dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgements We kindly appreciate the support from the  ELTE   Thematic Excellence Programme 2020  supported by  National Research, Development and Innovation Office - TKP2020-IKA-05  and the  Tempus Public Foundation for the Stipendium Hungaricum Scholarship funding  provided to M. Y. This work was supported by  French-Hungarian and Japanese-Hungarian Intergovernmental program of National Research, Development and Innovation Office  ( 2018-2. 1. 13-TÉT-FR-2018-00007and TÉT_12_JP-1-2014-0023 , respectively). S. F. , S. S. , and F. H. acknowledge the  Collaborative Research Program  of the  Institute for Chemical Research, Kyoto University  (Grant Numbers  2017-91 ,  2018-98  and  2018-100 ).
Analysis of fragmentation spectra suggested that the bioactive compound may be a RiPP with its precursor a peptide containing an (I/L)TTTWTVTTTGVWA sequence. We sequenced, assembled, and annotated the genome of B. thuringiensis sv. andalousiensis NRRL B23139 (GenBank: NZ_CP035727. 2). Using the predicted partial sequence of the bioactive peptide as a query for BlastP search, we identified a compact locus containing seven short open reading frames (ORFs), whose products matched the predicted partial sequence of the bioactive RiPP. Five of the seven genes code for identical 45-amino acid-long peptides (AncA1-2, AncA4-6), whereas two genes encode peptides harboring an alanine to valine substitution in the putative leader (AncA3) and in the core (AncA7) parts, respectively (Figure  2D ). A gene encoding a class III lanthionine synthetase is located upstream of the peptide-coding locus.
, 2006). We identified conserved motifs in predicted precursor sequences using MEME software  (Bailey et al. , 2009). As expected, the class III leader peptide motif VLXLQ (motif 1 in Figure  7C ) and labionin motifs S(X) 2 S(X) 2 C or S(X) 2 S(X) 3 C were found (motifs 3 and 5, Figure  7C ). Almost half of the precursors contained an extended tandem labionin motif (motif 2 in Figure  7C ). We also identified an additional motif enriched in threonine residues (Figure  7C , motif 4) previously noted by  (Walker et al. , 2020). Mapping of predicted precursor peptide motif architectures to the LanC phylogenetic tree revealed, remarkably, that precursors with different motif architectures are associated with distinct clades. Precursors presumably containing two labionin macrocycles, either extended tandem motif 2 or various combinations of motifs 3 and 5, are associated with the basal clades of LanKC enzymes.
The accuracy of the obtained masses was within 0. 1 Da. Spectra of fragmentation were obtained in LIFT mode; the accuracy of product ions measurement was within 1 Da range. Mass-spectra were processed using FlexAnalysis 3. 2 software (Bruker Daltonics, Germany) and analyzed manually. For high-resolution mass spectrometry andalusicin A was diluted to 0. 5 mg/mL in 0. 1% formic acid/ 25% acetonitrile. The exact mass was measured on FTICR MS Apex Ultra (Bruker Daltonics). The NMR sample was prepared by dissolving 3. 5 mg of andalusicin in 200 ml DMSO-d6 (Sigma-Aldrich, US), and after adding 1 mM of TMS for spectral referencing, it was introduced in a 3mm NMR tube. All spectra were recorded at 30 C on an 800 MHz AvanceIII NMR spectrometer equipped with a cryogenic QCP probe head (Bruker, Billerica, USA).
QUANTIFICATION AND STATISTICAL ANALYSIS Statistical analysis was performed in Python 3. 7 using SciPy 1. 3. 1  (Virtanen et al. , 2020)  and statsmodels 0. 10. 1  (Seabold and Perktold, 2010)  packages. The proportion of cells with the compromised membrane was calculated by manual counting the PI-positive and DAPI-positive cells. At least 3 independent measurements were performed for each of the inhibitors (Table  S2 ). First, we compared the replicates using Fisher's exact test. For all inhibitors, we found no difference between replicates at the significance level 0. 05 (with Bonferroni multiplicity correction). Thus, we pooled the replicates and conducted another series of Fisher's exact tests with Bonferroni adjustment and the significance level 0. 05. No significant difference was observed only between negative control (DMSO) and CCCP samples.
