dataesr/scientific-paragraphs-categorization huggingface dataset:
For each parent, we selected the largest four regions conditioning on at most one block per chromosome (resulting block sizes from 150 to 215 kb; Figure  4 -figure supplement 7). Phylogenetic trees for each of the eight regions were then reconstructed based on polyploid genotypes of all 151 isolates and three outgroups (LmjFried, L. major, ENA: ERS001834; P283, L. tropica, ENA: ERS218438; LmexU1103 v1, L. mexicana, ENA: ERS003040; https://www. ebi. ac. uk/ena) using Nei's distances calculated with  StAMPP (v1. 5. 1, Pembleton et al. , 2013)  and the neighbour joining algorithm (R package ape, v5. 2) in R  (Supek et al. , 2011).
Copy number variation To identify large copy number variants (CNVs), realigned bam files for each sample were filtered for proper-pairs and PCR or optical duplicates were removed using samtools view (RRID:  SCR_002105, v1. 3, Li et al. , 2009). Coverage was then determined using bedtools genomecov (RRID:SCR_ 006646, v2. 17. 0) with parameters: '-d -split'  (Quinlan and Hall, 2010). Large duplications and deletion were identified using custom scripts in R (R Development Core Team, 2013): genome coverage was determined for 5 kb non-overlapping windows along the genome and each window was normalized by the haploid chromosome coverage of the respective chromosome and sample (i. e. median chromosome coverage divided by somy of the respective chromosome and sample). Large CNVs were identified through stretches of consecutive windows with a somy-normalized median coverage >= 0.
Measures of selection For all genes with annotated mRNAs in TriTrypDB (v38, RRID:SCR_007043;  Aslett et al. , 2010) , the longest open reading frames (ORF) were identified using a custom python script, resulting in 8234 genes with and five without ORFs. ORFs were then edited for SNP variation in both species using custom python scripts. Numbers of polymorphic differences within a species versus fixed differences to an outgroup of both, non-synonymous and synonymous sites, were annotated and tested for significance with Fisher's exact test using previously implemented software  (Holloway et al. , 2007). This was done for each gene and species always using the respective other species as an outgroup and removing sites polymorphic in the outgroup. An unbiased version of the a statistic  (Smith and Eyre-Walker, 2002; Stoletzki and Eyre-Walker, 2011) , intended to estimate the proportion of nonsynonymous substitutions fixed by positive selection across genes, was calculated with a custom R script.
Figure7. Two large CNVs that are shared between both species. (A) Chromosome 27 has a 25 kb long deletion that is present in 15% of all samples and four different groups. All chromosomes 27 that have this deletion in our dataset are diploid and the deletion results in a loss of this allele in the respective sample. (B) The duplication on chromosome 35 is 235 kb long and present in one isolate of group Ldon1 and Linf1, respectively. The insertion is once present on a disomic background with a 2-fold increase and once on a trisomic background with a 1-fold increase. The green rectangle marks the CD1/LD1 locus sequences for L. infantum described in Sunkin et al. (2001)  (Supplementary file 8). For A) and B) a few closely related samples not harbouring the respective CNV are also displayed and highlighted in dark grey.
Acknowledgements We are very grateful to  Gad Baneth  from the  Koret School of Veterinary Medicine, Hebrew University of Jerusalem , Israel;  Patrick Bastien  from the  Centre National de Reference des Leishmanioses Montpellier, France ;  Sayda Hassan El Safi  from  Khartoum University, Khartoum, Sudan ;  Olga Francino Martı  ´from  Universitat Auonoma de Barcelona, Spain ;  Marina Gramiccia  from the  Infectious Diseases Department Istituto Superiore di Sanita, Rome, Italy ;  Ketty Soteriadou  and  Evi Gouzelou  from the  Hellenic Pasteur Institute Athens, Greece ;  A. K. M. Shamsuzzaman  from  Mymensingh Medical College and Be-Nazir Ahmed from Institute of Epidemiology, Disease Control and Research, Bangladesh ;  Vanessa Yardley  from the  London School of Hygiene and Tropical Medicine  and  Peter Walden  from  ChariteUniversita ¨tsmedizin Berlin, Germany, each  for providing isolates for this study.
We also thank the Leishmania Collection of the  Oswaldo Cruz Foundation , Brazil and  Elisa Cupolillo  for providing the isolates MHOM/BR/2003/MAM, MHOM/BR/2007/ARL, MHOM/BR/2007/WC, voucher numbers:  IOC/L2651, IOC/L2935  and  IOC/L3015 , respectively. Further details of collaborators and their donated samples are given in Supplementary file 1. This project was supported by  Wellcome  through its core funding of the  Wellcome Sanger Institute  (grants  WT098051  and  WT206194 ) and by the  EU framework program   FP7-222895.
