dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgments Laurence Emond for F-Actin sample preparation and immunocytochemistry. Francine Nault ,  Charleen Salesse  and  Laurence Emond  for the neuronal cell culture. Jonathan Marek  and  Renaud Bernatchez  for the development of a custom Python annotation application. Thibault Dhellemmes for inter-expert axon DAB annotations in electron microscopy images. Christian Gagné  and  Marc-André Gardner  for preliminary discussion on semantic segmentation. Annette Schwerdtfeger  and  Ana Gabela  for careful proofreading of the manuscript. Funding was provided by grants from the  Natural Sciences and Engineering Research Council of Canada  (P. D. K. and F. L. C. ),  Canadian Institutes of Health Research  (P. D. K. ),  Neuronex Initiative (National Science Foundation and Fond de recherche du Québec -Santé ) (P.
Data and code availability The MNIST, Cell Tracking Challenge, and P. Vivax datasets are all publicly available online. The F-actin dataset is available at the following website: https://s3. valeria. science/flclab-micranet/index. html. The Electron Microscopy dataset included in this study is available from the corresponding author upon reasonable request. All relevant material related to this paper is available on the following website: https://s3. valeria. science/flclab-micranet/index. html. Open source code for the MICRA-Net approach is available online: https://github. com/FLClab/MICRA-Net.
4. 2. 1 2. 212 Modified MNIST datasetWe generated the modified MNIST training dataset by randomly sampling N digits from the original MNIST training dataset and randomly distributed them on a 256 × 256 pixel field of view. To avoid overlap between digits we used a random Poisson disc sampling algorithm with a radius size of 25 pixels [55]. The number of digits N was uniformly sampled from {1, 2, 3, 4, 5, 10, 15, 20, Max}, where Max corresponds to the maximum number of digits that can be placed without overlap. A rotation of ±30 • uniformly sampled was applied to the digits before placement on the image. We applied, in a random order, a Gaussian blur with sigma uniformly sampled in [0, 2[ and artificial normalized Poisson noise with λ = √ 255 The resulting image intensities were clipped to lie in [0, 1].
4. 5 In-house datasets acquisition 4. 5. 1 5451 Cell culture, Immunostaining and STED imaging for F-actin imaging Before dissection of hippocampi, neonatal Sprague Dawley rats were sacrificed by decapitation, in accordance to the procedures approved by the animal care committee of Université Laval. Dissociated cells were plated on poly-d-lysine coated glass coverslips, fixed and immunostained as described previously [2]. F-Actin was stained with Phalloidin-STAR635 (Abberior GmbH, Germany). Dendrites Microtubule-Associated-Protein (MAP2) [2]. STED images of the F-Actin nanostructures were acquired on a 4 color Abberior Expert-Line STED microscope (Abberior Instruments GmbH, Germany), equiped with a 100x 1. 4 NA oil objective and using pulsed (40 MHz) excitation (640 nm) and depletion (775 nm) lasers.
Fluorescence was detected with an Avalanche Photodiode (APD) and a ET685/70 (Chroma, USA) fluorescence filter. Pixel size was set to 20 nm. 4. 5. 2 Animals and stereotaxic injections for scanning electron microscopy datasetThis study was carried out on 3-month-old mice, weighing 25-35g. Animals were housed under a 12h lightdark cycle with water and food ad libitum. All procedures were approved by the Comité de Protection des Animaux de l'Université Laval, in accordance with the Canadian Council on Animal Care's Guide to the Care and Use of Experimental Animals (Ed2), and with the ARRIVE guidelines. Maximum efforts were made to minimize the number of animals used. Transgenic e-Pet Cre mice expressing Cre recombinase under the control of Fev promoter, known to be specific for serotonin (5-HT) neurons [59] , were injected in the dorsal raphe nucleus (DRN) with 1 µl of AAV9-CAG-DIO-APEX2NES-WPRE.
