Chemical modulation of Schistosoma mansoni lysine specific demethylase 1 (SmLSD1) induces wide-scale biological and epigenomic changes - Supplementary tables and movies

Extended data This project contains the following extended data: Table S1. Chemical structures of the 39 compounds included in this study. Table S2. Z´ values for both phenotype and motility of the Roboworm screens performed on the 39 compounds. Table S3. Z´ values for both phenotype and motility of the Roboworm screens performed on the titration of the five selected compounds (compounds 15, 16, 33, 35 and 36). Table S4A. List of the 71,859 ATAC-Seq peaks found in the female dataset Table S4B. List of corresponding 844 genomic loci associated to statistically significant ATAC-seq differences (adjusted p-value ≤0.05) following compound 33 treatment (female dataset) Table S4C. List of the 84,997 ATAC-Seq peaks found in male dataset Table S4D. List of corresponding 2,107 genomic loci associated to statistically significant ATAC-seq differences (adjusted p-value ≤0.05) following compound 33 treatment (male dataset) Table S4E. List of female and male genes associated to statistically significant ATAC-seq differences between compound 33 and mock treatments. Table S5A. List of the 844 genomic loci associated to statistically significant ATAC-seq differences (female subset). The table contains the gene ID, chromosome position, start and end of the ATAC-seq peak position, ATAC-seq peak identifier, value of log2-foldchange (log2FC). Table S5B. Occurrence of ATAC-seq peaks (accessible chromatin) per genes (female subset). The table contains the gene ID and the associated number of ATAC-seq peaks Table S5C. List of ATAC-seq positive signals (accessible chromatin) found in the mock female samples (filtered from S5A Table with log2FC>0) Table S5D. List of ATAC-seq positive signals (accessible chromatin) found in the compound 33-treated female samples (filtered from S5A Table with log2FC<0) Table S5E. List of female genes containing higher ATAC-seq positive signals (accessible chromatin) in compound 33-treated samples. The table contains the gene ID, the number of associated ATAC-seq peaks and the average log2FC across all the peaks associated with each gene (log2FC<0 corresponds to higher ATAC-seq positive signals found in the compound 33 treated samples). Table S5F. List of female genes containing higher ATAC-seq positive signals (accessible chromatin) in mock samples. The table contains the gene ID, the number of associated ATAC-seq peaks and the average log2FC value across all the peaks associated to each gene (log2FC>0 corresponds to higher ATAC-seq positive signals found in the control treatment). Table S6A. List of corresponding 2,107 genomic loci associated with statistically significant ATAC-seq differences (male subset). The table contains the gene ID, chromosome position, start and end of the ATAC-seq peak position, ATAC-seq peak identifier, value of log2-foldchange (log2FC). Table S6B. Occurrence of ATAC-seq peaks per genes (male subset). The table contains the gene ID and the associated number of ATAC-seq peaks Table S6C. List of ATAC-seq positive signals (accessible chromatin) found in the mock male samples (filtered from S6A Table with log2FC>0) Table S6D. List of ATAC-seq positive signals (accessible chromatin) found in the compound 33-treated male samples (filtered from S6A Table with log2FC<0) Table S6E. List of male genes associated with higher ATAC-seq positive signals (accessible chromatin) in compound 33-treated samples. The table contains the gene ID, the number of associated ATAC-seq peaks and the average log2FC across all the peaks associated to each gene (log2FC<0 corresponds to higher ATAC-seq positive signals found in the compound 33 treated samples). Table S6F. List of male genes associated with higher ATAC-seq positive signals (accessible chromatin) in mock samples. The table contains the gene ID, the number of associated ATAC-seq peaks and the average log2FC value across all the peaks associated with each gene (log2FC>0 corresponds to higher ATAC-seq positive signals found in the control treatment). Table S7. List of the structure, the docking score and EC50 values (on schistosomula and adult worms) of the five most active compounds. Table S8. List of 24 adult worm ATAC-seq sample IDs, primer sequences and additional PCR cycles used for preparation of ATAC-seq libraries Table S9. Excel workbook used for the hypergeometric test for overrepresentation of ATAC-Seq signal within the available scRNA-Seq data derived from adult worms [70]. Movie S1. Video of S. mansoni compound 33-treated (3.13 µM, right-hand side) and control (DMSO, left-hand side) worm pairs after 72 h incubation in tissue culture wells. Notice the lack of parasite attachment and the presence of cellular material within the compound treated well. Movie S2. Serial optical sections of DAPI-stained, S. mansoni egg. Comparison between the compound 33-treated (3.13 µM, right-hand side) and the negative control (DMSO, left-hand side) egg is provided. Movie S3. Serial optical sections of S. mansoni adult female worm stained with DAPI and EdU. In these series of optical sections, three different anatomical regions (anterior region, gonadal system and posterior region, from left to right) of the worm were observed. Comparison between the negative control (DMSO, first row) and the compound 33-treated (3.13 µM, second row) parasites is provided. Movie S4. Serial optical sections of S. mansoni adult male worm stained with DAPI and EdU. In these series of optical sections, three different anatomical regions (anterior region, gonadal system and posterior region, from left to right) of the worm were observed. Comparison between the negative control (DMSO, first row) and the compound 33-treated (3.13 µM, second row) parasites is provided.