Data availability The 97 samples sequenced for this study are deposited in ENA under the study accession numbers: PRJEB2600 (ERP000767), PRJEB2724 (ERP000966), PRJEB8947 (ERP009989) and PRJEB2115 (ERP000169) (https://www. ebi. ac. uk/ena/data/view). All metadata on the 151 isolates including ENA accession numbers of individual samples are summarized in Supplementary file 1 (see also https:// microreact. org/project/_FWlYSTGf; Argimon et al. , 2016). Summary statistics and annotations from this study are available in Supplementary files 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13. Analysis.
6e, f ). In the Genotype-Tissue Expression (GTEx) RNA-seq dataset  31  from human tissue, C1QTNF1-AS1 was highly expressed in the adrenal gland and spleen, while linc00899 was broadly expressed in most of the tissues, with uterus being the highest (Supplementary Fig. 6g ). Linc0889 and C1QTNF1-AS1 facilitate timely mitotic progression. To characterise the mitotic phenotype further, we depleted linc00899 and C1QTNF1-AS1 in HeLa and HeLa Kyoto cells and examined the effect on mitotic progression with immunofluorescence and time-lapse microscopy imaging, respectively. Quantification of lncRNA-depleted cells using RNAi revealed an increase in the mitotic index compared to cells treated with control siRNA (Fig. 3a, b ). This was confirmed by time-lapse microscopy imaging of HeLa Kyoto cells where depletion of linc00899 and C1QTNF1-AS1 resulted in increased mitotic duration (Supplementary Fig.
g. mitotic/multinucleation index), μ represents the reference ratio and σ represents the standard deviation of ratios across wells. All the scripts used for the image analysis available at https://github. com/MarioniLab/LncScreen2018. High-content imaging screen: third-pass validation screen. The third-pass validation screen was performed in two replicates with four technical replicates using the top 25 candidates from each of the categories (mitotic progression, cytokinesis) using the same antibodies as in screen B. Correlation coefficients between replicate plates in third screen were calculated by Spearman's rank correlation (mitotic index = 0. 967888, viability = 0. 93249, multinucleation index = 0. 995897, cytokinetic bridges = 0. 898324). Single-molecule RNA FISH. Cells were grown on coverslips in 12-well plates, briefly washed with 1× PBS and fixed with PBS/3.
Images were captured using a Nikon TE-2000 inverted microscope with the NIS-elements software, a Plan Apochromat ×100 objective and an Andor Neo 5. 5 sCMOS camera. We acquired 25 optical slices at 0. 3-µm intervals. Images were projected in two dimensions using ImageJ and deconvolved with Huygens Professional. For validation of CHART-sequencing, Stellaris FISH Probes for intronic region of TPPP (Q670) were combined with linc00899 exonic probe (Q570) at a final concentration of 250 nM per probe set. To score whether TPPP (intronic signal) and linc00899 (exonic signal) colocalize, we only considered cells in which both signals were present. The sequences of RNA FISH probes are presented in Supplementary Data 4.
The proteins were then transferred to nitrocellulose membrane and blocked with 5% nonfat milk in TBS-T (50 mM Tris, 150 mM NaCl, 0. 1% Tween-20) for 1 h at RT. The membranes were incubated with primary antibodies in 5% milk in TBS-T with the following antibodies: TPPP/p25 (NBP2-34031, Novus, dilution 1:1000), β-tubulin (T019, Sigma, dilution 1:2000), p150 (610473, BD Transduction Laboratories, dilution 1:2000), Cyclin B1 (12231S, Cell signalling, dilution 1:1000), RAI14 (NBP1-94075, Novus, dilution 1:300), DNAAF5 (HPA020243, Atlas Antibodies, dilution 1:250), ITGB1BP1 (HPA071538, Atlas Antibodies, dilution 1:250), and phospho Histone H3 serine 10 (06-570, Millipore, dilution 1:1000). After overnight incubation at 4 °C, the membranes were washed with TBS-T and incubated with horseradish peroxidase secondary antibodies (GE Healthcare Life Sciences, 1:2000), and immunobands were detected with a Pierce ECL Western Blotting Substrate (Thermo Fischer Scientific, 32106).
