dataesr/scientific-paragraphs-categorization huggingface dataset:
Links to biocurated data of IG and TR genes and alleles from fish to humans are provided in IMGT ® Creations and updates (http://www. imgt. org/IMGTinformation/c reations/) (access in 'References and News' on the IMGT ® Home page) (accessed on 22 February 2022), online since October 1998. IG and TR nomenclature (genes and alleles names) and IMGT unique numbering of the IMGT ® Creations and updates are validated by the International Union of Immunological Societies (IUIS) Nomenclature Committee (NOM) Immunoglobulins (IG), T cell receptors (TR) and major histocompatibility (MH) Sub-Committee (IMGT-NC)  [114]. A primary axis of research and development in immunogenetics and immunoinformatics consists in deciphering the genomic organization of the IG and TR loci in jawed vertebrates. Indeed, new IMGT genes and alleles, described with the IMGT nomenclature, IMGT unique numbering and IMGT standardized keywords and labels  [1] , enrich the IMGT ® databases, tool reference directories and web resources for a better knowledge of natural IG and TR repertoires.
Advent of Immunoinformatics The V, D, J, and C genes which code the antigen receptors were officially recognized as 'genes', as were the conventional genes, at the 10th Human Genome Mapping (HGM10) Workshop, in New Haven in 1989, marking the creation of IMGT ® and the advent of immunoinformatics  [1]. The Homo sapiens TRG locus  [115]  was the first complete antigen receptor locus officially approved in 1989 for entry in the HGM database  [116, 117]. In 1992, the Homo sapiens IMGT genes and alleles names were endorsed by the WHO-IUIS NOM (https://iuis. org/committees/nom/) (accessed on 22 February 2022). IMGT-NC became the first IUIS Nomenclature Sub-Committee for immunoglobulins and T cell receptors  [114]  in charge of providing the IG and TR genes and alleles names and promoting IMGT standards  [118] [119] [120] [121].
Entries of the FactsBooks  [2, 3]  provide information on assignment to subgroups and nomenclature, gene definition and functionality, gene location, allelic polymorphism, standardized sequence alignment with protein translation, framework and complementarity determining region (CDR-IMGT) lengths, two-dimensional representations (or Colliers de Perles), IMGT/LIGM-DB and EMBL/GenBank accession numbers, genome database accession numbers (GDB, LocusLink) and key references  [2, 3]. This information has served as templates for the IMGT Repertoire (IG and TR) sections on the IMGT website, in the IMGT Web resources (the 'IMGT Marie-Paule page') (IMGT ® http://www. imgt. org (accessed on 22 February 2022), IMGT Repertoire (IG and TR) (1). Locus and genes; (2). Proteins and alleles; (3). 2D and 3D structures; (4).
Probes and RFLP;  (5). Taxonomy;  (6). Gene regulation and expression;  (7). Genes and clinical entities). Basic IMGT Web resources include Gene tables, Alignment of alleles, Protein displays, Colliers de Perles, Locus representations, Potential germline repertoire with CDR-IMGT lengths, Locus gene order, copy number variations (CNV) and haplotypes)  [5]. This detailed identification, description and classification of the human IG and TR loci, genes and alleles  [2, 3] , using the IMGT Scientific chart rules, is the result of a huge work of annotation and expert analysis, by LIGM, of tens of thousands of nucleotide sequences from phages, cosmids or contigs submitted by the authors to the generalist nucleotide databases (EMBL database, now European Nucleotide Archive (ENA)  [123] , GenBank  [124]  and DNA Databank of Japan (DDBJ)  [125].