Software and algorithms ImageJ  (Schneider et al. , 2012)  https://imagej. nih. gov/ij/ SPAdes v. 3. 9. 1  (Bankevich et al. , 2012)  https://cab. spbu. ru/software/spades/ RAST (Overbeek et al. , 2014) https://rast. nmpdr. org/rast. cgi MEME Suite v. 5. 0. 2 (Bailey et al. , 2009) https://meme-suite. org/meme/tools/meme EFI-EST (Gerlt et al. , 2015) https://efi. igb. illinois. edu/efi-est/ Cytoscape (Shannon et al. , 2003) https://cytoscape. org/ MMseqs2 version 12. 113e3 (Steinegger and So ¨ding, 2017) https://github. com/soedinglab/MMseqs2 MUSCLE v3. 8. 31 (Edgar, 2004) http://www. drive5. com/muscle/ ClipKIT v1. 0. 7 (Steenwyk et al. , 2020) https://github. com/JLSteenwyk/ClipKIT RaxML (Stamatakis, 2014) https://cme. h-its. org/exelixis/web/software/raxml/ Batch CD-Search (Lu et al. , 2020) https://www.
ncbi. nlm. nih. gov/Structure/bwrpsb/ bwrpsb. cgi iTOL (Letunic and Bork, 2019) https://itol. embl. de/ SciPy v. 1. 3. 1 (Virtanen et al. , 2020) https://www. scipy. org/ statsmodels v. 0. 10. 1 (Seabold and Perktold, 2010) https://www. statsmodels. org/stable/index. html custom scripts for bioinformatic analysis This study https://github. com/bikdm12/andalusicin.
ACKNOWLEDGMENTS We are grateful to Dmitry Travin (Skoltech, Russia) and Dmitry Ghilarov (Jagiellonian University, Poland) for the critical reading of the manuscript. We thank Tatyana Smirnova and the Center for Precision Genome Editing and Genetic Technologies for Biomedicine, IGB RAS (Moscow, Russia), for microscopy. We thank Dr. Viktor Zgoda and ''Human Proteome'' Core Facilities of the Institute of Biomedical Chemistry (Moscow,.
thuringiensis sv. andalousiensis NRRL B23139 was extracted with GeneJET Genomic DNA Purification Kit (ThermoFisher Scientific, USA) according to the manufacturer's protocol. The library was prepared using NEBNext Ultra II kit (New England Biolabs, USA) and sequenced using HiSeq platform (Illumina, USA). Genome assembly was performed using SPAdes v. 3. 9. 1  (Bankevich et al. , 2012)  with B. thuringiensis HD521 genome sequence (GenBank: CP010106. 1) (Li et al. , 2015)  as a reference. Genome annotation was performed using RAST software  (Overbeek et al. , 2014). Genes encoding andalusicin precursor peptides were identified using BLASTp against products of all ORFs with a partial sequence of the peptide predicted by MALDI-TOF-MS/MS used as a query.
Bioinformatic analysis A dataset of LanKC sequences and corresponding automatically predicted precursor peptides was retrieved from work by  (Walker et al. , 2020). 1,646 class III LanKC sequences were acquired from the NCBI Protein database (https://www. ncbi. nlm. nih. gov/protein/). The sequence of andalusicin LanKC (AncKC) was added, and the resulting dataset was used for a sequence similarity network construction using the EFI-EST web tool  (Gerlt et al. , 2015)  with a strict alignment score cutoff (130, equivalent to an e-value of 10 -130 ). For visualization of the network, the Cytoscape program was used  (Shannon et al. , 2003). The cluster (connected component) containing AncKC was selected for further analysis (Group II, Figure  7A ). Another cluster (Group IV, Figure  7A ) consisting mainly of LanKC from Firmicutes was also included in phylogenetic reconstruction to serve as an outgroup for tree rooting.
All proteins encoded within 10 kbp upstream or downstream to the lanKC present on the tree were obtained from RefSeq database on February 2021 (https://www. ncbi. nlm. nih. gov/refseq/) and functionally annotated using conserved domain database (CDD) database via Batch CD-Search web server  (Lu et al. , 2020). Dataset for de novo motif discovery consisted of the precursor peptides associated with all LanKCs from the network clusters selected for the phylogenetic analysis. For LanKCs shown on the tree, the prediction of ORFs encoding potential precursor peptides was refined manually (Table  S4 ). An ORF was considered as encoding a precursor peptide if it was preceded by a strong ribosome binding site, was located in the proximity to lanKC, and its product harbored characteristic leader motif LxLQ described previously  (Mu ¨ller et al.