Quantification of immunoblots normalised against appropriate loading controls was done using ImageJ. Uncropped scans of the immunoblots are provided in the Source Data file. The list of all primary and secondary antibodies is provided in Supplementary Table  4. Time-lapse microscopy imaging. HeLa (10,000 cells/well), HeLa Kyoto (10,000 cells/well), RPE1 (10,000 cells/well), MCF10A (15,000 cells/well) and HUVEC cells (15,000 cells/well) were cultured in 8-well chamber slides (Ibidi) with 200 μl/well of the corresponding medium. Imaging was performed in their corresponding medium. Time-lapse microscopy imaging was performed for all cell lines 48 h after transfection with RNAi or LNA gapmers. Mitotic duration was measured as the time from nuclear envelope breakdown until anaphase onset, based on visual inspection of the images.
Cytokinesis was measured from anaphase onset to abscission completion. Live-cell imaging was performed using a Zeiss Axio Observer Z1 microscope equipped with a PL APO 0. 95NA ×40 dry objective (Carl Zeiss Microscopy) fitted with a LED light source (Lumencor) and an Orca Flash 4. 0 camera (Hamamatsu). Four positions were placed per well and a z-stack was acquired at each position every 10 min (HeLa, HeLa Kyoto) or 5 min (MCF10A, HUVEC, RPE1) for a total duration of 12 h. To detect chromosome segregation errors (chromatin bridges and/or lagging chromatids), HeLa Kyoto cells were imaged every 4 min with only 2 positions/well. Voxel size was 0. 325 µm × 0. 325 µm × 2. 5 µm. Zen software (Zeiss) was used for data collection and analysis. Throughout the experiment, cells were maintained in a microscope stage incubator at 37 °C in a humidified atmosphere of 5% CO 2.
30. 0 with Ensembl GRCh38 version 91. Only alignments with mapping quality scores >10 and with the first read pair on the reverse strand were considered during counting. Approximately 80% of read pairs contained one read that was successfully mapped to the reference, and 74% of all read pairs in each library were assigned into exonic regions. Any outlier samples with very low depth (resulting from failed library preparation or sequencing) were removed prior to further analysis. The DE analysis was performed using the limma package v3. 36. 0  73. First, lowly expressed genes with average counts <3 were filtered out. Normalisation was performed using the trimmed mean of M-values (TMM) method to remove biases. Log-transformed expression values with combined precision/ array weights were computed with the voomWithQualityWeights function  74.
Pooled libraries were sequenced on a HiSeq4000 (Illumina) according to the manufacturer's instructions to generate paired-end 150 bp reads (CRUK CI Genomics Core Facility). CHART-seq was performed from five biological replicates using a mix of two sense control oligos for linc00899 as a negative control for the linc00899 pulldown. Reads were aligned to the hg38 build of the human genome using subread in paired-end genomic mode. A differential binding (DB) analysis was performed using csaw to identify lncRNA-binding sites in the pulldown compared to the sense control. Filtered windows were obtained as described for the CUT&RUN data analysis. Normalisation factors were computed by binning read pairs into 5-kbp intervals and applying the TMM method without weighting, to account for composition biases from greater enrichment in the antisense pulldown samples.
Coverage tracks were generated by computing the number of sequencing fragments per million overlapping each based, using library sizes adjusted according to the TMM normalisation factors for each library. Tracks were visualised using the Gviz package  84. Generation of C1QTNF1-AS1 CRISPR poly(A) site clones. Insertion of the transcriptional termination signal pAS  34  into the first exon of C1QTNF1-AS1 was performed a published CRISPR/CAS9 protocol  85. Briefly, the CRISPR pAS guide oligonucleotides were phosphorylated (T4 poly nucleotide kinase; NEB), annealed and ligated (Quick Ligase Kit, NEB) into BbsI (NEB) digested pX458 vector (Addgene, #48138). The oligonucleotides (Sigma-Aldrich, diluted in low TE EDTA buffer at 100 µM) used for the gRNA target sequence are listed in Supplementary Table  7.
PCR conditions for C1QTNF1-AS1-guide 70 were: 98 °C 30 s, 98 °C 30 s, 70 °C 30 s, 72 °C 30 s (repeat 30×), 72 °C 90 s, 4 °C forever. After PCR, 5 µl was used for BglII digestion (NEB, 2 h at 37 °C) and the products were loaded on a 2% agarose gel to confirm the pAS insertion (Supplementary Fig. 8a ). The rest of PCR reaction (15 µl) was also loaded on the gel as a control. Uncropped scan of the gel is provided in the Source Data file. The same genomic PCR product was also ligated into pJET1. 2/Blunt and transformed into bacteria (CloneJET; Thermo Fisher Scientific, K1231). To ensure representation by both alleles, plasmids were isolated and sequenced from a minimum of 5-10 bacterial colonies. This method revealed that C1QTNF1-AS1 pAS clones were homozygously targeted clones. Four clones were analysed (clone 95, 136, 153 and 169) by qPCR and live-cell imaging for the mitotic phenotype, along with the wild-type controls (clone 2 and clone 5) that were transfected with an empty vector PX458.