The annotated sequences were integrated into the newly created IMGT/LIGM-DB  [10, 11] , using the EMBL/GenBank/DDBJ accession numbers in order to facilitate interoperability with the generalist nucleotide databases. The Nature and Science papers on the human genome sequencing  [126, 127] , published in 2001, contain limited information on the genes of the adaptive immune responses. However a careful analysis of the maps published in these papers allowed us to confirm the chromosomal localizations of the seven main loci: IGH, IGK and IGH (for the immunoglobulins), TRA, TRB, TRG and TRD (for the T cell receptors), described in 2001, in the Immunoglobulin FactsBook  [2]  and T cell receptor FactsBook  [3] , respectively, and determined by an analysis of translocations involving the IG and/or TR loci in leukemia and lymphoma (http://www.
There are also direct links to IMGT/GENE-DB and generalist genomic databases entries in two formats, HTML tables and CSV format. On 25 November 2021, IMGT/GENE-DB data include 732 Homo sapiens IG and TR genes (with links to HGNC, NCBI Gene, Ensembl, GenAtlas, GeneCards and UniProt) and 916 Mus musculus IG and TR genes (with links to MGI and NCBI Gene). The information, for each IMGT/GENE-DB entry, include: IMGT gene functionality, IMGT gene definition (for Homo sapiens and Mus musculus IG and TR), the HGNC gene definition (identical to the IMGT gene definition), number of alleles, chromosomal localization and IMGT/LIGM-DB reference sequence(s) for allele *01. IMGT/GENE-DB is updated weekly, with downloads available in different formats, in the "IMGT downloads" section.
IUIS NOM IMGT-NC Reports for New IG and TR Loci Gene and Allele Names With the increase in genome sequencing and assembly, the starting point for IG and TR gene identification, description and classification has moved from individual sequences (researchers' submission to generalist databases) to the IG and TR locus identification in NCBI Whole Genome Assemblies (WGS) (submitted by sequencing groups and analyzed by researchers). In order to allow researchers to go ahead with expression studies and to publish their data with IMGT gene names even if the loci are not yet been annotated in IMGT ® or in other specialist databases, the IUIS NOM Sub-Committee  [114]  has created the IUIS NOM IMGT-NC Reports. That initiative allows scientists to propose IMGT gene names for new IG and TR variable (V), diversity (D), joining (J) and constant (C) genes and alleles, for a given locus of a given species, to the IUIS Sub-Committee for approval, based on the IMGT Scientific chart rules and the IMGT-ONTOLOGY concepts of classification (CLASSIFICATION axiom).
The submission for an IUIS NOM IMGT-NC Report requires that each gene sequence has an accession number in a generalist database (with localization if large original sequence) and that each V, D, J or C gene sequence has been mapped (cloned from bacterial artificial chromosome (BAC), fosmid, cosmid or phage, or extracted from a referenced genome assembly) (Figure  2 ). 1. For a new V gene and allele, the submitted sequence is that of the L-V-GENE-UNIT: a complete germline genomic sequence (germline gDNA) from the atg (INIT-CODON) of L-PART1 to the V-RS included (http://www. imgt. org/IMGTScientificCh art/SequenceDescription/displayimage. php?id=19) (accessed on 22 February 2022) (Figure  2A ).
These examples of different species and loci have been key elements in the setting of the submission criteria and steps of the now well established IUIS NOM IMGT-NC Reports  [114]. They also confirm the necessity for databases using these data (for analysis or biocuration) to cite and link to the original IUIS report to guarantee interoperability. This is illustrated by the links made to the IUIS reports, in IMGT ® Creations and updates (http://www. imgt. org/IMGTinforma tion/creations/) (accessed on 20 February 2022), following data annotation by the IMGT biocurators for data entry in IMGT ® , as described in Section 6.
These examples of different species and loci have been key elements in the setting of the submission criteria and steps of the now well established IUIS NOM IMGT-NC Reports  [114]. They also confirm the necessity for databases using these data (for analysis or biocuration) to cite and link to the original IUIS report to guarantee interoperability. This is illustrated by the links made to the IUIS reports, in IMGT ® Creations and updates (http://www. imgt. org/IMGTinformation/creations/) (accessed on 20 February 2022), following data annotation by the IMGT biocurators for data entry in IMGT ® , as described in Section 6.
