dataesr/scientific-paragraphs-categorization huggingface dataset:
Acknowledgments. We express our gratitude to the entire  IMGT® team  for their ongoing dedication and unwavering enthusiasm. IMGT® is currently supported by the  Centre National de la Recherche Scientifique (CNRS)  and the  University of Montpellier. IMGT® is member of the  French Infrastructure "Institut Français de Bioinformatique ", IFB as well as member of BioCampus, MAbImprove and IBiSA. AK was co-funded by " Direction de la Recherche, du Transfert Technologique et de l'Enseignement Supérieur" of Occitanie Region  under the  N°20007399 / ALDOCT-001023  contract as well as IMGT® proper resources. This work was granted access to the  High Performance Computing (HPC)  resources of Meso@LR and of " Centre Informatique National de l'Enseignement Supérieur" (CINES).
Code availability. Once this paper is accepted, the implementation code and trained models will be available at (https://github. com/anjanakushwaha/RobustpM HC). PyTorch 1. 10. 0 and CUDA 11. 7 was used to calculate performance metrics. Pandas v. 2. 1. 1 and Numpy v. 1. 22. 3 were used for data processing. Matplotlib v. 3. 5. 1 were used to generate figures. Data availability. Once this paper is accepted, the data will be available at (https://github. com/anjanakushwaha/RobustpMH C/tree/main/dataset). It contains the training data, independent test data, external test data, anthem dataset, neoantigen dataset, HPV dataset, COVID dataset, crystalIMGT dataset and neoepitope dataset.
ChIP-seq analysis The ChIP-seq libraries were sequenced on an Illumina Hiseq 4000 sequencer as pairedend 100 bases by the GenomEast platform, a member of the 'France Genomique' consortium (ANR-10-INBS-0009). ChIP samples were purified with Agencourt AMPure XP beads (Beckman Coulter) and their concentration was quantified with Qubit (Invitrogen). For the preparation of the ChIP-seq libraries, a total of 10 ng of dsDNA was purified using the MicroPlex Library Preparation kit v3 (C05010001, Diagenode s. a. , Seraing, Belgium), according to manufacturer's instructions. RTA and bcl2fastq were performed using base calling and image analysis. Mapping of sequence reads to the reference genome (mm10) was performed with Bowtie 2  58  , using the parameters: -q -N 1 -X 1000. Bedtools was used for the removal of reads overlapping with ENCODE hg38 blacklisted region V2  59.
4a ). WT cells isolated from CT mosaics were annotated as WT, and those from CCM2 mutant mosaics as WT-CCM2. The dataset was equally distributed between WT (32%), WT-CCM2 (32%) and siCCM2 (36%) conditions (Fig. 4b ). However, a clear segregation was observed between siCCM2 clusters and both the WT/WT-CCM2 clusters confirming the evident effect of CCM2 silencing on the transcriptomic profile of the mutant ECs (Fig. 4b ). Graph-based clustering of the 1434 ECs retained for analysis identified seven clusters based on upregulated genes associated with biological functions related to proliferation, senescence, and angiogenesis (clusters angiogenesis1/2/3) as well as two additional clusters with genes related to vasculature remodeling and RNA splicing (Fig. 4c , Supplementary file 1). The WT and WT-CCM2 conditions largely comprised proliferative, blood vessel remodeling and angiogenesis regulating cells, whereas loss of CCM2 prompted migration and sprouting angiogenesis activity, as well as non-proliferative G1 arrest, consistent with our prior discovery of SASP in CCM  24, 41.
