations at L5 at the rate of ~60 kbps. Selection of the high-resolution data to be downlink, i. e. , during CME eruptions, can be planned from ground using beacon data, and knowledge from other spacecraft and ground measurements. On-board triggers may also be implemented. Finally, smaller antennas may be used for downlinking beacon data products in real time if space weather operational activities are planned.
Acknowledgments. The authors acknowledge the inputs and support from more than 180 collaborators to the INSTANT mission proposal submitted to the  ESA  and CAS call for small missions in 2015. Although INSTANT was not selected in that call, the concept will be proposed in future opportunities at  ESA  or other agencies. Work at IRAP was supported by  CNES  and  CNRS. BL wishes to thank  D. Lario  for providing the Figure from which Figure 5 is adapted.
Introduction: Individuals with Parkinson's disease (PD) have to deal with several aspects of voice and speech decline and thus alteration of communication ability during the course of the disease. Among these communication impairments, 3 major challenges include: (1) dysarthria, consisting of orofacial motor dysfunction and dysprosody, which is linked to the neurodegenerative processes; (2) effects of the pharmacological treatment, which vary according to the disease stage; and (3) particular speech modifications that may be language-specific, that is, dependent on the language spoken by the patients. The main objective of the FraLusoPark project is to provide a thorough evaluation of changes in PD speech as a result of pharmacological treatment and disease duration in 2 different languages (French vs European Portuguese).
Methods and analysis: Individuals with PD are enrolled in the study in France (N=60) and Portugal (N=60). Their global motor disability and orofacial motor functions is assessed with specific clinical rating scales, without (OFF) and with (ON) pharmacological treatment. 2 groups of 60 healthy age-matched volunteers provide the reference for between-group comparisons. Along with the clinical examinations, several speech tasks are recorded to obtain acoustic and perceptual measures. Patient-reported outcome measures are used to assess the psychosocial impact of dysarthria on quality of life. approved by the local responsible committees on human experimentation and is conducted in accordance with the ethical standards. A valuable largescale database of speech recordings and metadata from patients with PD in France and Portugal will be constructed.
The main objective of the FraLusoPark project is to provide an extensive evaluation of dysarthric speech in PD as a result of pharmacological treatment and disease duration, using acoustic parameters (voice and prosody), perceptual markers (intelligibility) and patient-reported outcome measures (PROMs; psychosocial impact on quality of life) in speakers of two different languages (French and European Portuguese). Based on a large-scale binational collaboration, the interdisciplinary FraLusoPark project aims to address these issues by providing important insights in the domains of neurodegenerative disorders, speech sciences, neuropsychology, clinical research and patient rehabilitation.
Statistical analyses The analyses of the data (acoustic, clinical measures and PROMs) will be performed with linear mixed-effects models that account for the variability across individuals, using the latest version of the statistical software R (R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria: 2014. ISBN 3--900051-07-0, http://www. R-project. org/). For each performance measure, the between-group factors group ( patients vs controls), disease duration (early vs medium vs advanced) and language (French vs European Portuguese) will be investigated. In addition, we will explore the effects of the within-patient factor medication (OFF vs ON) for all measures. Further relevant participant-related measures such as age, gender and education level will also be taken into account in the analyses.
ETHICS AND DISSEMINATION This study has been approved by the local responsible committees on human experimentation (France: Comité de Protection des Personnes, Sud Méditerranée 1, project reference number 13-84, approval date 9 January 2014; Portugal: Ethics Committee of the Lisbon Academic Medical Centre, project reference number 239-14, approval date 1 June 2014). The study is conducted in accordance with the ethical standards of the Declaration of Helsinki. 86 The patients are included in the study after providing their written informed consent. The FraLusoPark trial is registered under the reference NCT02753192 (26 April 2016) on https://clinicaltrials. gov/. Results of the FraLusoPark project will be disseminated at several research conferences at the national and international levels and published as articles in peer-reviewed journals and clinical magazines.
The publication strategy is based on one principal article reporting the main results of the project and several subsequent articles deriving from it, including more detailed analyses of specific subdimensions of the speech and voice deficits. Owing to inter-speaker variability, any generalisation drawn from speech parameters in the clinical population requires data from a large number of speakers. 87 The FraLusoPark project is in line with this idea in that it builds a large-scale corpus of PD speech recordings and includes a large set of metadata (clinical examinations, speech measurements, linguistic features, patient-based indices). This allows a more accurate description of PD dysarthria, documenting the evolution of the symptoms and their response to pharmacological treatment. Both in medical (eg, http://www.
mrc. ac. uk/research/research-policy-ethics/ data-sharing/data-sharing-population-and-patient-studies/) and linguistic (http://sldr. org/) domains, data sharing is important to maximise the lifetime value of human health data. It is our intention to contribute to this practice by archiving our data for long-term preservation and making them accessible after the completion of our analyses. Furthermore, an important recommendation from the International Classification of Functioning, Disability and Health 88 is to improve quality of healthcare and to encourage clinicians to adopt a more holistic approach to the assessment and treatment of patients. Research in the field of speech sciences needs to incorporate this vantage point when studying pathological speech. The FraLusoPark project is in line with this perspective and will provide important recommendations for speech and voice assessments in patients with PD.
Funding This study is supported by a bilateral transnational funding between France and Portugal: support from the  French government , through the  French National Agency for Research (ANR-Agence Nationale de la Recherche -grant number  ANR-13-ISH2-0001-01 ) and from the  Portuguese government , through the  Portuguese National Foundation for Science and Technology (FCT-Fundação para a Ciência e a Tecnologia -grant number  FCT-ANR/NEU-SCC/0005/2013 ). CA-C wishes to thank his PhD grant scheme co-funders:  PACA Regional Council and Orthomalin  (http://www. orthomalin. com/).
Read-based phasing allows to reconstruct the haplotype structure of a sample purely from sequencing reads. While phasing is a required step for answering questions about population genetics, compound heterozygosity, and to aid in clinical decision making, there has been a lack of an accurate, usable and standards-based software. WhatsHap is a production-ready tool for highly accurate read-based phasing. It was designed from the beginning to leverage third-generation sequencing technologies, whose long reads can span many variants and are therefore ideal for phasing. WhatsHap works also well with second-generation data, is easy to use and will phase not only SNVs, but also indels and other variants. It is unique in its ability to combine read-based with genetic phasing, allowing to further improve accuracy if multiple related samples are provided.