DOI: 10.5061/dryad.q573n5twd
title: Data from: Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy

description: These data are the original data used to produce the figures, tables, and
 supplemental information for the manuscript "Epigenetic small
 molecule screening identifies a new HDACi compound for ameliorating
 Duchenne muscular dystrophy". In this study, our goal was to identify
 histone deacetylase inhibitors (HDACi), or other classes of epigenetic
 small molecules that are beneficial for DMD. Using an established animal
 model for DMD, the zebrafish dmd mutant strain sapje, we screened
 a library of over 800 epigenetic small molecules. Our screening identified
 a new HDACi, SR-4370, that ameliorated dmd mutant zebrafish skeletal
 muscle degeneration, as well as additional HDACi that have previously been
 shown to improve dmd zebrafish. We find that a single early treatment of
 HDACi can ameliorate the muscle phenotype and increase lifespan in dmd
 zebrafish. Furthermore, we find that HDACi treatments that improve dmd
 muscle also cause increased histone acetylation in zebrafish larvae. Our
 results add to the growing evidence that HDACi are promising candidates
 for treating DMD. Our study also provides further support for the
 effectiveness of small-molecule screening in dmd zebrafish.
description: # Epigenetic small molecule screening identifies a new HDACi compound for
 ameliorating Duchenne muscular dystrophy. Study Description:  The data
 presented here is an original dataset of the raw data underlying the
 figures in the publication "Epigenetic small molecule screening
 identifies a new HDACi compound for ameliorating Duchenne muscular
 dystrophy." In this publication, we used an established animal model
 for DMD, the zebrafish strain sapje, to screen a library of &gt;800
 epigenetic small molecules. We found that a single early treatment of the
 HDACi SR-4370 can ameliorate the muscle phenotype, increase lifespan in
 dmd zebrafish, and increase histone acetylation. These results support the
 effectiveness of small molecule screening in DMD zebrafish and add to the
 growing evidence of HDACi as promising candidates for treating DMD. The
 data was generated using the methods described in the resulting
 publication. Research Domain: Biological sciences Keywords: Duchenne
 muscular dystrophy, epigenetic therapy, HDAC inhibitor, zebrafish, drug
 screen Funding Information: This work was supported by the National
 Institutes of Health 5R01AR076978 and National Institutes of Health grant
 5R90DE023059. The funding sources had no involvement in the conduct of the
 research or preparation of the article. #### Data and File Overview Each
 file in this folder contains the raw data generated for this study. List
 of Tables and Files provided:  **table_1_qualitative_phenotypic_data.csv**
 This table provides the raw data underlying the graphs shown in Fig. 1D,
 S1, 2A-B, and S2. Due to the number of treatments and animals needed, the
 experimental batch is included as column 1. Treatment, concentration,
 duration, library plate, row, and column location are indicated in columns
 2-7. Numeric suffix on columns 8-27 indicates the biological replicate
 (i.e., 1-4) from which the data were obtained. "Dead" indicates
 generalized lethality within the corresponding biological replicate and
 exposure conditions. "Standard" indicates treatment from 24-96
 hours post-fertilization (hpf) as described in the methods and illustrated
 in Fig. 4B. WT, wild type. DMSO, dimethyl sulfoxide.
  **table_2_library_compounds.csv** This table lists all included compounds
 and their corresponding plate number and well locations (row/column
 format) in the screening library (MedChemExpress, Monmouth Junction, NJ;
 Catalog #HY-L005).  **table_3_pool_model.csv** This table lists
 pre-processed data underlying the graph shown inFig.2A. Data in this file
 was derived from and summarizes data in
 “table_1_qualitative_phenotypic_data.csv”. This file was subsequently run
 using the provided code (see CODE/SOFTWARE). WT, wild type. DMSO, dimethyl
 sulfoxide.  **table_4_qbiref_initial.csv** This table provides the raw
 data underlying graph 2D. Data shown are the raw mean gray values used in
 the quantitative birefringence analysis of wild type (WT) or mutant *dmd*
 larvae treated with the indicated compounds and concentrations. Column 1
 labeled "plate/well" refers to locations on 12-well testing
 plates and was used to identify and organize data into biological
 replicates. DMSO, dimethyl sulfoxide.