Acknowledgements. We thank the members of the  Van Oosterwyck laboratory  for thoughtful feedback;  Transcriptom Core Facility  of the  Institute in Regenerative Medicine and Biotherapy ,  CHU-INSERM-UM Montpellier , https://irmbmontpellier. fr/ for the single-cell RNA Sequencing processing; and the  MicroCell microscopy facility  at IAB,  R. Nuyts  and  A. Grichine  for support with microscopy. These studies were supported by  Research Foundation Flanders (FWO)  PhD fellowship  1S68820N , postdoctoral fellowship  1259223N , projects  G087018N ,  G0C2422N ; infrastructure grant  I009718N ,  KU Leuven  grants  IDN/19/031 ,  iBOF/21/083 C ;  ERANET NEURON   JTC 2022  call -project  G0L1522N , Project.
Querying the STRING database with all identified targets showed a close physical or functional interaction for most (Figure  4B )  (26). 5 detected hits function as GSK3-ß inhibitors and 4 hits as ROCK1/2 inhibitors. A number of target annotations occurred only once and were not connected to other annotated targets. Often those were related to neuronal signaling or remodeling such as acetylcholinesterase (AChE) inhibition, dopamine D2 receptor (DRD2) or histamine H1 receptor (HRH1) antagonism or actin-related protein 2/3 complex subunit 2 (ARPC2) inhibition. Next, we performed dose-response testing using all 42 identified hit candidates. We used the same CRISPR-engineered SHANK3-deficient cell line HT3 as before and additionally the isogenic control cell line WT2 expressing SHANK3 from both alleles to identify SHANK3 deficiency-specific molecules.
3 standard deviation (SD) window around the DMSO control's Ki67 and HuC/D ratio means. Molecules that increased proliferation and decreased differentiation and did not lower the nuclei count < 2,000/well were considered as hit candidates. The primary screen was performed in duplicate and all data is shown. (B) Visualization of known physical and functional interactions of all protein targets attributed to the detected hit candidates annotated in the STRING biological database. The color coding represents the frequency of target annotations in the hit list. Compounds can have multiple targets (see also Table  S3 ). (C) Representative images of CRISPR-engineered SHANK3+/-and control SHANK3+/+ NPCs treated with Benproperine at multiple doses. (D) Dose-response effects of 11 compounds on the ratio of proliferating Ki67 positive SHANK3+/-and control SHANK3+/+ NPCs.
Image segmentation and feature extraction was performed with our in-house software PhenoLink (https://github. com/Ksilink/PhenoLink). Image segmentation was performed on illumination corrected raw images based on fluorescent channel intensity thresholds empirically determined per plate. Nuclei were segmented using intensity and size thresholds allowing the identification and counting of debris, dead cells and live cells. The ratio of HuC/D and Ki67 positive cells was calculated based on an intensity threshold for segmentation and a second colocalization threshold with the segmented nuclei (50% and 5%, respectively). Synapses were identified in a three step process: First a MAP2-channel based neurite skeleton was determined. Secondly, puncta fitting based on local maxima and individual puncta intensity profile were used to identify puncta in the Synpasin1 and SHANK3 channels.
Compounds that lowered the live cell count below 2,000 per well were discarded as toxic. All raw data and the corresponding analysis workflow is available as a Jupyter notebook on GitHub (https://github. com/Ksilink/Notebooks/tree/main/Neuro/SHANK3screening). Potential biological interactions between annotated hit targets were explored and visualized using the STRING biological database. All available annotated target-related gene name inputs of all 42 primary hits are summarized in Table  S3.
METE is also present in many METH-containing eukaryotic algae, which renders them facultative B 12 users  (31). The most parsimonious explanation is an ancestral presence of both METE and METH in eukaryotes with obligately B 12dependent species having lost METE, and plants, fungi, and other species that do not have B 12 -associated metabolism having lost METH. In the last five years, the dramatic expansion in plant and algal sequence resources, such as through the OneKp project (3), a global initiative to sequence 1,293 publically available transcriptomes from across the plants, and close (particularly freshwater) algal relatives in the Viridiplantae  (33) , has provided unprecedented insights into early plant evolution. This dataset has provided particular insight into the phylogenetic relationships of plants, including the probable monophyly of bryophytes (mosses, liverworts, and hornworts) within the plants  (3).
