Resultados de investigación

Contains 2 files, 1 .xls ; 1 .pdf : Allele sizes in base pairs obtained from 26 microsatellites analyzed in the 174 Vitis vinifera L. genotypes studied (three columns with the identification as Genotype number, Genotype code and population), and 52 columns with two allele sizes from 26 SSRs. Under a Creative Commons License Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)., [EN] This dataset includes the SSR-based molecular profiles of 174 grapevine (Vitis vinifera L.) genotypes used to study the genetic diversity and structure in a Spanish Grape Germplasm collection. These profiles derived of the study carried out with 26 SSR markers to characterize 411 accessions preserved at the Aragon grapevine Germplasm Bank Collection in (BGVA). From the 156 non-duplicate accessions curated at the Aragon Germplasm Bank, we kept 113 representative genotypes (47 Spanish known, 51 Spanish unknowns, and 15 from European-oriental origin), and we added 61 representative genotypes curated at the El Encin Germplasm Bank to stablish a comparative study. The dataset was mainly generated within the project RF2012-00027-C05-02 ("Documentation, characterization, and rationalization of grapevine germplasm prospected and conserved in Spain. Creation of a nuclear collection")., [ES] Esta base de datos incluye los perfiles moleculares obtenidos con marcadores microsatélites (SSR) en 174 genotipos de vid (Vitis vinifera L.) utilizados para determinar la diversidad genética y estructura poblacional de una colección española de germoplasma. Estos perfiles derivan de 26 SSRs utilizados para caracterizar 411 accesiones conservadas en el Banco de germoplasma de vid de Aragón (BGVA). De las 156 accesiones no-duplicadas mantenidas en el BGVA, se eligieron 113 genotipos representativos (47 españoles conocidos, 51 españoles no conocidos, y 15 de diverso origen europeo u oriental), y se añadieron otros 61 genotipos representativos mantenidos en el Banco de Germoplasma de El Encin con el fin de establecer un estudio comparativo. Los datos se generaron mayormente en el marco del proyecto RF2012-00027-C05-02 ("Documentación, caracterización, y racionalización del germoplasma de vid prospectado y conservado en España. Creación de una colección nuclear")., Grants RF2012-00027-C05-02 and RTA2014-00083-C03 funded by Spanish Institute for Agricultural and Food Research and Technology (INIA), which were co-financed with FEDER funds. Grants A44, A09_20R and A09_23R funded by Regional Government of Aragón; Erasmus plus fellowship P BRAGANT 01 supported by the Instituto Politécnico de Bragança, Portugal, which all were co- funded with FEDER funds., No

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cancers14030670/s1, Figure S1. Sanger sequencing results of the CYBA (upper panel) and TRPM4 (lower panel) wild type and mutant sequences; Figure S2. Splicing functional assays of TRPM4 variant c.25-1G>T. (A) Fluorescent fragment analysis by capillary electrophoresis of RT-PCR products generated by the wild type and mutant minigenes. The canonical and the aberrant ∆(E2p2) transcripts are shown as blue and red peaks, respectively, while the LIZ500 size standard is displayed as orange peaks. (B) Schematic representation of the canonical (above) and anomalous (below) transcripts. Variant c.25-1G>T is shown in red; acceptor sites are underlined; splicing events are shown as broken arrows; Figure S3. SiRNA knockdown of CYBA or TRPM4 lead to reduced mRNA and protein of the respective genes: mRNA (A) and protein (B) levels of CYBA and TRPM4 decreased after siRNA knockdown of CYBA or TRPM4 in LS174T cells; mRNA (C) and protein (D) levels of CYBA and TRPM4, decreased after siRNA knockdown of CYBA or TRPM4 in HT-29 cells. For real-time PCR assays, three independent experiments in triplicate were performed and means and standard errors of the means are presented on the graphs. For western blot two independent experiments were performed;Table S1. Summary of the sequencing coverage and quality statistics for each sample; Table S2. Loss-of-function variants segregated with the disease in 15 colorectal cancer families., Peer reviewed