补充数据
本项目包含如下补充数据：
表S1 本研究纳入的39种化合物的化学结构。
表S2 针对39种化合物开展的Roboworm筛选中，表型与运动性对应的Z'因子（Z'-factor）值。
表S3 针对5种选定化合物（化合物15、16、33、35和36）的梯度稀释实验开展的Roboworm筛选中，表型与运动性对应的Z'因子值。
表S4A 雌性数据集中共鉴定到的71859个转座酶可及性测序（ATAC-Seq）峰列表。
表S4B 经化合物33处理后（雌性数据集），与具有统计学显著性的ATAC-Seq差异相关的844个基因组位点列表（校正后P值≤0.05）。
表S4C 雄性数据集中共鉴定到的84997个ATAC-Seq峰列表。
表S4D 经化合物33处理后（雄性数据集），与具有统计学显著性的ATAC-Seq差异相关的2107个基因组位点列表（校正后P值≤0.05）。
表S4E 与化合物33处理组和空白对照（mock）处理组间具有统计学显著性的ATAC-Seq差异相关的雌雄基因列表。
表S5A 与具有统计学显著性ATAC-Seq差异相关的844个基因组位点列表（雌性亚组）。该表格包含基因ID、染色体位置、ATAC-Seq峰的起始与终止位点、ATAC-Seq峰标识符以及log2倍数变化（log2-fold change, log2FC）值。
表S5B 每个基因对应的ATAC-Seq峰（开放染色质）出现频次列表（雌性亚组）。该表格包含基因ID及其关联的ATAC-Seq峰数量。
表S5C 空白对照雌性样本中检测到的ATAC-Seq阳性信号（开放染色质）列表（从表S5A中筛选log2FC>0的结果）。
表S5D 化合物33处理雌性样本中检测到的ATAC-Seq阳性信号（开放染色质）列表（从表S5A中筛选log2FC<0的结果）。
表S5E 在化合物33处理样本中具有更高ATAC-Seq阳性信号（开放染色质）的雌性基因列表。该表格包含基因ID、关联的ATAC-Seq峰数量以及每个基因所有关联峰的平均log2FC值（log2FC<0对应化合物33处理样本中更高的ATAC-Seq阳性信号）。
表S5F 在空白对照样本中具有更高ATAC-Seq阳性信号（开放染色质）的雌性基因列表。该表格包含基因ID、关联的ATAC-Seq峰数量以及每个基因所有关联峰的平均log2FC值（log2FC>0对应空白对照处理样本中更高的ATAC-Seq阳性信号）。
表S6A 与具有统计学显著性ATAC-Seq差异相关的2107个基因组位点列表（雄性亚组）。该表格包含基因ID、染色体位置、ATAC-Seq峰的起始与终止位点、ATAC-Seq峰标识符以及log2倍数变化（log2FC）值。
表S6B 每个基因对应的ATAC-Seq峰出现频次列表（雄性亚组）。该表格包含基因ID及其关联的ATAC-Seq峰数量。
表S6C 空白对照雄性样本中检测到的ATAC-Seq阳性信号（开放染色质）列表（从表S6A中筛选log2FC>0的结果）。
表S6D 化合物33处理雄性样本中检测到的ATAC-Seq阳性信号（开放染色质）列表（从表S6A中筛选log2FC<0的结果）。
表S6E 在化合物33处理样本中具有更高ATAC-Seq阳性信号（开放染色质）的雄性基因列表。该表格包含基因ID、关联的ATAC-Seq峰数量以及每个基因所有关联峰的平均log2FC值（log2FC<0对应化合物33处理样本中更高的ATAC-Seq阳性信号）。
表S6F 在空白对照样本中具有更高ATAC-Seq阳性信号（开放染色质）的雄性基因列表。该表格包含基因ID、关联的ATAC-Seq峰数量以及每个基因所有关联峰的平均log2FC值（log2FC>0对应空白对照处理样本中更高的ATAC-Seq阳性信号）。
表S7 5种活性最高的化合物的结构、对接得分以及（针对血吸虫童虫和成虫的）半最大效应浓度（EC50）值列表。
表S8 24个成虫ATAC-Seq样本的ID、引物序列以及制备ATAC-Seq文库所用的额外PCR循环数列表。
表S9 用于超几何检验的Excel工作簿，用于检验现有成虫来源的单细胞RNA测序（scRNA-Seq）数据中ATAC-Seq信号的富集情况[70]。
视频S1 曼氏血吸虫（S. mansoni）经化合物33处理（3.13 µM，右侧）与对照（二甲基亚砜（DMSO），左侧）的虫体配对样本在组织培养孔中孵育72小时后的影像。可见处理组虫体失去附着能力，且培养孔内存在细胞物质。
视频S2 经4',6-二脒基-2-苯基吲哚（DAPI）染色的曼氏血吸虫虫卵连续光学切片影像。对比展示了化合物33处理组（3.13 µM，右侧）与阴性对照（DMSO，左侧）的虫卵。
视频S3 经DAPI和5-乙炔基-2'-脱氧尿苷（EdU）染色的曼氏血吸虫成虫雌性虫体连续光学切片影像。该系列切片依次观察了虫体的三个不同解剖区域（从左至右分别为前部区域、生殖系统和后部区域），对比展示了阴性对照（DMSO，第一行）与化合物33处理组（3.13 µM，第二行）的寄生虫。
视频S4 经DAPI和EdU染色的曼氏血吸虫成虫雄性虫体连续光学切片影像。该系列切片依次观察了虫体的三个不同解剖区域（从左至右分别为前部区域、生殖系统和后部区域），对比展示了阴性对照（DMSO，第一行）与化合物33处理组（3.13 µM，第二行）的寄生虫。