Distribution of encoded METH/ METE proteins indicate B 12 presence in hornworts We identified homologues of the thirteen B 12 -associated proteins using available information from from algal (Chlamydomonas reinhardtii, Euglena gracilis, Phaeodactylum tricornutum) and human genome sequences (Dataset S1, sheet 1). These were used to search a composite genome and transcriptome library of photosynthetic eukaryotes (Dataset S1, sheet 2). The library contained: 53 algal and plant genomes, including those of the hornworts Anthoceros agrestis and A. punctigera  (6) ; decontaminated versions of the 1,000 plant transcriptomes (OneKp ; 1,293 libraries)  (3, 33)  and the F o r R e v i e w O n l y Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP; 305 libraries)  (36) ; and 32 further eukaryotic transcriptomes, as described previously  (37).
Certain libraries were represented in more than one library type (e. g. , genome plus MMETSP; genome plus OneKp) with 1,666 unique strains in the final dataset. Homologues were retrieved by reciprocal BLAST best-hit (RbH), and further evaluated by single-gene RAxML trees, and PFAM domain analysis, and were categorised taxonomically following recently published multigene phylogenies of plant and algal diversity  (3, 37). Full outputs are provided in Dataset S1, sheets 3-4. The evolutionary distributions of each protein are shown schematically in Fig. 2. The patterns underline the widespread occurrence of the B 12 -dependent form of methionine synthase, METH, across eukaryotic algae, found in all major marine groups, and in streptophyte relatives of land plants  (3). METH, alongside METE, was further detected in multiple distantly related hornwort genera, suggesting widespread conservation of B 12 -dependent methionine synthases across the class Anthoceratophyta (Dataset S1, sheet 5)  (3, 5).
The METH phylogeny robustly placed the hornwort sequences with other streptophyte sequences (RAxML bootstrap support : 100%), and as a sister-group to the charophytes / coleochaetales (Fig. S1  ; Dataset S1). This group was positioned more deeply within Viridiplantae, as a sister to the chlorophytes (RAxML bootstrap support: 100%; Fig. S1 ). Each of the Megaceros, Nothoceros, Phaeoceros and Paraphymatoceros sequences possessed all five PFAMs associated with METH (homocysteine S-methyltransferase, PF02574 ; pterin-binding, PF00809 ; B 12 -binding, PF02607 and PF02310 ; and the activation domain, PF02965) with similar e-values to functionally characterised equivalents from algae (Fig. S2 )  (39). The three identified Anthoceros homologues (A. agrestis Bonn : 228_5027_1_ A. agrestis Oxford utg000003l_252_1; A.
punctigera, _utg000098l_165_1) possessed all PFAMs apart from the first B 12 -binding (PF02607) domain. However, this PFAM is detected in alternative gene models in each genome (A. agrestis Bonn: 362_443; A. agrestis Oxford: utg000003l_664; A. punctigera, utg000145l_284). We note that at the very least the A. agrestis Oxford N-and C-terminal models are encoded on the same chromosomal element (utg000003l), suggesting that Anthoceros also possesses an active METH. The hornwort sequences all had conserved active sites (e. g. , the substrate-binding pocket of the pterin-binding site) associated with METH activity (Fig. S2 )  (39). We also considered the distribution of the methionine synthase reductase (MTRR) necessary for METH activity. Well-conserved homologues were detected across hornwort genomes and transcriptomes, but were absent from other plant groups (Fig.