Data description In this study, we collected PacBio CLRs (ERR5487554 -ERR5487559), HiFi reads (ERR5485301), Illumina paired-end (PE) sequencing reads (hereafter referred to as Illumina PE reads) (ERR5484652), and Hi-C data (ERR5484651) for the African cassava cultivar TME204. It belongs to a group of cassava cultivars carrying the dominant monogenic CMD2 resistance locus, which provides resistance to Cassava Mosaic Diseases (CMD) caused by African Cassava Mosaic Viruses  [21]. We benchmarked the performance of CLRs and HiFi reads in assembling this highly complex and heterozygous genome. Assembly continuity, accuracy, and haplotype resolution of different genome drafts produced by four CLR/HiFi assemblers  [14, 18, 22]  were evaluated using genome quality metrics proposed by the VGP consortium  [23]  with Illumina PE reads from the same sample.
Our results demonstrate that HiFi reads are valuable in assembling a high-quality heterozygous and repetitive plant genome. The high base accuracy and long sequencing read length provide superior resolution and accuracy in resolving allele differences between haplotypes, paralogous genes and repeat elements. By combining HiFi reads with Hi-C data we produced a highly accurate, chromosomescale, phased assembly for a diploid African cassava cultivar. The two haploid assemblies (PRJNA758616 and PRJNA758615) revealed extensive haplotype heterozygosity within a cassava diploid genome and provided for the first time a systematic view of the cassava diploid genome organization. To improve genome annotation, we further generated PacBio Iso-Seq reads (ERR5489420 -ERR5489422) from different tissues.
1 ). To assess the performance of different assemblers, the HiFi reads were assembled using four HiFi-specific software tools: Falcon, HiCanu, hifiasm and IPA (see Materials and Methods). For comparison of the HiFi reads with traditional long reads, we also assembled 121x PacBio CLRs (Table  1 ) from the same DNA sample using the Falcon assembler. In the case of a heterozygous, diploid genome such as cassava, diploid-aware assemblers (Falcon, hifiasm and IPA) produce a primary genome assembly, which is a set of primary contigs representing pseudo-haplotypes (the longest continuous stretches of assembled sequences), and an alternate assembly consisting of a set of unphased associated contigs (Falcon) or phased (IPA, hifiasm) haplotigs (i. e. , continuous sequences of the same haplotype). For a genome with very high sequence divergence between haplotypes, haplotype allelic contigs can be incorrectly placed in the primary assembly, resulting in heterotype duplications that inflate the assembly size  [23, 25].
CLR-Falcon assembly took a few weeks and used about 7 TB of disk space. The CLR-Falcon contig N50 of TME204 was already 10-fold longer compared to cassava TME3 and 60444 CLR-Falcon contigs  [8] , although the three genomes have similar levels of repetitiveness and heterozygosity (Supplementary figure  1 ). This could be due to longer sequencing read length, more accurate sequencing chemistry and base calling algorithms, higher coverage (Table  1 ), and the improved version of the Falcon assembler. HiFi reads improved contig continuity further, doubling contig N50 and NG50 values when assembled using Falcon (Figure  1 b ). Assembled genome sizes varied based on the assembly software (Figure  1  a), thus N50 values cannot be used for comparisons between assemblers since they depend on the assembly size.
997%, quality value (QV) 46. 74) and complete (98. 40%) (Figures  1 c, d  and g ). The consensus accuracy measured using the aligned Illumina PE reads was lower than the measurement using k-mer analysis, while completeness measured using mapped Illumina PE reads was higher. The sequence differences between the mapped Illumina PE reads and the assembled consensus sequences could originate from sequencing errors in the Illumina reads and/or mis-alignments introduced by the alignment software tool. The read alignment process is also more tolerant to sequencing errors than the k-mer analysis, where erroneous k-mers were identified and excluded. Consequently, hereafter we only used k-mer analysis  [27]  to measure the accuracy and completeness of the genome sequence assemblies. Because a correct assembly of PacBio CLR reads requires signal level polishing to achieve satisfactory consensus accuracy  [28] , we further phased and polished the CLR-Falcon assembly using Falcon-Unzip  [22].
