Uracil in DNA may therefore be used as a key marker for estimating efficiency of chemotherapeutic drugs targeting thymidylate biosynthesis

Uracil in DNA may therefore be used as a key marker for estimating efficiency of chemotherapeutic drugs targeting thymidylate biosynthesis. patterns and selected histone marks or transcription factors. elife-60498-fig4-data1.xlsx (47K) GUID:?E6FE7466-ED71-45C8-AF15-3CA2359E69E2 Figure 4source data 2: Signal distribution data from genome segmentation analysis by Segway. elife-60498-fig4-data2.xlsx (55K) GUID:?58DA68BD-F5CE-4D34-897D-8E96AA27E87A Figure 4source data 3: Correlation between U-DNA patterns and replication timing. elife-60498-fig4-data3.xlsx (61M) GUID:?3C4C1722-E62C-47B7-8321-2C523BE9CAEA Figure 4figure supplement 3source data 1: Replication timing scores and AT content calculated on genomic segments that were determined by the?Segway?analysis. elife-60498-fig4-figsupp3-data1.xlsx (250K) GUID:?F63F7FD6-2B4E-4C9E-AD44-CB39162A7FE6 Figure 8source data 1: Interaction factors between U-DNA and selected histone marks, determined in colocalization measurements using dSTORM microscopy. elife-60498-fig8-data1.xlsx (25K) GUID:?AEAB08D4-6648-4512-A3D2-BD5FB4AC99C1 Supplementary file 1: Detailed analysis pipeline C methods of U-DNA-Seq data analysis. List of the investigated samples LPA2 antagonist 1 (table 1); list of applied tools (table 2); pre-processing including blacklisting and additional statistics (table 3); and methods to determine uracil enrichment pattern. All applied processing steps are given in generalized command lines. elife-60498-supp1.pdf (698K) GUID:?67ED3043-33EC-47CB-BA57-F9FE0804FC81 Supplementary file 2: IGV views of log2 ratio and regions of uracil enrichment on all the chromosomes. elife-60498-supp2.pdf (3.2M) GUID:?135D5325-1E5A-401C-BE6E-0D69CD6CAD6A Supplementary file 3: Genome-wide analysis of uracil-DNA pattern comparing to ChIP-seq data and DNA accessibility data using either GIGGLE search or the Segway genome segmentation tool. Database information, applied command lines, full results of GIGGLE search (table 1), details of our own ChIP-seq (table 2), and list of files for Segway analysis (table 3) are provided. elife-60498-supp3.pdf (1.3M) GUID:?BE94259D-8A20-41E4-9496-6E1BAB4DC398 Supplementary file 4: Genome-wide analysis of uracil-DNA pattern comparing to other genomic features using bedtools annotate. Database information, applied command ITSN2 lines, full results (table 1), and calculation of replication timing scores and AT content on genomic segments (from the Segway analysis) are provided. elife-60498-supp4.pdf (355K) GUID:?B8F36E94-4E8A-4C98-87C2-E2EA2D88E12D Supplementary file 5: Detailed comparison of U-DNA pattern to replication timing data (R script). elife-60498-supp5.pdf (122K) GUID:?8E68FC50-6954-4825-B601-198BFBA3C4C9 Transparent reporting form. elife-60498-transrepform.pdf (690K) GUID:?AEB9F843-91C5-4F20-A9BA-A884508413B7 Appendix 1figure 1source data 1: Comparison of histograms for the U-DNA signal distributions between dU-seq and U-DNA-Seq data. elife-60498-app1-fig1-data1.xlsx (35K) GUID:?A2F46A19-963F-43BA-9DE0-E7581CBEF157 Appendix 1figure 2source data 1: Comparison of dU-seq and U-DNA-Seq data regarding correlation between U-DNA patterns and replication timing. elife-60498-app1-fig2-data1.xlsx (51M) GUID:?9FCF6226-A00B-4A87-ABB6-415D213B99F7 Data Availability StatementSequencing data have been deposited into the Gene Expression Omnibus (GEO) under accession number {“type”:”entrez-geo”,”attrs”:{“text”:”GSE126822″,”term_id”:”126822″}}GSE126822 and {“type”:”entrez-geo”,”attrs”:{“text”:”GSE153407″,”term_id”:”153407″}}GSE153407, which have been unified under SuperSeries {“type”:”entrez-geo”,”attrs”:{“text”:”GSE153408″,”term_id”:”153408″}}GSE153408. In the following Genome Browser session, we included all the log2 coverage ratio (bigwig) and the derived uracil enriched interval (bed) files corresponding to this manuscript. The color LPA2 antagonist 1 code LPA2 antagonist 1 and the names are the same as used here. https://genome.ucsc.edu/s/bekesiangi/GSE126822_UCSC_Genome_Browser_session. Source data have been provided for Figure 1-figure supplement 1, Figure 2-figure supplement 2, Figure 3, Figure 3-figure supplement 4, Figure 4, Figure 4-figure supplement 3, Figure 8, Appendix 1-figure 1, Appendix 1-figure 2. The following datasets were generated: Plinks HL, Bksi A, Pongor L, Holub E, Papp G, Gemma C, Ali S, Gy?rffy B, Vrtessy BG. 2020. Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments. NCBI Gene Expression Omnibus. GSE126822 Plinks HL, Bksi A, Vrtessy BG. 2020. H3K36me3 ChIP-seq in non-treated and raltitrexed treated UGI-expressing HCT116 cells. NCBI Gene Expression Omnibus. GSE153407 The following previously published dataset was used: Shu X, Lu Z, Yi C. 2018. Genome-wide mapping reveals that deoxyuridine is enriched in the human centromeric DNA. NCBI Gene Expression Omnibus. GSE99011 Abstract Numerous anti-cancer drugs perturb thymidylate biosynthesis and lead to genomic uracil incorporation contributing to their antiproliferative effect. Still, it is not yet characterized if uracil incorporations have any positional preference. Here, we aimed to uncover genome-wide alterations in uracil.