Widespread occurrence of two distinct METE isoforms in plants All plant libraries studied possessed METE sequences, including hornworts, indicating that both genes were present in the last common plant ancestor (Fig. 2 ). The hornwort METE resolved with other plant homologues (Fig. S1 ) and possessed well-conserved N-terminal (PF08267) and C-terminal catalytic (PF01717) PFAM domains (Fig. S2 ), indicating a vertical origin and possible functionality. The plant METE enzymes resolved phylogenetically in two discrete families: a conventional isoform with 1,768 recovered examples (labelled "Clade 1"); and a less frequently observed isoform ("Clade II") with 125 observed examples (Fig. S1  ; Dataset S1). Both isoforms contained both PFAM domains, i. e. are likely to function as methionine synthases (Fig.
S2  ; Dataset S1). In certain cases, Clade I and II were found in the same organism (e. g. , the hornworts Megaceros vincentianus and Phaeoceros carolinianus). Both Clade I and Clade II isoforms were detected in vascular plant, moss, liverwort, hornwort and streptophyte sequences (Fig. S1 ), suggesting their presence in the last plant common ancestor. All three characterised Arabidopsis methionine synthases (At5g17920; At3g03780; At5g20980) resolved within Clade 1, but the Clade II enzymes all showed greater proximity by BLASTp analysis to these than to Arabidopsis adenosyl-methionine synthases (At1g02500; At4g01850; At3g17390; At2g36880) (Dataset S1, sheet 6)  (40). Both Clade I and Clade II isoforms were distantly positioned to chlorophyte METE sequences, which formed a sister-group to red algae, cryptomonads and chromerids (Fig.
Distribution of METE sequences confirms widespread B 12 auxotrophy in algae METE was absent from many of the algal libraries searched (Fig. 2 ). Transcriptome libraries may under-report the presence of METE, as it may be transcriptionally repressed in B 12 -supplemented cultures  (32) , and therefore we limit our consideration to lineages with at least one sequenced genome. Consistent with previous studies  (41) , the METH and METE distributions project B 12 auxotrophy in haptophytes (including three genomes included: Emiliania huxleyi, Chrysochromulina tobinii, and Pavlovales sp. CCMP2436). Only one potential haptophyte METE homologue (from Pavlova lutheri UTEX LB1293) was found by RbH, but was excluded as a probable green algal contaminant (Dataset S1,  Sheet 21). We note of a recently discovered and alternative METE-related proteins in the haptophyte Phaeocystis, discussed below  (42).
Finally, dinoflagellates (including three genomes from Symbiodinium sp. ) were found to possess only partial METE sequences, which lacked the conventional N-terminal PFAM domain (MetH_synt_1; PF08267), following previous studies (39) (Dataset S1). We did, however, identify complete METE sequences containing both PFAM domains in the chromerids Chromera velia and Vitrella brassicaformis, which are the closest photosynthetic relatives of dinoflagellates  (47). The dinoflagellate METE-like sequences were distantly related to other algae and instead resolved with Archaea (Fig. S1 ), which likewise lacked the N-terminal PFAM domain. This may suggest a horizontal acquisition of the dinoflagellate METE-like gene accompanied by the loss of the complete METE isoform. Finally, the METE sequences of the red algae Porphyridium and Cyanidioschyzon and the chrysophyte Poteriospumella resolved with bacterial homologues (Dataset S1 ; Fig.
MCM and RNR II enzymes are restricted to individual algal lineages Next, we considered the distributions of B 12 -dependent MCM and RNR II across our dataset (Fig. 2 ). Neither enzyme was detected in streptophytes (including hornworts), and were absent from chlorophytes, except for sporadic occurrences that are likely consistent with horizontal acquisitions (discussed below). MCM homologues were primarily detected in algae with secondary red chloroplasts (e. g. , diatoms, cryptomonads, haptophytes, ochrophytes), typically possessing well-conserved PFAM domains, and predictable mitochondrial-targeting sequences (Dataset S1; Fig. S3 ). MCM is implicated in the catabolism of branched-chain amino acids in diatoms under nitrate exhaustion, but lacks an apparent RNAi mutant phenotype  (48) , so its significance for B 12 dependence in eukaryotic algae remains to be determined.