The total size of TME3 and 60444 assemblies could be decreased to around 750 Mbp with purge_haplotigs  [25] , a tool that identifies and removes allelic variants in the primary assembly, confirming that the large assembly size was mainly caused by heterotype duplications  [8]. For the HiCanu and hifiasm TME204 assemblies, the total sizes were both about twice the haploid genome size, with more than 80% of the single-copy orthologous genes in the BUSCO plant database being duplicated (Supplementary table 2), indicating that they captured alleles from both haplotypes. Falcon (HiFi and CLRs) and IPA produced smaller assemblies, with lower numbers of duplicated BUSCO genes, further indicating they collapsed more haplotype alleles. Merqury k-mer analysis  [27]  confirmed that the assemblers varied in their performance of resolving haplotypes in the TME204 genome.
Phased, haplotype-resolved contigs of cassava TME204 Subsequently we used a newer release of the hifiasm assembler (v0. 15. 2) to assemble the haplotype-resolved TME204 contigs, which were also phased at the same time using Hi-C technology (   2 ). This would be expected for a completely haplotype-resolved genome assembly in which even homozygous segments of the genome are included in both haplotypes. Only 3% of k-mers were from artificial duplications (Figure  2 ), which was similar to the false duplication rates measured at approximately 1% (reference asmgene score) to 4% (BUSCO duplication score). Functional completeness measured using plant BUSCO orthologs and TME204 Iso-Seq transcripts was 98% and above. The reference asmgene completeness score was slightly lower (95%). The slightly lower asmgene scores could be due to the high level of sequence differences between AM560 and TME204 (see later comparative analysis), therefore fewer AM560 reference genes could be aligned to TME204, resulting in lower asmgene completeness and duplication scores.
It is clear that these haplotigs are of cassava origin and not from foreign contamination. When the assembled sequences were screened against the NCBI (National Center for Biotechnology Information) mitochondrial database, unanchored haplotigs representing the highly fragmented mitochondrial genome were identified in both haplotype assemblies (Table  3 , Supplementary figure 4 a). When compared to the other none mitochondrial unanchored haplotigs, mitochondrial haplotigs have a smaller size variation (25-76 kbp) and lower depth of coverage on average (Supplementary figure  4 b ). Regions similar to nuclear mitochondrial pseudogene regions (numt's) were also ubiquitous and found in both pseudochromosomes (Supplementary figure  4 c ) and unanchored haplotigs (Supplementary table  6 ). Some of the none-mitochondrial unanchored haplotigs can be regions still missing from the current set of pseudochromosome pairs where the gene content completeness ranges from 91 to 98% (Table  3 ).
After adapter ligation, DNA was PCR-amplified and purified using SPRI beads. The purified DNA was quality-controlled using qPCR (Roche) and Bioanalyzer (Agilent Technologies), then sequenced on the Illumina HiSeq X following manufacturer's protocols, yielding 727,211,240 read pairs (2X150 bp) (Accession number: ERR5484651).
PacBio CLR reads were then aligned to each haploid genome and the coverage was analyzed using Asset software (https://github. com/dfguan/asset). Assembled regions supported by 10 and more PacBio CLR reads were identified as reliable regions. Functional completeness was measured using BUSCO (v5) completeness of single-copy orthologs discovered in plants (Viridiplantae Odb10)  [63] , and alignment rates of reference genes and TME204 Iso-Seq transcripts. The AM560 reference genome (v8. 0) and gene annotation (v8. 1, https://phytozome-next. jgi. doe. gov/info/Mesculenta_v8_1)  [30]  were downloaded from JGI Phytozome 13 (https://phytozome-next. jgi. doe. gov/)  [64]. Reference coding sequences (CDSs ) were aligned to the AM560 reference genome and TME204 haplotigs using minimap2 (v2. 15r905,cxsplice -C5)  [65].