The following are available online, spectral and analytical data for hybrid compounds.. NMR spectroscopic and mass-spectrometric data NMR and Mass Spectra: Figure S1: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 3 Figure S2: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 3 Figure S3: HRESI-MS Spectrum of Compound 3 Figure S4: ESI-MS Spectrum of Compound 3 Figure S5: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6a Figure S6: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6a Figure S7: HRESI-MS Spectrum of Compound 6a Figure S8: ESI-MS Spectrum of Compound 6a Figure S9: 1H -NMR (500 MHz, CDCl3) Spectrum of Compound 6b Figure S10: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6b Figure S11: HRESI-MS Spectrum of Compound 6b Figure S12: ESI-MS Spectrum of Compound 6b Figure S13: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6c Figure S14: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6c Figure S15: HRESI-MS Spectrum of Compound 6c Figure S16: ESI-MS Spectrum of Compound 6c 2 Figure S17: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6d Figure S18: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6d Figure S19: HRESI-MS Spectrum of Compound 6d Figure S20: ESI-MS Spectrum of Compound 6d Figure S21: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6e Figure S22: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6e Figure S23: HRESI-MS Spectrum of Compound 6e Figure S24: ESI-MS Spectrum of Compound 6e Figure S25: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6f Figure S26: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6f Figure S27: HRESI-MS Spectrum of Compound 6f Figure S28: ESI-MS Spectrum of Compound 6f Figure S29: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6g Figure S30: 13C -NMR (125 MHz, CDCl3) Spectrum of Compound 6g Figure S31: HRESI-MS Spectrum of Compound 6g Figure S32: ESI-MS Spectrum of Compound 6g Figure S33: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6h Figure S34: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6h Figure S35: HRESI-MS Spectrum of Compound 6h Figure S36: ESI-MS Spectrum of Compound 6h Figure S37: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6i Figure S38: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6i Figure S39: HRESI-MS Spectrum of Compound 6i Figure S40: ESI-MS Spectrum of Compound 6i Figure S41: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6j Figure S42: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6j Figure S43: HRESI-MS Spectrum of Compound 6j Figure S44: ESI-MS Spectrum of Compound 6j Figure S45: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6k Figure S46: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 6k Figure S47: HRESI-MS Spectrum of Compound 6k Figure S48: ESI-MS Spectrum of Compound 6k, Peer reviewed

Table of Content 1. Supplemental Figures 2. Supplemental Note a. Research electronic data capture (REDCap) b. Genetic risk score and multinomial regression on severity scale c. Evaluating the associations of leading SNPs in relation with comorbidities d. Measuring genome-specific effects on COVID-19 severity and hospitalization 3. Supplemental references 4. A full list of cohort members and affiliations a. SCOURGE cohort group b. HOSTAGE cohort group c. GR@ACE cohort group, Peer reviewed

