dataesr/scientific-paragraphs-categorization huggingface dataset:
DISCUSSION WES offers unprecedent opportunities for identifying HMZ deletions as novel causal determinants of human diseases, but it poses a number of computational challenges. Most current methods for detecting HMZ deletions compare the depth of coverage between a given exome and the rest of the exomes in the dataset. However, coverage depth is heavily dependent on sequencing conditions, which are continually evolving in typical laboratory settings. Thus, the exome data generated over time are inevitably heterogeneous, complicating the discovery of deletions. Using HMZDelFinder_opt with both validated disease-causing deletions and simulated data, we demonstrated that the a priori selection of a reference control set with a coverage profile similar to that of the WES sample studied reduced the number of deletions detected, while improving the ranking of the true HMZ deletion.
ACKNOWLEDGEMENT We thank the members of the  Human Genetics of Infectious Diseases Laboratory  for helpful discussions. We also thank  Yelena Nemiroskaya ,  Dominick Papandrea ,  Mark Woollett ,  Dana Liu  ( St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA ), and  Cécile Patissier ,  Lazaro Lorenzo-Diaz ,  Christine Rivalain  ( Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France ) for their assistance.
FUNDING This research was supported in part by the  National Institutes of Health (NIH)  (grants  R01AI088364 ,  R37AI095983 ,  U19AI111143 ,  R01AI127564 ,  P01AI061093  to J. -L. C. ), the  National Center for Research Resources  and the  National Center for Advancing Sciences of the NIH  (grant  8UL1TR001866 ), the  Yale Center for Mendelian Genomics  and the  GSP Coordinating Center  funded by the  National Human Genome Research Institute (NHGRI)  ( UM1HG006504  and  U24HG008956 ), the  Rockefeller University , the  St. Giles Foundation ,  Howard Hughes Medical Institute ,  Institut National de la Santé et de la Recherche Médicale (INSERM) ,  University of Paris , the  Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence  ( ANR-10-LABX-62-IBEID ), the  French Foundation for Medical Research (FRM)  ( EQU201903007798 ), the  SCOR Corporate Foundation for Science , and the  French National Research Agency (ANR)  under the " Investments for the future " (grand number  ANR-10-IAHU-01 ),  GENMSMD  ( ANR-16-CE17.
0005-01 , to JB),  ANR-LTh-MSMD-CMCD  ( ANR-18-CE93-0008-01  to A. P),  Fonds de Recherche en Santé Respiratoire  ( SRC2017  to J. B. ),  ProgLegio  project ( ANR-15-CE17-0014 ). and  ECOS Nord  ( C19S01-63407  to J. B. ).
Context. The Solar Orbiter mission, with an orbit outside the Sun-Earth line and leaving the ecliptic plane, opens up opportunities for the combined analysis of measurements obtained by solar imagers and spectrometers. For the first time, different space spectrometers will be located at wide angles to each other, allowing three-dimensional (3D) spectroscopy of the solar atmosphere. Aims. The aim of this work is to prepare the methodology to facilitate the reconstruction of 3D vector velocities from two stereoscopic LOS Doppler velocity measurements using the Spectral Imaging of the Coronal Environment (SPICE) on board the Solar Orbiter and the near-Earth spectrometers, while widely separated in space. Methods. We develop the methodology using the libraries designed earlier for the STEREO mission but applied to spectroscopic data from the Hinode mission and the Solar Dynamics Observatory.
Introduction The Solar Orbiter (SO) space mission  (Müller 2020) , launched in February 2020, provides both remote sensing and in situ measurements of the solar atmosphere and heliosphere. The main goal of this mission is to understand how the heliosphere is formed and sustained. The trajectory of Solar Orbiter takes it out of the Earth's orbit and into an orbit around the Sun, reaching within the orbit of Mercury to 0. 28 AU. A spacecraft whose orbit is away from the Sun-Earth line opens up huge possibilities for the representation of the three-dimensional (3D) imaging and spectroscopic data together with near-Earth imaging and spectroscopy. For the first time, spectrometers will be located at different angles from each other, allowing 3D spectroscopy of the solar atmosphere. The presence of persistent high-temperature, high-speed upflows from the edges of active regions  (Harra et al.