"asmgene" completeness and duplication scores  [18]  were calculated using the "paftools" script from the minimap2 package, based on CDSs mapped at ≥97% identity over ≥99% of the CDS length. Iso-Seq data collected from TME204 transcriptomes of fibrous root, stem meristems and leaves were spliced aligned using minimap2 (v2. 15r905, x splice:hq). Alignment statistics were collected using alignqc  [66].
Construction of Pseudochromosomes Hi-C reads were mapped back to each set of haplotigs independently using the Arima mapping pipeline (https://github. com/ArimaGenomics/mapping_pipeline) and were used to further scaffold haplotigs with SALSA2 (v2. 2, assisted by the assembly graph, resolved mis-assemblies, five iterations)  [68]. No haplotigs in TME204 H1 were further scaffolded with Hi-C data after five rounds of iteration (Supplementary file 1). Thirty haplotigs in TME204 H2 were scaffolded into 13 scaffolds, of which seven were chromosome-scale and consistent with the genetic map (Supplementary table  5 ). One scaffold was apparently a technical artifact based on genetic markers, reaching 107 Mbp long and joining haplotigs together from chromosomes I, XVI and XVIII (Supplementary table  5 ).
Finding extra copies of the same genes was enabled with a minimum sequence identity of 95% in exons/CDSs. Synteny analysis of orthologous pairs of transferred genes was performed using MCScanX  [80]  and visually inspected using accusyn (https://accusyn. usask. ca/). PacBio Iso-Seq reads from the three different TME204 tissue types were clustered into high quality (accuracy 99. 9%, HQ) transcripts using the Iso-Seq Analysis Application in PacBio SMRT Link software (10. 1. 0. 119588). HQ transcripts from different tissues were pooled and aligned to each haplotype assembly. Redundant isoforms were collapsed into 36,000 unique transcripts using cDNA_Cupcake (https://github. com/Magdoll/cDNA_Cupcake/). Unique transcripts were quality-controlled, filtered and classified using SQANTI3 (v4. 1)  [81]  to identify novel transcripts and gene models.
Differential expression of transcripts and analysis of allele-specific expression Transcript sequences annotated in TME204 H1 and H2 were pooled and de-duplicated using cd-hitest (v4. For allele-specific expression (ASE), bi-allelic transcripts were identified by a combination of reciprocal blastn comparison of H1 and H2 transcripts and gene synteny. Among all transcripts associated with an orthologous gene pair, transcripts of reciprocal blastn best hits were considered as allele A and B. Expression values for bi-allelic transcripts were subset from the master quantification table including all resolved alleles, ASE was determined using the same package DEseq2, with adjusted p-value <0. 05.
Structural variant analysis using HiFi reads TME204 HiFi reads were aligned to reference contigs of AM560 and TME204 haplotigs using minimap2 (v 2. 15r905). SVs were called using PacBio structural variant calling and analysis tools (PBSV, https://github. com/PacificBiosciences/pbsv). Summary statistics of SVs were collected using SURVIVOR (v1. 0. 7).
Acknowledgments We thank the high-throughput sequencing team at  FGCZ  for Illumina sequencing service,  Arima Genomics  for Hi-C service,  Dr. Daivd Stucki  and  Deborah Moine  from  PacBio  for their technical support,  Dr. Haoyu Chen  from  Harvard Medical School  and  Alaina Shumate  from the  Johns Hopkins University School of Medicine  for insightful discussion. We thank  Jay Tracy  from  FGCZ  for reviewing the manuscript for English writing and clarity.
Funding This work was supported by the  Bill & Melinda Gates Foundation  ( INV-008213 ) and the  Functional Genomics Center Zurich (FGCZ). DP is funded by national funds through  FCT (Fundação para a Ciência e a Tecnologia , I. P. ) under the  Institutional Call to Scientific Employment Stimulus  (reference  CEECINST/00026/2018 ). WG is supported by a  Yushan Scholarship of the Ministry of Education in Taiwan.