Similarly, Geminigera cryophila, which is the only cryptomonad within our dataset to lack METH and encode METE, was collected from the Antarctic, which is characterised by vitamin B 12 -limitation (Fig. 1 )  (29). Lastly, many of the B 12 -independent algal species are symbionts of other organisms (Leptosira obovata and Trentepohliales, from lichens (54); Vitrella brassicaformis, from coral (47); and Brandtodinium nutriculum, a foraminiferan symbiont (55)), and may be subject to B 12 limitation, or even potentially receive methionine and as folate from their hosts.
Discussion We have queried the distribution of thirteen B 12 -associated proteins across more than 1,600 plant and algal genomes and transcriptomes, in particular profiting from sequence data from the OneKp transcriptome project (3) (Fig. 1 , Dataset S1, sheet 2). Our data suggest the hitherto undocumented retention of vertically inherited B 12 -associated methionine synthesis pathways (METH, MTRR) and B 12 uptake-associated proteins (CblB, C D, J) in hornworts, and the retention of potential CblB and CblJ homologues in liverworts (Fig. 2 ). Formally, the active use of B 12 by hornworts awaits functional characterisation, e. g. by bioassay of B 12 content (56), from experimental inference of B 12 use such as B 12 -dependent suppression of hornwort METE  (32) , or via uptake of fluorescently-labelled B 12 analogues (57) by hornwort cells.
Materials and Methods Homologue detection : Potential homologues of thirteen Vitamin B 12 -associated enzymes (listed in Dataset S1, sheet 1) (31) were searched across a composite library of 1,663 non-redundant plant and algal genomes and transcriptomes (Dataset S1, sheets 2-4)  (3, 36, 37)  by BLASTp with threshold e-value 10 -05. Potential matching sequences were extracted and searched by BLASTp against the complete Arabidopsis thaliana genome  (63) , which uniquely encodes METE, supplemented with the query sequences defined above. Sequences that retrieved a best-scoring match to a query sequence were retained for downstream phylogenetic analysis (Dataset S1, sheets 5-17). For METE which is retained in plants, sequences that retrieved one of the three Arabidopsis methionine synthases were likewise retained for downstream analysis  (40).
The best-scoring tree was inspected for branches of contaminant origin (e. g. sequences from one algal library only that resolved with bacterial homologues). Homologues that passed the initial RAxML curation were passed through a second iteration of mafft alignment, manual curation, and RaxML phylogeny, prior to enumeration of homologue presence/ absence (Dataset S1, sheets 18-21). Functional, targeting and biogeographical annotation : PFAM domains were searched in each homologue retrieved by the initial RbH search by HMMER v 3. 3. 2 against the Pfam v 35. 0 library  (68). Sequences that retrieved PFAM domains associated with each query protein with threshold e-value 10 -05 were recorded (Dataset S1, sheet 22). For CbA1, where no PFAM is associated with the Chlamydomonas reinhardtii sequence, a specific hmm was generated from the characterised Phaeodactylum and Chlamydomonas proteins and used to screen homologues (Dataset S1, sheet 23).
Localisations for each protein were inferred following previous studies  (37) , considering the consensus predictions of WolfPSort, SignalP, ASAFind, TargetP and HECTAR (Dataset S1, sheet 23). Collection sites were recorded for each algal species using the corresponding culture collection records considering strain synonyms, and where appropriate direct information from the literature or collector  (69) (70) (71). Data deposition : An interactive map of all algal collection sites identified within the dataset, shadeable either via phylogenetic affiliation or inferred Vitamin B 12 metabolic status, is available via https://tinyurl. com/3esfpkmv. 25 ) and  (31). NB that many of these proteins have been established from human cellular models, and further functional diversity in B 12 metabolism may exist in nonmodel species.