We do this using the STEREO triangulation technique of EUV images of active regions and we develop novel methods of analytical geometry in space to determine 3D velocities in coronal loops. An advantage of having two different views of an active region is that one can determine the projection angles of the loops, and hence direction of plasma flows along them. We use Hinode/EIS data acquired at different times in order to replicate the situation of two spacecraft with spectrometers on board, and we choose an active region that did not show significant changes in time (Section 2). In addition, we describe methods with which to reconstruct the velocity vectors; these will be released as a suite of 3D spectroscopy algorithms (Software package DOVES --DOppler VElocities Stereoscopically) for velocity vector reconstruction.
Instrumentation Initial data for 3D velocity reconstruction includes a stereoscopic pair of EUV images, and simultaneous Doppler shifts measurements from two angularly separated spectrometers. Now, to simulate the stereo view we get usable simultaneous data sets with SPICE, we use solar rotation to produce two different viewpoints, as it was done for STEREO sofware preparation. These viewpoints are imitated now by imaging data obtained by the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamic Observatory (SDO,  Pesnell et al. 2012 ) and spectroscopic data from Hinode/EIS. By applying direct triangulation methods to SDO/AIA intensity images, we restore the 3D coordinates of the observed structures. Then, the triangulation of the Doppler shifts observed by Hinode/EIS allows us to restore the vector velocities in these structures.
Hinode/EIS data We used the eis_prep. pro routine in SolarSoftware to calibrate the Hinode/EIS data. The dark current and cosmic rays were removed, and the hot pixels were corrected. The intensity DN (digital number) values were calibrated to the spectral radiance in units of erg • (cm 2 • s • sr • Å) -1. We focused on the strongest emission line observed by Hinode EIS, Fe xii at 195. 12 Å with formation temperatures log T = 6. 1. For each spectrum, we fitted a single Gaussian function with the eis_auto_fit routine and obtained the line peak intensity, Doppler velocity, and line width using eis_get_fitdata. pro.
Hinode/EIS and SDO/AIA data co-alignment Dynamic structures on the solar surface evolve with a significantly shorter time than the duration of the Hinode/EIS raster observation of 67 min. We created a pseudo SDO/AIA raster analogous to the Hinode/EIS raster to compensate for possible dynamic changes. To this end, we extracted the SDO/AIA data closest in time to each position of the Hinode/EIS slit. These data were merged into a single SDO/AIA map (hereafter referred to as "artificial SDO/AIA raster map"), corresponding to Hinode/EIS raster map using the cross-correlation method described herein. The offset between the artificial SDO/AIA raster map and the Hinode/EIS raster map was applied together with a pointing correction. Based on the new Hinode/EIS pointing details, the new artificial SDO/AIA raster map was created and aligned to the new Hinode/EIS map.
3D-triangulation software In this study, we use the HEEQ system. The origin of the HEEQ system is the intersection of the solar equator with the central meridian as seen from Earth, and the solar feature location is given either in Cartesian coordinates X, Y, Z (HEEQ coordinates) or in spherical coordinates (Stonyhurst heliographic coordinates: latitude Θ, longitude ϕ and heliospheric radius R)  (Thompson 2006 ) (see Figure  3 ). The locations of the features were processed with the World Coordinate System routine scc_measure. pro of the Solar Software  (Thompson 2006 ). The structures were traced in stereoscopic pairs of images using projections along the epipolar lines. The routine uses a combination of the information in the header, such as the pixel-todegree conversion, and the SPICE (Spacecraft Planet Instrument C-matrix Events orientation) database of orbital kernels by calling the routine convert_sunspice_coord.
Discussion and conclusions We have developed a technique that reconstructs velocity vectors in coronal loops from the Doppler maps and EUV images obtained by two spacecraft located at significant (on a heliospheric scale) distances from each other. The methodology is built upon the dynamic solar rotation EUV spectroscopy and on STEREO triangulation methods for coronal loops observed in optically thin coronal EUV emissions lines  (Aschwanden 2011). Novel algorithms use methods of spatial analytical geometry in order to determine 3D velocities in coronal loops using different LOSs Doppler shifts measurements. The study is inspired by the launch of the Solar Orbiter in February 2020, the first solar mission to travel far beyond the ecliptic plane, which carries the EUV spectrometer. For the first time, stereoscopic pairs of solar Doppler maps will be available by combining data from the distant Solar Orbiter and the near-Earth spectrometers.