IMGT Locus ID and IMGT/LIGM-DB Locus Reference Sequence An 'IMGT locus ID' comprises the 6-letter (or 9-letter) code from the genus and species (or subspecies) Latin names (IMGT taxon abbreviations), the locus type and a chronological increasing number, separated by underscores, for example, Macmul_IGL_2 (Figure  3 ). An 'IMGT/LIGM-DB locus reference sequence' is an IMGT accession number ('IMGT' followed by 6 digits) which identifies the IMGT/LIGM-DB flat files containing an IG or TR locus (or part of it) extracted from an NCBI genome assembly and presented in its own 5 to 3 locus orientation. As a locus may have, on the chromosome, a forward (or 'Watson') (FWD) or a reverse (REV) orientation (IMGT ® http://www. imgt. org (accessed on 20 February 2022), IMGT Web resources > IMGT Index > Genomic orientation), the sequence orientation in the IMGT accession number flat file is either unchanged (direct) relative to the sequence on the chromosome for an FWD locus, or reverse complemented for a REV locus.
For example, the rhesus macaque (Macaca mulatta) IGL locus orientation on chromosome 10 is reverse (REV) and the IMGT/LIGM-DB locus reference sequence in IMGT000062 is reverse-complement relative to the sequence on chromosome 10. The information from 'Locus in genome assembly' (Figure  3 ) is reported in the definition lines (DE) of the IMGT/LIGM-DB locus reference accession number. For IMGT000062 it includes: Macaca mulatta (Rhesus monkey), taxon:9544, isolate: AG07107 single Indian origin rhesus female, assembly Mmul_10, 2345051 [UID], GenBank assembly ID: GCA_003339765. 3, Refseq assembly ID: GCF_003339765. 1, chromosome 10: CM014345. 1 (29621424-30922134, complement), IMGT locus ID: Macmul_IGL_2.
IMGT LOCUS-UNIT Label and Qualifiers The label IMGT-LOCUS-UNIT (DESCRIPTION axiom) was created to describe a locus, isolated from a genome assembly, in an IMGT accession number flat file. The definition of the IMGT-LOCUS-UNIT and its qualifiers are given in Table  1. Table  1. The IMGT-LOCUS-UNIT label and its associated qualifiers and definitions. Three IMGT/LIGM-DB locus reference sequences for the Macaca mulatta (rhesus monkey) IGH (IMGT000064), IGL (IMGT000062) and IGK (IMGT000063) have recently been created and annotated for the Mmul_10 assembly (GCF_003339765. 1).
IMGT/GENE-DB Localization in Genome Assemblies The section "LOCALIZATION IN GENOME ASSEMBLIES" (Figure  4 ) integrated in 2015 in IMGT/GENE-DB, allows, for a given species and a given locus, to query the IMGT IG or TR genes of a given genome assembly. The query Species: Macaca mulatta|AG07107 (AG07107 is the isolate) and Locus: IGH locus shows the availability of IMGT/GENE-DB biocurated genes for the assembly 'Mmul_10, NCBI', 'Primary Assembly' 'Full chromosome 7′ (Figure  4A ). The results page for the query Species: Macaca mulatta|AG07107 (Rhesus monkey) Locus: IGH (Figure  4B ) provides at the top the chromosome localization: 'chrom 7′, the locus orientation on chromosome 'REV', the number of genes in Mmul_10 (NCBI) (IMGT/GENE-DB annotated genes) '265′ and the number of labels '437′. For each gene, the information comprises IMGT gene name, IMGT gene order, IMGT gene orientation (direct (5′ > 3′) or opposite (3′ > 5′) in the locus), IMGT allele name and Functionality (F, ORF or P), IMGT/LIGM-DB accession number, IMGT labels (L-V-GENE-UNIT and V-RE-GION for a V gene, D-GENE-UNIT and D-REGION for a D gene, J-GENE-UNIT and J-REGION for a J gene, C-GENE-UNIT and C-REGION or the different individual exons for a C gene), IMGT label positions in the IMGT/LIGM-DB accession number, HGNC gene ID (for Homo sapiens), NCBI gene ID (if available), NCBI Mmul_10 Primary Assembly Chromosome (NC) accession number and IMGT label positions in the NC sequence.