  **table_5_qbiref_compare_vendor.csv** This table provides the raw data
 underlying graph 3A. Data shown are the raw mean gray values used in the
 quantitative birefringence analysis of wild type (WT) or mutant *dmd*
 larvae treated with the indicated compounds and concentrations. Column 1
 labeled "plate/well" refers to locations on 12-well testing
 plates and was used to identify and organize data into biological
 replicates. DMSO, dimethyl sulfoxide.
  **table_6_qbiref_external_validation.csv** This table provides additional
 raw data underlying graph 3B. Data shown are the raw mean gray values used
 in the quantitative birefringence analysis of wild type (WT) or mutant
 *dmd* larvae treated with the indicated compounds and concentrations.
 These values (recorded at the University of Maine) were compared to data
 in “table_4_qbiref_initial.csv”, also shown in 2D.  DMSO, dimethyl
 sulfoxide.  **table_7_qbiref_SR_low.csv** This table provides the raw data
 underlying graph 4A. Data shown are the raw mean gray values used in the
 quantitative birefringence analysis of wild type (WT) or mutant *dmd*
 larvae treated with the indicated compounds and concentrations. Column 1
 labeled "plate/well" refers to locations on 12-well testing
 plates and was used to identify and organize data into biological
 replicates. DMSO, dimethyl sulfoxide.  **table_8_qbiref_SR_high.csv** This
 table provides the raw data underlying graph 4A. Data shown are the raw
 mean gray values used in the quantitative birefringence analysis of wild
 type (WT) or mutant *dmd* larvae treated with the indicated compounds and
 concentrations. Column 1 labeled "plate/well" refers to
 locations on 12-well testing plates and was used to identify and organize
 data into biological replicates. DMSO, dimethyl sulfoxide.
  **table_9_qbiref_SR_times.csv** This table provides the raw data
 underlying graph 4C. Data shown are the raw mean gray values used in the
 quantitative birefringence analysis of wild type (WT) or mutant *dmd*
 larvae treated with the indicated compounds, concentrations, and from the
 indicated time in hours post-fertilization (hpf). Column 1 labeled
 "plate/well" refers to locations on 12-well testing plates and
 was used to identify and organize data into biological replicates. DMSO,
 dimethyl sulfoxide.  **table_10_myotomes.csv** This table provides the raw
 data underlying graph 4G. Data shown are the raw counts of
 affected/lesioned or unaffected/normal myotomes in wild-type (WT) or
 mutant *dmd* larvae treated with the indicated compounds and
 concentrations. DMSO, dimethyl sulfoxide.  **table_11_qbiref_ox_row.csv**
 This table provides the raw data underlying graph 5A. Data shown are the
 raw mean gray values used in the quantitative birefringence analysis of
 wild type (WT) or mutant *dmd* larvae treated with the indicated compounds
 and concentrations. Column 1 labeled "plate/well" refers to
 locations on 12-well testing plates and was used to identify and organize
 data into biological replicates. DMSO, dimethyl sulfoxide.
  **table_12_qbiref_ox_col.csv** This table provides the raw data
 underlying graph 5A. Data shown are the raw mean gray values used in the
 quantitative birefringence analysis of wild type (WT) or mutant *dmd*
 larvae treated with the indicated compounds and concentrations. Column 1
 labeled "plate/well" refers to locations on 12-well testing
 plates and was used to identify and organize data into biological
 replicates. DMSO, dimethyl sulfoxide.  **table_13_qbiref_ox_indiv.csv**
 This table provides the raw data underlying graph 5B. Data shown are the
 raw mean gray values used in the quantitative birefringence analysis of
 wild type (WT) or mutant *dmd* larvae treated with the indicated compounds
 and concentrations. Column 1 labeled "plate/well" refers to
 locations on 12-well testing plates and was used to identify and organize
 data into biological replicates. DMSO, dimethyl sulfoxide.