The first attempt of Doppler maps stereoscopic observations in coronal lines was conducted by the consortium during Solar Orbiter cruise phase on 21-28 April 2021, as part of a quadrature observation campaign. Test data for vector velocity reconstruction will be available for the community shortly after calibration. Velocity vectors in plasma flows propagating at small angles to the observation plane (the epipolar plane, where the LOS Doppler velocities are located) can be reconstructed with higher accuracy, but the triangulation error may increase. The high spectral and spatial resolution of the instruments also contributes to an increase in the accuracy of the 3D velocity reconstruction, i. e. , Solar Orbiter observations in perihelion positions minimise triangulation errors. The applicability of the methodology is determined by the correct solution of two problems, stereoscopic tie-pointing and triangulation of features, and application of analytical geometry in space.
Acknowledgements. The authors acknowledge the anonymous referee and the Editor for providing valuable suggestions and comments. We are grateful to the  EUI , SPICE instrument teams and to ESA Solar Orbiter Remote Sensing working group for detailed discussions during the consortium meetings, to  Hardi Peter  and  Bart de Pontieu  for discussions about the wavelengths and stereoscopic observations of Doppler maps. OP is grateful to  Conrad Schwanitz  for sharing his data analysis experience,  William Thompson  for the vector velocity definition velocity and to  Anik de Groof  for Solar Orbiter orbits and observations planning. OP acknowledges funding from  Karbacher Fonds. KB acknowledges funding from  SNSF. CM acknowledges grants  PICT 2016-0221  ( ANPCyT ) and  UBACyT   20020170100611BA. CM is a member of the  Carrera del Investigador Científico of the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET).
From an input containing multiple sequences, the server will first explore whether any homologous complex is available as a template to predict the structure of an assembly by comparative modeling techniques (Figure  1 ). Only a subset of the query proteins may fulfill these conditions and InterEvDock3 will build template-based models for the largest such subset. For interfaces that cannot be modeled by homology, InterEvDock3 proposes two complementary free docking approaches. The first one is particularly well adapted when large coMSAs can be generated for the subunits of interest. It exploits the covariation-inferred contact maps that can be generated from servers and methods that implement Direct Coupling Analyses such as EvComplex  (33)  or that combine this analysis with deep learning techniques such as ComplexContact  (34)  or trRosetta  (35).
The third modeling solution proposed by InterEvDock3 is a new strategy we developed for atomic-based scoring integrating interface coevolution  (36). For each model sampled by FRODOCK  (16) , atomic models of interfaces of coevolved homologs are scored using a successful consensus strategy exploiting the complementarity of scores such as InterEvScore  (37) , SOAP-PP  (38)  and Rosetta interface score  (39). Moving from a coarse-grained integration of evolutionary information to an atomic representation, the success rates of InterEvDock3 were increased by more than 20%. In addition to these three novelties, the InterEvDock3 server inherits many features of previous versions that allowed our group to rank among the best predictors on past CAPRI challenges  (40) (41) (42). Such useful features include automatic generation of co-alignments for multi-subunit inputs, handling of user-specific distance constraints, interactive viewers for rapid visual inspection complemented with tailored PyMOL scripts to facilitate the comprehensive analysis of the docking results, and the possibility to use a previous job id session for hot restarts.
These functionalities have been adapted and extended to the new methodological improvements in order to facilitate their use. The InterEvDock3 pipeline was extensively tested and the free docking part was benchmarked on 230 unbound partners of the Weng database  (43)  and 812 unbound homology models from the PPI4DOCK database  (30). 40% and 35% of the 230 and 812 cases, respectively, have an acceptable or better solution among the top 10 consensus models returned by InterEvDock3. InterEvDock3 also outputs a list of the 10 residues most likely involved in the interface and at least one residue was correctly predicted in 91% of the 812 benchmark cases. We also present several challenging cases to illustrate the extended applicability reached by the incorporation of novel evolution-based docking strategies.