For each gene, the information comprises IMGT gene name, IMGT gene order, IMGT gene orientation (direct (5 > 3 ) or opposite  (3 > 5 )  in the locus), IMGT allele name and Functionality (F, ORF or P), IMGT/LIGM-DB accession number, IMGT labels (L-V-GENE-UNIT and V-REGION for a V gene, D-GENE-UNIT and D-REGION for a D gene, J-GENE-UNIT and J-REGION for a J gene, C-GENE-UNIT and C-REGION or the different individual exons for a C gene), IMGT label positions in the IMGT/LIGM-DB accession number, HGNC gene ID (for Homo sapiens), NCBI gene ID (if available), NCBI Mmul_10 Primary Assembly Chromosome (NC) accession number and IMGT label positions in the NC sequence. The list of genes known to belong to the locus but not localized (NL) in the assembly is also provided in this section as this may correspond to polymorphism by copy number variation, insertion/deletion, or gaps in the assembly.
The gene IGHV(II)-20-1 (gene order 129) is an exception as being only represented by a V-RS. Its V-REGION is replaced by the Alu Homo-sapiens_IGH_Alu-20-1 preceded by an undetermined region and the Alu Homo-sapiens_IGH_Alu-20-3 (AC245166 accession number in IMGT/LIGM-DB). N. d: Not defined (for IG and TR). nr: nonrelevant (for RPI). a The CNV3-5prime has been moved to IGHV4-34 (F) upstream in the locus (instead of IGHV3-32 (P) in  [5] ) to select a functional gene as 5prime and include one additional amplification unit, lacking in haplotype F. b No CNV7-3prime has been defined for the Homo sapiens IGH CNV7, owing to the non-identification of a 3 borne for the IGH locus. CNV7 involving V genes are in pale green (CNV1 to CNV6), CNV7 involving C genes is in pale blue (CNV7).
IUIS NOM IMGT-NC Validation of IMGT ® Creations and Updates IMGT ® Creations and updates (http://www. imgt. org/IMGTinformation/creations/) (accessed on 20 February 2022) are published on the IMGT site after completion of the biocuration of new IG and TR loci, genes and/or alleles. The lists of the data for validation by IUIS NOM IMGT-NC comprise: 1. IMGT/LIGM-DB: the creation of the IMGT Locus reference (i. e. , IMGT000062), if relevant, and updates of annotation of previous references sequences. 2. IMGT/GENE-DB: number of genes and alleles per group (IGHV, IGHD, IGHJ and IGHC, or IGKV, IGKJ and IGKC, or IGLV, IGLJ, IGLC), entered in the database, following the annotation of the IMGT Locus reference (with a link to IMGT/GENE-DB update), and FASTA file of the sequences per group.
The IMGT locus, gene order, CNV, haplotypes new concepts have been formalized for the comparison of genomic polymorphisms between different assemblies (chromosomes of individuals) in a given species for entries in databases. These concepts are also used for establishing the IMGT nomenclature of the IG and TR genes of new loci of genome assemblies of new species, differences in gene content in haplotypes, from fish to humans, as recently demonstrated, between strains, for the Salmonid IGH and TRA/TRD loci  [139, 140].