The second nested PCR used Nested Universal Primer A and C1QTNF1-AS1-5RACE-inner-2 = GATTACGCCAAGCT TGTCCTGATCTCCACCTGTCCCAAGC for the 5′ ends or C1QTNF1-AS1-3RACE-inner-2 = GATTACGCCAAGCTTGGAAACTTGGCAGACAGATCC AGCC for the 3′ ends. For linc00899, nine different 5′ sites and four different 3′ sites were identified. For C1QTNF1-AS1, six different 5′ sites and four different 3′ sites were identified. The fragments were purified after agarose gel electrophoresis with the QiaQuick Gel Extraction Kit (QIAGEN), cloned in pRACE vector as per the kit instructions and transformed into Stellar component cells (Clontech, 636763). The inserts were verified by Sanger sequencing. Uncropped images of RACE results are presented in the Source Data file. RACE results for linc00899. The most common starting site for linc00899 was CACGTCC, 87 bp upstream from the linc00899 TSS.
Expression of target genes in each fraction was analysed by qPCR. Data were normalised to the geometric mean of GAPDH and ACTB levels in each cellular compartment. U1 small nuclear RNA was used as a positive control for chromatin fraction. Coding potential assessment for lncRNAs. The Coding-Potential Calculator  88  (CPC; http://cpc. cbi. pku. edu. cn) and Coding Potential Assessment Tool 89 (CPAT; http://lilab. research. bcm. edu/cpat/index. php) were used to determine noncoding potential. LncRNAs with CPC scores >1 and CPAT scores >0. 364 were predicted to have protein-coding capacity. The PhyloCSF 90 score was taken from UCSC (https://github. com/mlin/PhyloCSF/wiki). Statistical analysis. The statistical significance of data was determined by twotailed Student's t test in all experiments using GraphPad Prism unless indicated otherwise.
Acknowledgements We thank all the members of Gergely and Odom groups for helpful discussions and  Julia Tischer  for critical reading of the manuscript. We also thank the  Genomics, Microscopy ,  FACS  and Research Instrumentation and Cell Service Core Facilities at the  CRUK Cambridge Institute. We thank  Keith Vance  ( University of Bath, UK ) and  Matthew Simon  ( Yale, USA ) for the help with the CHART-seq protocol,  John Rinn  ( University of Colorado ) for the lincXpress vector,  Steve Henikoff  ( Fred Hutchinson Cancer Research Center, USA ) for providing the reagents for CUT&RUN and  Irene Cantone (University Federico II of Naples)  for assistance with the DNA FISH. This work was made possible by funding from  Cancer Research UK  ( C14303/A17197  to D. T. O. , F. G. , and J. C. M. ,  A24455  to F.
Data availability A reporting summary for this article is available as a Supplementary Information file. Sequencing data are available in the ArrayExpress database (http://www. ebi. ac. uk/ arrayexpress) with the accession codes E-MTAB-7432 (RNA-seq), E-MTAB-7418 (CHART-seq) and E-MTAB-7419 (CUT&RUN). The imaging data have been submitted to the Image Data Resource (https://idr. openmicroscopy. org) under IDR accession number idr0056. The source data underlying Figs. 2b, d ; 3a-c, e-g; 4e-i; 5c, e; 6a, i; 7a-f; 8a-c; and 9b and Supplementary Figs. 3a, b; 4a, b; 5a, b; 6a, c, e, f; 7a, d; 8a, c, d ; 9a-c; 10a-e; and 14a, b are provided as a Source Data file. All data are available from the corresponding authors upon reasonable request.
The Taurus-Littrow valley on the Moon was the location of intensive geologic fieldwork during three days in December 1972. In situ activities at sampling stations were systematically documented by the astronauts using a series of overlapping images taken with their Hasselblad cameras. We investigated how this Apollo image archive can be used to perform 3-D reconstructions of several boulders of interest using close-range photogrammetry. We specifically focused on seven different boulders located at Stations 2, 6, and 7, at the foot of South and North Massifs, respectively. These boulders represent samples from highland materials, which rolled down the slopes of the surrounding hills. We used the Agisoft Metashape software to compute 3-D reconstructions of these boulders, using 173 scanned images as input.