Templatebased modeling (mode 1) is in general more reliable than free docking approaches and should be favored if possible. In case large multiple sequence alignments can be obtained, it is advised to run first the coevolution-derived contact mode (mode 2) which can strongly restrict the relative orientations between docked partners. Mode 3 should be privileged in cases where only shallow co-MSAs can be obtained. using a protocol we recently developed to identify, among a list of interacting proteins, those which have homologs structurally characterized in complex with each other  (44). The latter protocol was also included in the Proteo3Dnet server  (45). Close and remote homologous complexes are identified using HHsearch  (46)  and the computed alignments are used to create a structural assembly by threading the maximum number of input subunits possible.
(B) Structural model obtained using InterEvDock3 in mode 2 (by applying the top 100 contacts predicted by the ComplexContact server) for the complex between E. coli MutS homodimer and MutL homodimeric N-terminal domain (PDB:1B63). In the crystal structure of the complex, a single domain of MutL was crystallized (5AKB). A PyMol script 'start analysis cmap. pml' is distributed in the downloadable results archive to get all the predicted contacts in the map which were satisfied in the model as shown in the figure. context of protein structures or structural models used as free docking inputs, InterEvDock3 uses a grouping strategy in which vicinal sequence positions are considered equivalent. By default, a central position is grouped with its two upstream and two downstream positions (this number can be adjusted in the advanced options and redundant grouping can be canceled by setting the parameter to 0).
Free docking using a consensus scoring approach running at the atomic level To identify the most likely coevolved interfaces, free docking poses can be rescored using a consensus approach combining up to five different scores (Figure  1. 3). The scoring protocol exploits coMSAs of both input partners, automatically and efficiently built if not provided by the user, even for oligomeric inputs. The novelty in InterEvDock3  (36)  is that a subset of 10 to 40 representative couples of homologous sequences are selected from the coMSAs and are rapidly modeled at the atomic level to be scored simultaneously. The representative pairs of sequences form a group of so-called interolog sequences. For every docking pose and for each interolog, the server rapidly generates an atomic model of the interface with side-chain conformations predicted using OSCAR-star (47) without modeling insertions.
Server output The web page resulting from an InterEvDock3 submission contains information about the best ranked decoys, which can be explored interactively thanks to the NGL applet  (50). Models can be minimized or taken without modifications with respect to the input structures. Detailed results are available in a downloadable archive, also containing a script for easy loading and offline visualization of the best docking solutions with PyMOL (The PyMOL Molecular Graphics System, Schr ödinger, LLC). The InterEvDock3 server benefits from parallelized implementation in the dedicated infrastructure built at RPBS and from data privacy ensured in the Mobyle framework. Several tutorial cases using sequences as input to the docking or adding contact maps are available on the In-terEvDock3 submission page, presented in a video tutorial and described in the help page at https://bioserv.
02 and FRODOCK 2. 1. We tested 230 targets of the Weng dataset (unbound experimental monomers) together with 812 targets from the PPI4DOCK dataset (unbound homology models). As shown in Figure  3A  and Supplementary Figure  S5A , in all the scoring variants, a significant increase in the number of targets with Acceptable or better models among the top 10 decoys is observed reaching up to 35% and 39. 6% of correct predictions on the PPI4DOCK and Weng dataset, respectively. InterEvDock3 can take advantage of several atomic-based scores in addition to SOAP-PP such as the Rosetta interface score applied either at the level of the master sequence or applied as for SOAP-PP on all the interologs (so-called IED3-atom slow mode). This strategy was thoroughly benchmarked, showing improvements with respect to several standard scoring functions on the two benchmark datasets  (36).
In addition to the top 10 consensus models, users can also download an output archive containing the PDB files of the top 50 models of every individual score used in the consensus together with a Py-MOL script to visualize important features mapped at the surface of the models (Figure  3B ). Of key interest for experimental biologists using mode 3 presented in Figure  1 , InterEvDock3 predicts a list of 10 residues most likely involved in the complex interface that can be targeted for mutagenesis (5 on each partner). For these residue predictions, we reach 91% success rate, with 737 of the 812 PPI4DOCK benchmark cases having at least one of the 10 predicted residues involved in the actual interface (Supplementary Figure  S5B ).