Acknowledgments: We are very grateful to all those who have contributed to building and maintaining IMGT ® , the global reference in immunogenetics and immunoinformatics through these 33 years. We thank  Cold Spring Harbor Protocol Press  for the pdf of the IMGT Booklet available in IMGT references. IMGT ® is a registered trademark of CNRS. IMGT ® is a member of the  International Medical Informatics Association (IMIA)  and a member of the  Global Alliance for Genomics and Health  ( GA4GH ). IMGT ® is granted access to the  High Performance Computing (HPC) resources of Meso@LR and of Centre Informatique National de l'Enseignement Supérieur (CINES) , to  Très Grand Centre de Calcul (TGCC) of the Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA)  and to Institut du développement et des ressources en informatique scientifique (IDRIS) under the allocation  036029  ( 2010-2022 ) made by  GENCI  ( Grand Equipement National de Calcul Intensif ).
Acknowledgements. We thank the anonymous reviewers for the very detailed revision of our work and the Coq formalization. Their comments and suggestions greatly helped us to improve the material of this paper. The work of Olarte was funded by the  Minciencias (Ministerio de Ciencia Tecnología e Innovación, Colombia)  project  PROMUEVA  ( BPIN 2021000100160 ). The work of Pimentel has received funding from the  European Union 's  Horizon 2020 research and innovation programme  under the  Marie Skłodowska-Curie  grant agreement No  101007627.
Genome Dereplication and Selection We first reduced the number of genomes based on genomic signatures  [27]  to regroup similar genomes into genome clusters with a prerelease version of our new software ToRQuEMaDA  [28]. Briefly, for five different k-mer sizes (from 2 to 6-nt), we computed the frequency of each word in each genome using the program compseq from the EMBOSS software package  [29]. The complete lineage of every genome was recovered from the NCBI Taxonomy database [30] using the program fetch-tax. pl from the Bio::MUST::Core distribution (D. Baurain, https://metacpan. org/dist/Bio-MUST-Core, accessed on 16 February 2022). Each signature file was further analysed in R [31] to cluster genomes into a predefined number of groups (300, 600, 900, 1200, 1500 and 2100) using various distance metrics (i.
Supermatrix Assembly To build a robust tree of the bacterial domain, we manually chose a subset of 85 genomes (out of the 903 genomes initially selected), trying to maximize the number of classes. Then, using classify-mcl-out. pl [34] , we selected all orthologous groups of proteins featuring at least one representative of eight major bacterial phyla (Firmicutes, Chloroflexi, Actinobacteria, Deinococcus-Thermus, Proteobacteria, Spirochaetes, Planctomycetes and Bacteroidetes) and in which at most 10% of the selected genomes had more than one gene copy. This left us with a list of 176 broadly conserved and (mostly) single-copy genes. The final dataset was further reduced to 117 orthologous groups to ensure a maximum of 14 missing species in each individual orthologous group (Table  S1 ). The corresponding orthologous groups were aligned with MAFFT v7.
Phylogenomic Analyses For Bayesian inference (BI), we used PhyloBayes MPI v1. 5  [38]  to produce six replicate Markov Chain Monte-Carlo (MCMC) chains of 50,000 cycles, with one tree sampled every 10 cycles, using the CAT+GTR+Γ model of sequence evolution  [39] [40] [41]. Constant sites were deleted with the -dc option. Convergence was assessed using the program tracecomp from the PhyloBayes software package. Two consensus trees (along with their posterior probabilities) were extracted after a burn-in of 10,000 cycles: one over the six chains (A to F) and another over the two most congruent chains (A and C; maxdiff = 0. 130; meandiff = 0. 001), both with the -c option of bpcomp set to 0. 01. Cross-validation tests to decide the bestfit model (CAT+GTR+Γ) were carried out using PhyloBayes v3.
Comparison of the Selected Models Building on the steppingstones sampler files produced by the BayesTraits ancestral state reconstruction, we compared the fit of our five models (in a systematic pairwise fashion) to both the membrane and the peptidoglycan data (used for the ancestral state reconstruction) using Bayes Factors. We selected the steppingstones files from the runs with the tree rooted on the Terrabacteria. As above, the steppingstone sampler used 100 stones with 10,000 iterations per stone.