, 2011). Prior to motif discovery the duplicates were removed from the dataset via clustering with MMseqs2 (Steinegger and So ¨ding, 2017) with 95% identity and 95% coverage cutoffs. Motifs in the representative precursor peptide sequences were identified using MEME v5. 0. 2  (Bailey et al. , 2009)  with the following parameters: any number of sites per sequence, minimum motif width 6, maximum width 60, and 30 minimum sites per motif. Manually predicted sequences of precursor peptides associated with LanKCs present on the phylogenetic tree were then scanned for the presence of motifs with MAST  (Bailey et al. , 2009)  using per sequence composition in significance calculation and omitting motifs with e-value greater than 0. 05. The phylogenetic tree, along with gene co-occurrence and precursor peptide motif architectures was visualized using iTOL  (Letunic and Bork, 2019).
Study Design and Patient Population This prospective, randomized, double-blind, placebo-controlled study was registered at ClinicalTrials. gov under the ID: NCT02997059, 19 December 2016  [31]  where all details of the study are provided. In brief, patients were enrolled between 2009 and 2015 in Lille University Hospital, France. Patients were eligible for the study if they were ≥18-years-old, with ileal or ileo-colic CD, with surgical resection of all macroscopic damage and with a pre-operative ASCA level of ≥50 arbitrary units (AU) (IBDX kit; Glycominds, Lod, Israel) in the month before inclusion. The main exclusion criteria were: pregnancy or no effective contraception, cumulative ileal surgical resection of more than 1 m or subtotal colic resection, hypersensitivity to FCZ or other azoles, and liver or renal failure.
Statistical Analysis All statistics and figures were computed with R statistical open-source software, SAS 9. 4 (SAS Institute, Cary, NC, USA), and GraphPad Prism v6. 0. Software GraphPad Software Inc. , San Diego, CA, USA Categorical variables are expressed as number (percentage). Quantitative variables are described as median and interquartile range (IQR). Normality was assessed by the Shapiro-Wilks test combined with graphical evaluation (QQplot). First, exploratory univariate analyses were performed to assess the evolution of each biomarker after surgery by comparing the value at inclusion with the value at the end of the study (6 months) using the paired Student's t test in case of normality and the non-parametric rank signed test otherwise. These analyses were adjusted for the level at inclusion.
In case of non-normality of biological parameters, these analyses were performed on log-transformed data in case of log-normality and on rank data otherwise. Correlations between biological parameters are given by the Pearson or Spearman coefficient of correlation depending on the distribution of the parameters. Considering the exploratory nature of theses analyses, all statistical tests were performed at the two-tailed α level of 0. 05 and the results should be interpreted as hypothesis-generating. Second, statistics and figures were computed with the "R/Bioconductor" statistical open-source software [58]. Biomarkers were described by median and IQR. In order to guarantee normally distributed data, each biomarker data has been transformed using Box-Cox transformation  [59]. A differential analysis was carried out using the most appropriate test between paired Wilcoxon signed-rank test or paired student t-test according to normality and sample variance distribution.
1 , SI Appendix D2). Analysis revealed that 57. 4% of the 2410 CDSs were highly expressed (in the upper quartile of expression level) in at least one sample of the dataset. Only 5. 8% (136) were highly expressed in all samples including typical housekeeping genes encoding ribosomal proteins and carbon metabolism enzymes, but also those encoding the TonB-ExbBD system, several outer membrane proteins, the T9SS core components and gliding motility proteins (Table  S4 ). Only 4. 4% (103) of the CDSs, mostly of unknown function, showed low expression in all samples. High congruence between biological replicates allowed to identify differentially expressed genes between conditions: 86% CDSs were found differentially expressed in at least one comparison (SI Appendix T4, Table  S5 ). Taken together, these numbers indicate good coverage of the expression space.
Characterization of promoters and alternative sigma factor regulons The 1884 genomic positions identified as putative primary 5′-ends by 5′-end RNA-Seq (SI Appendix D3) were further analyzed to establish a list of high-confidence TSSs and to identify high-level transcriptional regulation by sigma factors, the transient subunits of bacterial RNA polymerase responsible for recognition of promoter sequences. Besides the primary sigma factor, hereafter named σ A , the F. psychrophilum genome contains 8 alternative sigma factors: 1 σ 54 and 7 extracytoplasmic function (σ ECF ) sigma factors, some of them induced in specific conditions such as plasma exposure and high osmotic pressure (SI Appendix D4). The dataset was analyzed for de novo identification of sigma factor binding sites by combining information from DNA sequences, 5′end positions and condition-dependent expression profiles  [37].