Acknowledgments Funding information : RGD acknowledges an  ERC Starting Grant  ( « ChloroMosaic »  ; grant number  101039760 ), awarded  2023-2027. Work at the IBENS is supported by the  Investissements d'Avenir programmes PSL  and  MEMOLIFE :  MEMO LIFE  ( ANR-10-LABX-54 ), and  PSL*Research University  ( ANR-11-IDEX-0001-02 ).
Acknowledgments : The authors thank  Dr. Fabio Rocha Jimenez Vieira  ( IBENS ) for assistance with the decontamination of the OneKp transcriptome dataset; and  Ms. Cathy Johnston  ( CSIRO ),  Dr. Maike Lorenz  ( Georg-August-Universität Göttingen ),  Prof. Michael Melkonian  ( Universität Köln ) and  Mr. Stephen Peña  ( UTEX Culture Collection ) for the assistance of strain isolation sites tabulated in Dataset S1.
The light scattered by the nano-objects appears as individual spots which trajectories are recorded by a CCD camera, operating at 30 frames per second, through a microscope. For each sample (with or without SPION), measurements were achieved a few minutes after mixing. Each measurement consists of 3 acquisitions of 30 s, at 25 • C. The size of each object was then individually deduced from the analysis of its Brownian motion (NANOSIGHT NTA 2. 0 Analytical Software) using the viscosity of the appropriate solvent, i. e. 0. 9 10 -3 Pa. s for water or 1. 55 10 -3 Pa. s for the THF/water (23/77 w/w) mixture  (Mahendra et al. , 1994). Electrophoretic mobility. Electrophoretic mobility was measured using a Malvern Nanosizer operating at 633 nm and equipped with a dip cell (ZEN1002). The reported values represent the mean and standard deviation of three independent sets of 100 measurements.
2 , because they are beyond the detection limit of conventional analytical methods, such as HPLC, and values found in some databases seemed questionable  (Wang, 2011). Paclitaxel is a mitotic inhibitor for the treatment of advanced carcinoma of the ovary, and other cancers such as breast and lung cancers  (Li, 2011). The α-tocopherol, known as "vitamin E", is an antioxidant used as a dietary supplement. Based on our previous studies, we hypothesized that due to their low water solubility (typically below 10 -5 mol. L -1 ) these molecules may be precipitated to form the core of the capsules. We used superparamagnetic iron oxide nanoparticles (SPION) as the shell material. These SPION (4. 8 (+/-0. 9) nm nanocrystals, coated with alkyl chains) were synthesized via the hydrolysis of [Fe(N(SiMe 3 ) 2 ) 2 ] in a mixture of octylamine and oleic acid in the absence of any additional solvent  (Goubault, 2021).
Acknowledgement The authors wish to thank  L. Rault  ( Themis ) and  A. Burel  and  A. Dupont  ( MRic TEM, UAR Biosit ) for transmission electron microscopy analysis. The authors also thank  H. Solhi  ( ImPACcell, UAR Biosit ) for the cytotoxocity studies. This work was supported by the  University of Rennes , the  Centre National de la Recherche Scientifique (CNRS)  and the  ANR. We also acknowledge financial support from  ITMO Cancer of Aviesan  within the framework of the  2021-2030 Cancer Control Strategy , on funds administered by  Inserm.
GO-BP provides a descriptive genomic annotation which might is not suitable to elucidate slight functional differentiations between species. However, the impediment is that there is not any controlled vocabulary which describes the universe of cellular functionality in the level of pathways' topology for a plethora of species. For instance, the BioCyc database  (Karp et al. , 2019)  contains curated and computationally inferred annotation for thousands of species only for metabolic pathways, while Reactome Pathways  (Jassal et al. , 2020)  provides curated annotation for the network of pathways of a few model-species. A way to solve this issue could be the massive integration of data from different vocabularies into a unified ontological schema. In addition, the weaker segregating capacity of the PN in the two Prokaryotic kingdoms might also indicates that their evolutionary pressure was managed through the functional diversification of selected genes (e.