Figure S1: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 1 Figure S2: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 1 Figure S3: ESI-MS Spectrum of Compound 1 Figure S4: HRHRESI-MS Spectrum of Compound 1 Figure S5: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 2 Figure S6: 13C-NMR (125 MHz, CDCl3) Spectrum of Compound 2 Figure S7: ESI-MS Spectrum of Compound 2 Figure S8: HRESI-MS Spectrum of Compound 2 Figure S9: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 3 Figure S10: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 3 Figure S11: ESI-MS Spectrum of Compound 3 Figure S12: HRESI-MS Spectrum of Compound 3 Figure S13: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 4 Figure S14: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 4 Figure S15: ESI-MS Spectrum of Compound 4 Figure S16: HRESI-MS Spectrum of Compound 4 Figure S17: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 5 Figure S18: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 5 Figure S19: ESI-MS Spectrum of Compound 5 Figure S20: HRESI-MS Spectrum of Compound 5 2 Figure S21: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 6 Figure S22: 13C-NMR (126 MHz, CDCl3) Spectrum of Compound 6 Figure S23: ESI-MS Spectrum of Compound 6 Figure S24: HRESI-MS Spectrum of Compound 6 Figure S25: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 7 Figure S26: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 7 Figure S27: ESI-MS Spectrum of Compound 7 Figure S28: HRESI-MS Spectrum of Compound 7 Figure S29: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 8 Figure S30: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 8 Figure S31: ESI-MS Spectrum of Compound 8 Figure S32: HRESI-MS Spectrum of Compound 8 Figure S33: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 9 Figure S34: 13C-NMR (126 MHz, CDCl3) Spectrum of Compound 9 Figure S35: ESI-MS Spectrum of Compound 9 Figure S36: HRESI-MS Spectrum of Compound 9 Figure S37: 1H-NMR (500 MHz, CDCl3) Spectrum of Compound 10 Figure S38: 13C-NMR (126 MHz, CDCl3) Spectrum of Compound 10 Figure S39: ESI-MS Spectrum of Compound 10 Figure S40: HRESI-MS Spectrum of Compound 10 Figure S41: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 11 Figure S42: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 11 Figure S43: ESI-MS Spectrum of Compound 11 Figure S44: HRESI-MS Spectrum of Compound 11 Figure S45: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 12 Figure S46: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 12 Figure S47: ESI-MS Spectrum of Compound 12 Figure S48: HRESI-MS Spectrum of Compound 12 Figure S49: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 13 Figure S50: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 13 Figure S51: ESI-MS Spectrum of Compound 13 Figure S52: HRESI-MS Spectrum of Compound 13 Figure S53: 1H-NMR (400 MHz, CDCl3) Spectrum of Compound 14 Figure S54: 13C-NMR (101 MHz, CDCl3) Spectrum of Compound 14 Figure S55: ESI-MS Spectrum of Compound 14 Figure S56: HRESI-MS Spectrum of Compound 14, Peer reviewed

Description of Additional Supplementary Files: File Name: Supplementary Data 1 Description: The file includes all statistics from linear regression model performed in the manuscript, including meqtl analysis. File Name: Supplementary Data 2 Description: Individual collected clinical information., Peer reviewed

Supplemental Table S1. Complete overview of the inclusion and exclusion criteria for this study. Supplemental Table S2. Composition of the EuroFlow B-cell panel and technical information on the reagents for the IMI-2 PERISCOPE BERT study. Supplemental Table S3. Phenotypic descriptions used to define B-cell subsets stained with the EuroFlow B-cell panel by manual analysis. Supplemental Table S4. Baseline distribution of leukocytes, lymphocytes, T cells, and NK cells in donor groups. Supplemental Table S5. Spearman Ranking Correlation between IgG1+ plasma cell and memory B-cell kinetics and vaccine-component-specific serum IgG. Supplemental Table S6. Spearman Ranking Correlation between IgA1+ plasma cell and IgA memory B-cell kinetics and vaccine-component-specific serum IgA. Supplemental Figure S1. No clear over-time postvaccination changes in major populations in any of the donor groups. Supplemental Figure S2. Over-time maturation of total plasma cells. Supplemental Figure S3. No significant changes in IgG1+ memory B-cell subsets upon vaccination. Supplemental Figure S4. Correlation between cellular changes as measured by flow cytometry and ELISpot. Supplemental Figure S5. Correlation between cellular changes and the vaccine-specific serum IgG level postvaccination as determined by Spearman’s Ranking Correlation per age cohort. Supplemental Figure S6. Impact of sex on cellular responses after vaccination in the young adult cohort (all wP-primed). Supplemental Figure S7. IgG1+ and total plasma cell expansion is more prominent in non-age-matched donors after wP priming., Peer reviewed