This is consistent with our findings in F. psychrophilum. Transcriptional activation by σ 54 strictly depends on enhancerbinding activators. Since three proteins containing a σ 54 interaction domain (PF00158) were predicted in the genome, coexpression clusters within SM4 promoters might correspond to distinct activators sensing different environmental signals. Motif SM5 is characterized by a TAnnTTGY box at the same position (-12 to -5 bp) than the σ A consensus TAnnTTTG. A striking similarity is the presence of highly conserved elements TA and TTG, but the distance between them is 1 bp shorter in SM5. Accordingly, guanidine at -6 and pyrimidine at -5 are specific of SM5 promoters. Transcribed genes are related to LPS biosynthesis, amino-acids scavenging and gliding motility (Table  2B , SI Appendix D5).
The conditiondependent transcriptome dataset confirmed expression of at least 87% of the TRs (Table  3 ; SI Appendix D1). • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • T1 T2 T3 T4 T5 Antisense RNAs. Overall, 287 TRs overlapping the antisense strand of 281 CDSs were detected. This represents 12% of the total number of CDSs and very diverse biological functions (Table  S6 ). Antisense RNAs (asRNAs) originated mostly from imperfect termination of transcription and from transcription initiation at non-canonical locations, as exemplified by the high proportion of asRNAs in 3′, 3′PT, and indep TR categories (Table  3 , SI Appendix D7). Such antisense transcription patterns have been reported in a wide range of bacterial species and is referred to as pervasive transcription.
migale. inrae. fr/structural_annotation. html. located in sense or antisense of the TRs and many were not in TRs. A number of structured 5′ elements identified for the first time in this study were conserved outside the species. Some are present in other genera of the family Flavobacteriaceae (e. g. the 5′ elements upstream of pheA, hisG, ftsY, acsA, alaS, or rimP). Without hits in the RFAM database, they probably represent original cis-regulatory elements whose study may be of great interest. Small regulatory RNAs. A total of 4 known RNAs (small signal recognition particle RNA, RNase P, transfer-messenger RNA and 6S RNA) and 85 newly described RNAs (indep TRs), named Rfp1-89, were detected (Table  S8 ). Indep TRs were typically short (median length, 176 bp) and without coding potential; 40 were transcribed in antisense of CDSs, with a potential cis-regulatory effect (Table  3 ).
ACKNOWLEDGEMENTS This work was financially supported by the  Agence Nationale de la Recherche  (grant  ANR-17-CE20-0020-01  FlavoPatho). We thank  Marco Moroldo ,  Jérôme Lecardonne , l and the  INRAE GABI-CRB Bridge  platform for microarray services,  Brigitte Kerouault  and  Victor Folcher  for excellent technical assistance. We thank  David Halpern  and  Philippe Bouloc  for helpful discussions and warm support, and  Claire Morvan  for critical reading of the manuscript. This work has benefited from the facilities and expertize of the high throughput-sequencing platform of IMAGIF (http://www. i2bc. paris-saclay. fr/), the  INRAE MIGALE bioinformatics facility  (https:// doi. org/10. 15454/1. 5572390655343293E12 ),and the MicroScope annotation platform for computational resources. The authors are grateful to the staff of the  INRAE IERP  fish facilities.
Background Human endogenous retroviruses (HERVs) are aberrantly expressed by tumor cells and may represent a source of T cell epitopes Methods Using TCGA pancancer RNAseq data (n=8,893 samples), we developed a bioinformatics-based method to select cancer-specific HERVs associated with a cytotoxic T cell response ("cyt-HERVs") and identify shared T cell epitope candidates. T cells were primed with selected short and long peptide candidates from HLA-A2+ healthy donors. Peptidespecific dextramers were used to sort and expand specific CD8+ T cell clones and determine their TCR sequences and avidity. Cytotoxicity was assessed against HERV-expressing tumor cell lines and patient-derived organoids using Incucyte and Nanolive technologies (Flowchart, figure  1 ). Results In a pancancer analysis, we identified 57 HML-2/ HERV-K HLA-A*0201 epitope candidates from 27 distinct open reading frames.
Six shared HLA-A2 strong binders 9-mer peptides, present on multiple HERVs located on different chromosomes, and with translational evidence found in mass spectrometry public datasets, were selected and synthetized. In vitro HLA binding assay confirmed peptide-HLA affinity. Priming assays showed the presence of specific CD8+ T cells leading to polyfunctional IFN-g+ TNF-a+ T cell responses with upregulation of the degranulation marker CD107A upon co-culture with peptide-pulsed T2 cells. Synthetic long peptides containing the epitopes were used to confirm the correct processing by antigen-presenting cells. The functionality of the sorted T cell clones was confirmed using an Elispot assay (GrzB+ IFN-g+). Their sequenced TCRs were predicted to stably interact with their respective MHC-peptide complexes in a 3D model.