Evolution of the dcw Cluster 2. 4. 1. Synteny Analyses of Extant Genomes To study the gene order of the dcw cluster across our 903 genomes, we developed a custom R script. This interactive interface allowed us to select any subset of genomes and to focus on any region of the bacterial chromosome chosen as the reference genome for the comparison. To maximize the robustness of these analyses, the data (genomic coordinates, orthology relationships, functions) needed for the visualization are fetched in real-time from the relational database. Examples of graphical outputs produced by this program (limited to the 85 final organisms) are shown in "synteny_85_dcw. pdf" available in the folder ProCARs. The orthologous groups corresponding to the genes of the dcw cluster were identified by a combination of homology searches using reference protein sequences as queries and our R interface for visual confirmation of synteny conservation.
Ancestral Gene Order Reconstruction To reconstruct the evolution of the dcw cluster, we used the program ProCARs  [51] , modified to prevent gene inversions in the cluster (by enabling the -p option). ProCARs input files were built semi-automatically from the relational database, focusing on the 85 bacterial species of our phylogenomic analyses and informed by synteny analyses of extant genomes. Briefly, genes too far from other genes were encoded as lying on different "chromosomes" by introducing artificial telomeres. When several "orthologous" genes were available in a given genome for a specific gene, we first tried to select the gene copy lying on the artificial "chromosome" with the highest count of other dcw genes. If this failed due to ties, we turned to the gene copy located on the main DNA molecule (genuine chromosome or largest scaffold in the genome assembly); otherwise, as a last resort, we selected the gene copy in the same orientation as the dcw genes found on the genuine chromosome or largest scaffold.
If the alignment was good enough, we built an HMM profile from it to search the complete proteomes of our 903 genomes using HMMER  [49, 50]. Then, based on the E-value, length, pHMM profile coverage, copy number and taxonomy of the HMMER hits, we selected the probably orthologous proteins using the visual software Ompa-Pa (A. R. Bertrand and D. Baurain; available at https://metacpan. org/dist/Bio-MUST-Apps-OmpaPa, accessed on 16 February 2022). In contrast, when the alignment of all sequences was too poor, we focused on the original orthologous group containing the E. coli sequence and tried to build a profile by adding up to 6 (for lolB and lptC) of the additional orthologous groups using an iterative strategy as implemented in the software Two-Scalp (A. R. Bertrand and D. Baurain; available at https://metacpan.
Congruence analyses were run on the 117 individual genes using Phylo-MCOA  [44]  and did not reveal incongruent genes or species, beyond 62 individual sequences, which might have experienced gene transfer and/or fast evolution. Once discarded, the overall results did not change, as demonstrated by comparing two control trees (i. e. , before and after outlier removal) inferred with RAxML under the LG+F+Γ model (see Figures  S1  and S2 ). Regarding model selection, cross-validation analyses on four different models confirmed that CAT+GTR+Γ had the best fit to our dataset, followed by CAT+Γ, then GTR+Γ and finally LG+Γ (Table  S5 ). Our unrooted tree is in good agreement with most recent concatenating phylogenomic studies aimed at resolving bacterial evolution  [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] [68].
Some additional phyla initially present in our dataset (i. e. , Synergistetes, Fusobacteria and Aquificae) were excluded from the tree shown in Figure  1  because they were difficult to robustly position (e. g. , due to the chimerical nature of the Aquificae) without bringing more cell-wall architecture diversity (see also  [70] [71] [72] ). Likewise, we further discarded the Thermotogae, which are also chimeras  [70] , even though their toga might be akin to a modified outer membrane  [73, 74]  (see Figure  S6  for a preliminary 101-species tree including all these lineages). Such uncertainties are not uncommon in bacterial phylogenomics and are the result of a combination of weak phylogenetic signal, widespread lateral gene transfer and systematic error (e. g. , long-branch attraction artifacts)  [72, [75] [76] [77] [78] [79] [80] [81] [82].