CiberAMP is an R package that uses differential expression analyses to stablish accurate correlations between specific SCNVs and changes in expression in the genes affected by them. The algorithm has been designed to be an easy-to-access tool for the TCGA, the largest database in the world with genomic and transcriptomic data ofr more than 10,000 samples of 33 different human cancers. Unlike other methods, CiberAMP can yield information on: (i) SCNV-DEGs (somatic copy number variations associated differentially expressed genes) in a cohort of TCGA tumor samples (ii) The type of copy number variation associated with each SCNV-DEG in terms of expression pattern and genomic context (iii) Insights on the potential functional relevance of each identified SCNV-DEG, Peer reviewed

The promoter‐less CRISPR‐Trap system efficiently the specific integration of the gene trap donor in BCR/ABL but is not a robust reporter system to select corrected cells. As a first approach, we generate a dsDNA donor by PCR amplification containing a SAT2A‐ Venus interfering cassette (Figure S1A). The K562 cell line was divided into three experimental groups according to the conditions for their subsequent electroporation: a) with the donor dsDNA (donor), b) with the donor DNA and Cas9 nuclease without sgRNA (Cas9 + donor) and c) with the donor DNA, Cas9 nuclease and the specific BCR/ABL sgRNA (CRISPR/Cas9 + donor). Twenty‐four hours after electroporation, no fluorescent cells (Venus + cells) were observed in any of the three groups (Figure S1B). The result of the site‐unspecific PCR (In 5´F/Venus R, Table 1) which amplify a region contained entirely in the donor HDR dsDNA, showed a band of the expected size in the Cas9 + donor and CRISPR/Cas9 + donor groups, but not in the donor group (Figure S1C), implying that all donor HDR dsDNA not integrated in the genome was fully degraded. In contrast, the sitespecific PCR (Out 5´F/Venus R, Table 1) corroborated the correct insertion of the donor HDR dsDNA at the BCR/ABL target sequence only in the CRISPR/Cas9 + donor group, with no sitespecific integration detected in any of the controls (Figure S1C). These results were corroborated by Sanger sequencing of the PCR products, supporting the HDR‐mediated insertion of the donor dsDNA into the CRISPR/Cas9 + donor group., Peer reviewed

The following are available online at https://www.mdpi.com/article/10.3390/cancers14020449/s1. Supplementary Figures. Figure S1: Distribution of pathological CSF samples (without healthy ones) among each phase of study and the different groups according to the incidence of the pathology, depending on the infiltration (CSF +/− LM) and the primary tumor (hematologic and solid tumor). Figure S2: Quality control images of the planar protein microarrays generated. Figure S3: A quantile normalization in planar protein microarrays. Figure S4: Coomasie gels which indicate protein distribution across samples. Figure S5: Venn diagrams of total identified proteins with LC-MS/MS. Figure S6: Plots showing the functional proteins using the Reactome for different conditions. Figure S7: Differential protein profiles within CSF + LM according to primary tumor (Lymphoma) by protein microarrays. Figure S8: Differential protein profiles within CSF + LM according to primary tumor (Leukemia) by protein microarrays. Figure S9: Differential protein profiles within CSF + LM according to primary tumor (Lymphoma) by affinity proteomics. Figure S10: Differential protein profiles within CSF + LM according to primary tumor (Leukemia) by affinity proteomics. Figure S11: Summary of the multipronged proteomics characterization among the different phases of study. Supplementary Tables. Table S1: Table of clinical-biological characteristics from the whole CSF samples used in the study. Table S2: Antibodies list used in Planar Protein Microarrays. Table S3: Antibodies list used in Beads Suspension Microarrays. Table S4: Protein identification with LC-MS/MS among the different strategies and their emPAI quantification. Table S5: Boxplots of the protein identified in validation and confirmation phases, respectively, comparing the different groups of study. Table S6: Intensity data results from Planar Protein Microarrays. Table S7: Intensity data results from Beads Suspension Microarrays. Table S8: ROC analysis list of potential biomarker panel on CSF +/− LM and the different comparisons by protein arrays and affinity proteomics., Peer reviewed