  **table_14_qbiref_ox_elim.csv** This table provides the raw data
 underlying graph 5C. Data shown are the raw mean gray values used in the
 quantitative birefringence analysis of wild type (WT) or mutant *dmd*
 larvae treated with the indicated compounds and concentrations. Column 1
 labeled "plate/well" refers to locations on 12-well testing
 plates and was used to identify and organize data into biological
 replicates. DMSO, dimethyl sulfoxide.  **table_15_qbiref_ox_pairwise.csv**
 This table provides the raw data underlying graph 5D. Data shown are the
 raw mean gray values used in the quantitative birefringence analysis of
 wild type (WT) or mutant *dmd* larvae treated with the indicated compounds
 and concentrations. Column 1 labeled "plate/well" refers to
 locations on 12-well testing plates and was used to identify and organize
 data into biological replicates. DMSO, dimethyl sulfoxide.
  **table_16_qbiref_hdaci.csv** This table provides the raw data underlying
 graph 6A. Data shown are the raw mean gray values used in the quantitative
 birefringence analysis of wild type (WT) or mutant *dmd* larvae treated
 with the indicated compounds and concentrations. Column 1 labeled
 "plate/well" refers to locations on 12-well testing plates and
 was used to identify and organize data into biological replicates. DMSO,
 dimethyl sulfoxide.  **table_17_qbiref_hdaci_add.csv** This table provides
 the raw data underlying graph 6A. Data shown are the raw mean gray values
 used in the quantitative birefringence analysis of wild type (WT) or
 mutant *dmd* larvae treated with the indicated compounds and
 concentrations. Column 1 labeled "plate/well" refers to
 locations on 12-well testing plates and was used to identify and organize
 data into biological replicates. DMSO, dimethyl sulfoxide.
  **table_18_western_hdaci.csv** This table provides the raw data
 underlying graphs 6D-F. Data shown are the raw band intensities in Western
 analysis of wild type (WT) or mutant *dmd* larvae treated with the
 indicated compounds and concentrations. Column "gel" refers to
 the gel image (as shown in Supplemental Figure S3) from which measurements
 were obtained. DMSO, dimethyl sulfoxide.  **table_19_survival.csv** This
 table provides the raw data underlying graph 7A. The data shown are the
 raw counts of surviving larvae treated with the indicated compounds.
 Column "dpf" indicates the day post-fertilization at which
 animals were counted. Column names specify compound, replicate, and lesion
 status (i.e., AFFECTED or unaffected) of each recorded tank. WT, wild
 type. DMSO, dimethyl sulfoxide.  **table_20_survival_multiple.csv** This
 table provides the raw data underlying graph 7B. The data shown are the
 raw counts of surviving larvae treated with the indicated compounds.
 Column "dpf" indicates the day post-fertilization at which
 animals were counted. Column names specify compound, replicate, and lesion
 status (i.e., AFFECTED or unaffected) of each recorded tank. WT, wild
 type. DMSO, dimethyl sulfoxide. **regression_analysis.txt** This file
 contains the R script used to generate data underlying the graph shown in
 Fig. 2A. Data format from “table_3_pool_model.csv” should be retained, and
 code should be executed in order. Default settings were used for analysis.
 ## Code/Software Regression analysis was run in R v4.4.1 using the package
 GLM v14. Analysis also requires the tidyverse package to be loaded in the
 environment. Raw data for replicates in file
 "table_1_qualitative_phenotypic_data.csv" were aggregated and
 simplified to generate the starting file
 "table_3_pool_model.csv". To recreate the analysis, data should
 be kept in the same format, and the code in “regression_analysis.txt”
 should be executed in order.