Data availability Raw sequencing reads from PacBio (HiFi, CLR and Iso-Seq) and Illumina (Hi-C and shotgun) were deposited in the European Nucleotide Archive (ENA) database under the accession number PRJEB43673 (or ERP127652 as the secondary accession number in ENA). Assembled genome sequences of TME204 H1 and H2 were deposited in the NCBI database under the accession number PRJNA758616 and PRJNA758615, respectively. Assembled BAC clone sequences were deposited in the NCBI GenBank database under the accession numbers MZ959795, MZ959796, MZ959797, and MZ959798. The five supplementary files and the version of annotation files used in the current analysis were uploaded to the Mendeley database (http://dx. doi. org/10. 17632/fr6g4tgnfh. 1#folder-dbb00a94-9bc5-4dad-a2bc-8da65fe270a0).
Estimation of genome properties Estimation of genome complexities such as repeat content and the level of heterozygosity were made with k-mers in the Illumina PE reads using Preqc in SGA (v 0. 10. 15)  [57, 58]. Analyzed datasets and their accessions are: Human (ERR091571-ERR091574)  [58] , cassava AM560 (SRR2847385), Cassava TME204 (ERR5484652), cassava 60444 (ERR5484654)  (8) , cassava TME3 (ERR5484653)  (8).
PacBio CLR and HiFi whole genome assembly PacBio CLR reads were assembled using Falcon  [22]  in pb-assembly (v0. 06). PacBio HiFi reads were assembled using multiple HiFi specific assemblers, including Falcon in pb-assembly (v0. 0. 8), Improved Phased Assembler IPA (v1. 0. 5) (https://github. com/PacificBiosciences/pbipa), hifiasm.
We performed genome-wide association studies of seed weight and seed germination speed and homogeneity using 200 accessions from the M. truncatula HapMap collection via the FarmCPU algorithm. Post-GWAS analyses and RNA-seq data were used to refine our candidate gene lists related to different seed traits. A candidate gene, MtMIEL1, involved in the germination plasticity of seeds produced under heat stress was identified in M. truncatula and functionally validated in A. thaliana.
Genome-Wide Association Analysis Identification of single nucleotide polymorphisms (SNP) was obtained by whole-genome sequencing of the Medicago HapMap accessions selected in the M. truncatula HapMap project  (Stanton-Geddes et al. , 2013). Using the Medicago genome version 5 (Mtv5,  Pecrix et al. , 2018) , more than 4. 8 million SNP locations were identified and genotyped in the HapMap accessions. This 4. 8 million SNP genotypic dataset was used combined with the HapMap population structure (described in  Bonhomme et al. , 2014)  and the normalized phenotypic dataset regarding seed performances. In addition, the multi-locus model FarmCPU (Fixed and random model Circulating Probability Unification,  Liu et al. , 2016)  was used to perform association analyses described in  Chen et al. (2021a)  with a p-value threshold set to 1%.
Post-GWAS Analyses The PLINK algorithm  (Purcell et al. , 2007)  was used to identify correlated SNP and to correct for the linkage disequilibrium (LD) using the "clump" function. The following options of PLINK were used: "clump-kb 30" and "clump-r2 0. 7, " which represent the range of analyzed genomic region (± 30 kb) and the R-squared threshold (0. 7) to identify correlated SNP. In addition, enrichment analyses of Mapman functional classes of putative causal genes related to different seed performance traits were performed using the Clusterprofiler package  (Yu et al. , 2012)  using a hypergeometric test with Benjamini-Hochberg correction (q-values) and available in R. Mapman functional classes were obtained from Medicago annotated proteins using Mercator v. 4  (Schwacke et al. , 2019).
Transcriptomic Data The expression data of M. truncatula during seed development under optimal and heat stress conditions were obtained from  Chen et al. (2021b) , and raw data were stored on NCBI Gene Expression Omnibus (GEO; https://www. ncbi. nlm. nih. gov/geo/query/acc. cgi?acc=GSE160725). The differentially expressed genes (DEG) between optimal and heat stress conditions at the different seed developmental stages were identified using ImpulseDE2  (Fischer et al. , 2018)  for embryo and endosperm and DEseq2  (Love et al. , 2014)  for seed coat. DEG threshold was set as adjusted p-values below 5% following the Benjamini-Hochberg procedure to control the false discovery rate (FDR) described in  Chen et al. (2021b).