ACKNOWLEDGEMENTS We are very grateful to  Andrej Sali  ( SOAP-PP ),  Tal Pupko  ( Rate4Site ),  Peter Rose  (NGL viewer),  Sjoerd de Vries (DaReUS-Loop ),  Kazutaka Katoh  (MAFFT),  Daron Standley  (OSCAR-star), Johannes S öding,  Milot Mirdita  and  Christian Roth  (HHsuite) and the  RosettaCommons community  for making their methods available for implementation in the InterEvDock3 server.
FUNDING French Infrastructure for Integrated Structural Biology (FRISBI)  [ ANR-10-INSB-05-01  to R. G. ];  Agence Nationale de la Recherche  through grants  CHIPSET  [ ANR-15-CE11-0008-01  to R. G. ];  ESPRINet  [ ANR-18-CE45-0005-01  to J. A. ];  French Institute for Bioinformatics (IFB)  [ ANR-14-2011-IFB  to G. P. ];  IdEx Université de Paris  [ ANR-18-IDEX-0001  to P. T. ],  IDEX Paris-Saclay  [ IDI 2017  to C. Q. ];  MINECO  [ BFU2016-76220-P  to P. C. ];  AEI/FEDER ,  UE  [ PID2019-109041GB-C21  to P. C. ]. Funding for open access charge:  FRISBI  [ ANR-18-CE45-0005-01 ].
It has even been said that they "should be regarded as methods of last resort"  (Sellwood 1997 ). Therefore we mainly adopt an efficient (hierarchical) method which makes it feasible to carry out simulations with larger particle numbers, and employs softening to further reduce collisionality; for these reasons our method of first resort in this work is gyrfalcON  (Dehnen 2002). This is used to generate the main bulk of the numerical results, which are in the earlier parts of Sec. 3. Elsewhere, however, in Sections 3. 4 and 4. 3, we do resort to use of the collisional code NBODY6  (Nitadori & Aarseth 2012). The matrix method dates back to the work of Kalnajs 1977 (though his emphasis was on disks) and to the study of non-rotating spherical systems by  Polyachenko & Shukhman (1981). For such systems the formulation we employ  (Rozier, et al.
(d) High-inclination models Lastly we have a set of models in which the Lynden-Bell demon works only on stars of high inclination  >  4 /2. Such models may give additional indications of the geometrical and kinematic characteristics of orbits which contribute strongly to instability. These are the only initial models considered in this paper, but many variants are possible. For example, in the high-shear models, the axis of rotation of the least bound stars may be chosen differently from that of the most bound stars. Many such models can be explored by setting up initial conditions with the software PlummerPlus 1.
Growth rate for the maximally rotating model at each  1 , for several values of. We have avoided the isotropic case  = 0, as it is known  (Rozier, et al. 2019 ) that any instabilities here could belong to a different family from those at smaller (more negative) values of. The result of two independent simulations is given for  1 = 1. values of v  (0. 5). Incidentally, this value was conveniently available, but values at other neighbouring radii might well be equally useful, as illustrated just below. The maximum growth rate occurs when  = 1, i. e. the Lynden-Bell demon acts at its maximum level. But now the entire dataset (all values of  ≤ 0,  and  1 ; see Fig. 8 ) can be grasped in outline by means of the foregoing analysis. The axes correspond to the Ostriker-Peebles stability parameter and the azimuthal streaming speed at the virial radius, and the size of the symbol encodes the growth rate of the bar.
Conclusions This paper focuses on the collisionless stability of rotating, spherical stellar systems, using a mix of -body simulations, the matrix method for the evolution of perturbations, and some physical ideas. Our starting point is a set of anisotropic Plummer models  (Dejonghe 1987) , whose anisotropy is parametrised by a parameter ; our focus is on models with  < 0, whose velocity distribution is tangentially biased. To these models we apply different versions of the Lynden-Bell demon  (Lynden-Bell 1960) , in which the rotation of a fraction  of stars is reversed in a region of phase space defined in terms of integrals of motion, and parametrised in various ways by a parameter. Instances of these models were generated with the publicly available software PlummerPlus, and their evolution studied using the public version of gyrfalcON 9.