The location of these three sites is shown in Figure  1a  on the traverse map produced from  [15] , building on the initial work of  [16] , together with panoramas taken in situ near the three areas of boulders. The topic of this paper is to describe the reconstruction process of the main boulders, from the input data up to the visualization of the products. The results of the 3-D reconstructions of the boulders are shared through a public web-based platform. The Apollo 17 crew spent three days at the Taurus-Littrow site in December 1972. The southernmost part of the traverse was reached during the second extra vehicular activity (EVA), at Station 2 located at the foot of South Massif (Figure  1a, b ). During the third EVA, the sampling sites Station 6 and Station 7 were selected as a suitable location to collect possible ancient highland material from the North Massif (Figure  1c, d ).
Context Orbital Imagery We first used the available orbital imagery to map the Taurus-Littrow valley using the ArcGIS Geographic Information System. The purpose was to give a broader regional context of the sampling sites once integrated into virtual reality, and to precisely locate the sites of interest. The general context was computed using a subset of the SELenological and Engineering Explorer (SELENE) "Kaguya" Terrain Camera (TC) global orthomosaic at 4096 pixels per degrees  [17] , available on the United States Geological Survey (USGS) astrogeology science center website. With a resolution of ~10 m per pixel, this data set bridges the gap between Clementine and the LROC WAC (~100 m/pixel) and the LRO NAC (~1 m/pixel) and therefore provides relevant contextual information. The Kaguya-TC mosaic was draped over a digital elevation model produced from the merging of LRO Lunar Orbiter Laser Altimeter (LOLA) data and SELENE Kaguya TC data, available at a horizontal resolution of 512 pixels per degree (corresponding to ~59 m per pixel at the equator) and a typical.
Context Orbital Imagery We first used the available orbital imagery to map the Taurus-Littrow valley using the ArcGIS Geographic Information System. The purpose was to give a broader regional context of the sampling sites once integrated into virtual reality, and to precisely locate the sites of interest. The general context was computed using a subset of the SELenological and Engineering Explorer (SELENE) "Kaguya" Terrain Camera (TC) global orthomosaic at 4096 pixels per degrees  [17] , available on the United States Geological Survey (USGS) astrogeology science center website. With a resolution of ~10 m per pixel, this data set bridges the gap between Clementine and the LROC WAC (~100 m/pixel) and the LRO NAC (~1 m/pixel) and therefore provides relevant contextual information. The Kaguya-TC mosaic was draped over a digital elevation model produced from the merging of LRO Lunar Orbiter Laser Altimeter (LOLA) data and SELENE Kaguya TC data, available at a horizontal resolution of 512 pixels per degree (corresponding to ~59 m per pixel at the equator) and a typical vertical accuracy ~3 to 4 m  [17, 18].
The Hasselblad Surface Image Data Set During their EVAs, the astronauts used two Hasselblad 500 EL data cameras attached to the chest of their spacesuits. Cameras were calibrated and equipped with a reseau plate in front of the image plane to provide a photogrammetric reference  [21]. The grid consists in 5 × 5 mm crosses at 10mm intervals, imaged in each frame of the 70-mm film. The cameras were fitted with a Zeiss Biogon lens with a 60-mm focal length, thus providing a moderately wide field of view. The astronauts systematically acquired single frames, full panoramas, overlapping images, and stereo pairs along their traverse path and at sampling stations to document the samples' collection and allow post-flight geological analysis  [22]. We mainly used two different online resources to compile the relevant imagery database for our research project.
The Hasselblad Surface Image Data Set During their EVAs, the astronauts used two Hasselblad 500 EL data cameras attached to the chest of their spacesuits. Cameras were calibrated and equipped with a reseau plate in front of the image plane to provide a photogrammetric reference  [21]. The grid consists in 5 × 5 mm crosses at 10-mm intervals, imaged in each frame of the 70-mm film. The cameras were fitted with a Zeiss Biogon lens with a 60-mm focal length, thus providing a moderately wide field of view. The astronauts systematically acquired single frames, full panoramas, overlapping images, and stereo pairs along their traverse path and at sampling stations to document the samples' collection and allow post-flight geological analysis  [22]. We mainly used two different online resources to compile the relevant imagery database for our research project.
Several commercial or freeware software can be used to perform all the processing steps. An example of photogrammetric reconstruction made with the iWitness ProTM 3. 6 software  [25]  on a series of six overlapping images of the 70019 sample area is shown in  [8]. Another example of photogrammetric reconstruction is presented in  [26] , using Agisoft PhotoScan Professional (recently renamed "Metashape") on descent images of the Apollo 15 landing site. In this work, we also relied on Agisoft Metashape (v. 1. 6. 2, [27] ), which is one of the most widely used SfM solutions in the field of planetary science for geological applications (e. g. ,  [3, [5] [6] [7] 11, 12] ).