This particular case could also be the result of a new infection with serological traces of a previous infection, as leptospiraemia is known to last only a few days  [7]. In E36, leptospiral DNA was detected in the kidney sample, and the MAT titre was 1:40. This is indicative of an old infection and chronic carriage. E32 exhibited the same situation, but DNA was also detected in the urine, which is indicative of intermittent urinary excretion. Finally, for E19, leptospiral DNA was detected in the kidney sample, but PCR could not be performed with the urine sample from this animal. The PCR results showed a significant difference between the two populations, with 12/42 positive results for stray cats compared with 0/50 in domestic cats. These data must be considered carefully for several reasons.
Statistical analysis Survival curves were estimated using the Kaplan-Meier method and were compared by a log rank analysis using the online platform BiostaTGV. Firstly, survival curves for each replicate within condition of infection were compared, and if no significate difference was observed, the two series were pooled to represent the viral infection condition. In case of significant difference, each replicate was analysed separately and compared to the other conditions of infection. In addition, Mean Day to Death (MDD) was calculated by Kruskal-Wallis test combined with a Dunn's post hoc test to compare the 5 infected conditions (XLSTAT 2020). Statistical analyses were performed using XLSTAT statistical software (2019), with a significance level of 5%. Immune parameters of control and infected fish were evaluated using a two-way analysis of variance (ANOVA), taking into account the strains and sampling date for each sample.
Acknowledgments Firstly we would like to thank  Evelyn Emmenegger , from the  Western Fisheries Research Center, Seattle , who kindly accepted to provide us a set of 24 strains of IHNV, among which five were used in the study described here. We sincerely thank the  NGS Platform at ANSES  located in Ploufragan for partial and full length sequencing. The authors would like to thank  Craig Stevens , MA, DESS,  ELS (Coup de Puce Expansion ; http://www. coupdepuce. com)for the English language review.
1 Cycle Sequencing Kit in an ABI Prism 3100 Genetic Analyser (Applied Biosystems, Villebon-sur-Yvette, France) with nine sequencing primers designed using Geneious 9. 1. 8 software. Their specificity was assessed by comparison with GenBank ®. The sequencing results were analyzed using the Geneious 9. 1. 8 software by comparison with the AD169 UL52 sequence.
Heatmap Generation The heatmap provides a data matrix where the coloring gives an overview of mutational differences between strains. Python 3. 9. 6 engine is used to generate this binary heatmap. The strains groups are extracted from the base dataset, and the nature of the mutation is recorded in a dummy variable. The base dataset is converted into a twodimensional matrix (x,y) with y the "strain" ordered by group and x the "amino acids" ordered by "amino acids" id. The binary heatmap is plotted to show mutations in saddle brown and the absence of a mutation in peach puff.
Identification of Sequence Polymorphisms The pUL52 sequence of reference strains AD169, Towne and Toledo were identical to the sequences found in GenBank (accession number FJ527563. 1, GQ121041. 1, GU937742), and inter-assay reproducibility was 100%. Among the 61 naïve strains sequenced, we described 36 amino acid polymorphisms distributed across pUL52. Seven are also present in the reference strains Towne, Toledo, Davis or Merlin. The mean identity of the HCMV isolates was 99. 4% (range: 98. 2-100%), and the mean number of polymorphisms per isolates was 3. 4 (range: 0 to 12). Analysis of polymorphism repartition through pUL52 revealed two parts with a huge concentration of mutations which are consistent with the alignment where gaps and variability were found. These two variable regions are annotated as pUL52 VRI and VRII.
pUL32 Polymorphism Is Consistent with pUL52 The polymorphism of the HSV-1 pUL32 protein, the HCMV pUL52 homolog, was studied from 44 different strains found in Genbank ® : 42 mutations were found through the 596 amino acids that composed pUL32. The polymorphism distribution reveals a variable region from amino acid 0 to 100 and a second longer variable region from amino acid 250 to 390 (Figure  2a ). These two variable regions are consistent with the regions described in pUL52. Four motifs, 128 CXXC 131 , 155 CXXC 158 , 423 CXXC 426 and 495 HXXCXXXC 502, described by Albright et al. , are not in polymorphism-rich regions and are conserved between the three Herpesvirus subfamilies  [16]. Only the 291 CXXXXC 297 motif is located in a polymorphism-rich region that we called VRII. This motif is only found in alphaherpesviruses (Figure  2b ).