To reduce these gene lists and refine the identification of putative causal genes, we combined these datasets with gene annotations from Medicago Genome Version 5  (Pecrix et al. , 2018) , transcriptomic data related to expression specificity in M. truncatula seeds  (Chen et al. , 2021a) , and transcriptomic data during maturation of seeds developed both in optimal and heat stress conditions  (Chen et al. , 2021b ; Supplementary Table  5 ). In consequence, we highlighted some candidate genes related to seed weight such as MtrunA17_Chr8g0392741, encoding a phosphatidylethanolamine-binding protein, homologous to Arabidopsis MOTHER OF FT (At1g18100, MFT), which showed a highly significant association with WEIGHT_C (p = 8. 10 -20 ) and WEIGHT_H (p = 4. 10 -17 ) and a strong differential expression during M.
ACKNOWLEDGMENTS Seeds of different accessions used in this study were obtained from the  Medicago HapMap germplasm resource center  (http:// www. Medicagohapmap. org/hapmap/germplasm),and the  Genetic Improvement and Adaptation of Mediterranean  and tropical plants unit (AGAP,  INRA Montpellier ,  J. M. Prosperi ). We thank  Marie-Helene Wagner ,  Didier Demilly ,  Valérie Blouin , and  Jean Louis Queyreix  ( GEVES, Angers, France ) and the phenotyping platform  PHENOTIC Semences et Plantes (Phenome, Biogenouest ,  SFR 4207 QUASAV, Angers).
FUNDING This research was conducted in the framework of the regional program Objectif Végétal, Research,  Education and Innovation in Pays de la Loire , supported by the  French Region Pays de la Loire ,  Angers Loire Métropole , and the  European Regional Development Fund. This study was also supported by the  ANR  grant  REGULEG  (No. ANR-15-CE20-0001 ) and the  China Scholarship Council  ( CSC No. 201704910863 ) from the  Ministry of Education of P. R. China.
29 homogeneity T80T20_H 0. 17 0. 26 0. 17 -0. 01 0. 83 0. 75 0. 04 T80T20_PL 0. 02 0. 12 0. 16 -0. 34 0. 64 0. 79 -0. 47 0. 82 Geographical Longitude -0. 06 -0. 04 0. 05 -0. 11 0. 07 0. 14 -0. 11 0. 07 0. 11 location Latitude -0. 03 -0. 09 -0. 10 -0. 05 0. 03 0. 05 -0. 08 -0. 04 -0. 04 Altitude -0. 20 -0. 27 -0. 14 -0. 01 -0. 13 0. 01 0. 06 -0. 04 0. 04 Genome-Wide Association Analyses of Different Seed Traits in Response to Optimal and Heat Stress Conditions and Identification of Putative Causal Genes Finally, genome-wide association studies were performed on the nine transformed seed phenotypic data using the Fixed and random model Circulating Probability Unification algorithm (FarmCPU, Liu et al. , 2016) combined with the Medicago HapMap population structure as covariable and the Medicago HapMap SNP genotypic dataset (described in Bonhomme et al.
Methods. -MS patients were identified during a 6-year study period via the French national health data system (covering 97% of the general population) and characteristics of patients who received at least one treatment were compared to those that never received treatment over the indicated period. A state sequence analysis was performed to study in a longitudinal way MS patients who started DMTs in 2010 and then to classify them into groups of similar therapeutic patterns. DMTs were categorized into first-line, second-line and off-label use, and included untreated periods for at least six months. Groups that were obtained were described and compared using a multinomial logistic regression. Results. -A total of 112,415 patients with MS were identified, of whom 54. 0% received at least one DMT over the 6 years.