DOI: 10.5061/dryad.q573n5tx2
title: Data from: Layer-specific proteomic analysis of human hearts in patients with sudden cardiac death

description: Recent studies have shown that decreased longitudinal strain in
 speckle-tracking echography can predict sudden cardiac death (SCD) in
 patients with cardiac hypertrophy (CH). Histologically, the heart wall
 consists of the inner longitudinal, middle circular, and outer
 longitudinal layers. Thus, layer-specific proteomic changes may contribute
 to SCD risk. The three layers in human cardiac tissues were obtained
 during autopsies of SCD, compensated CH, and control cases (18 cases aged
 &gt; 40 years, 54 samples in total). SCD cases consisted of patients
 with ischemic or hypertensive heart failure, whereas CH and control cases
 were accidental deaths. After histological analysis, cardiomyocytes were
 collected separately from the three layers of the left ventricular wall
 using laser microdissection. The extracted proteins were analyzed using
 liquid chromatography–tandem mass spectrometry, followed by label-free
 quantification. Histologically, cardiomyocytes were enlarged in all layers
 of SCD and CH cases without significant progression of myocardial
 fibrosis. The proteomic profiles of SCD and CH cases were distinguishable
 from those of control cases, especially in the inner layer. The levels of
 mitochondrial and calcium-handling proteins were significantly decreased
 in SCD hearts. Arrhythmogenic changes, including decreased PKP2 and RYR2
 levels, developed in a stepwise manner from control through CH to SCD,
 most prominently in the inner layer. Immunohistochemical analysis showed
 reduced levels of PKP2 in intercalated disks and RYR2 in sarcomeres.
 Because proteomic alterations precede the progression of myocardial
 fibrosis, their detection may enhance the accuracy of postmortem diagnosis
 of SCD in middle-aged and older asymptomatic individuals with CH.
description: # Data from: Layer-specific proteomic analysis of human hearts in patients
 with sudden cardiac death Dataset DOI:
 [10.5061/dryad.q573n5tx2](https://doi.org/10.5061/dryad.q573n5tx2) ##
 Description of the data and file structure Proteome profiles were
 individually determined by using a Q Exactive mass spectrometer (Thermo
 Fisher Scientific) equipped with an UltiMate 3000 LC system (Thermo Fisher
 Scientific). All patients were divided into three groups: SCD, CH, and
 Control. All samples were dissected from three myocardial layers: inner
 longitudinal layer (I), middle circular layer (M), and outer longitudinal
 layer (O) using laser microdissection (LMD 6500; Leica Microsystems,
 Wetzlar, Germany) Note: The mznld files contain raw MS data, while the
 three CSV files contain processed quantitative protein data extracted from
 those mznld files. Each CSV file contains protein-level quantification
 results for one myocardial layer. ## Description of the data and file
 structure File name includes sample group and layer information. For
 example: SCD1_I.mznld: "SCD1" corresponds tothe  sample group,
 and id "I"corresponds to the layer (Inner longitudinal
 layer, Middle circular layer, er and Outer longitudinal layer) The .mznld
 files are raw data export files generated by Progenesis QI for
 Proteomics. Each heart was dissected into three myocardial layers before
 proteomic analysis. They contain: * MS1 full scan spectra (300–1500 m/z) *
 MS/MS (HCD) spectra of the top 20 most abundant precursor ions * Peptide
 peak lists * Quantitative intensity information * Alignment and
 normalization data * Protein inference information ### Files and variables
 File: SCD1_I.mznld Description: SCD, inner layer File: SCD2_I.mznld
 Description: SCD, inner layer File: CH1_I.mznld Description: CH, inner
 layer File: SCD3_I.mznld Description: SCD, inner layer File: SCD4_I.mznld
 Description: SCD, inner layer File: CH2_I.mznld Description: CH, inner
 layer File: SCD5_I.mznld Description: SCD, inner layer File: CH3_I.mznld
 Description: CH, inner layer File: SCD6_I.mznld Description: SCD, inner
 layer File: CH4_I.mznld Description: CH, inner layer File: SCD7_I.mznld
 Description: SCD, inner layer File: SCD8_I.mznld Description: SCD, inner
 layer File: CH5_I.mznld Description: CH, inner layer File: SCD1_M.mznld
 Description: SCD, middle layer File: SCD2_M.mznld Description: SCD, middle
 layer File: CH1_M.mznld Description: CH, middle layer File: SCD3_M.mznld
 Description: SCD, middle layer File: SCD4_M.mznld Description: SCD, middle
 layer File: CH2_M.mznld Description: CH, middle layer File: SCD5_M.mznld
 Description: SCD, middle layer File: CH3_M.mznld Description: CH, middle
 layer File: SCD6_M.mznld Description: SCD, middle layer File: CH4_M.mznld
 Description: CH, middle layer File: SCD8_M.mznld Description: SCD, middle
 layer File: SCD7_M.mznld Description: SCD, middle layer File: CH5_M.mznld
 Description: CH, middle layer File: SCD1_O.mznld Description: SCD, outer
 layer File: SCD2_O.mznld Description: SCD, outer layer File: CH1_O.mznld
 Description: CH, outer layer File: SCD3_O.mznld Description: SCD, outer
 layer File: SCD4_O.mznld Description: SCD, outer layer File: CH2_O.mznld
 Description: CH, outer layer File: SCD5_O.mznld Description: SCD, outer
 layer File: CH3_O.mznld Description: CH, outer layer File: CH4_O.mznld
 Description: CH, outer layer File: SCD6_O.mznld Description: SCD, outer
 layer File: SCD7_O.mznld Description: SCD, outer layer File: SCD8_O.mznld
 Description: SCD, outer layer File: CH5_O.mznld Description: CH, outer
 layer File: Ctl1_I.mznld Description: Control, inner layer File:
 Ctl2_I.mznld Description: Control, inner layer File: Ctl3_I.mznld
 Description: Control, inner layer File: Ctl4_I.mznld Description: Control,
 inner layer File: Ctl5_I.mznld Description: Control, inner layer File:
 Ctl1_M.mznld Description: Control, middle layer File: Ctl2_M.mznld
 Description: Control, middle layer File: Ctl3_M.mznld
 Description: Control, middle layer File: Ctl4_M.mznld
 Description: Control, middle layer File: Ctl5_M.mznld
 Description: Control, middle layer File: Ctl1_O.mznld
 Description: Control, outer layer File: Ctl2_O.mznld Description: Control,
 outer layer File: Ctl3_O.mznld Description: Control, outer layer File:
 Ctl4_O.mznld Description: Control, outer layer File: Ctl5_O.mznld
 Description: Control, outer layer File:
 `InnerGroup_protein_quantification.csv` **Description:**\ Protein
 quantification in the inner layer group. **Variable List:** * Accession:
 UniProt/Swiss-Prot database identifier. * Peptide counts: The number of
 peptide sequences assigned to the corresponding protein. * Unique
 peptides: The number of unique peptide sequences among the peptides
 counted for the corresponding protein. * Confidence score: The protein
 confidence score is calculated as the sum of the identification scores of
 the assigned peptides. * Anova (p): The p-value obtained from a one-way
 analysis of variance (ANOVA). * q Value: Corrected p-value. * Max fold
 change: The fold change between the condition with the highest mean
 abundance and the condition with the lowest mean abundance. * Power:
 Statistical power for ANOVA. * Highest mean condition: The condition
 showing the highest mean protein abundance. * Lowest mean condition: The
 condition showing the lowest mean protein abundance. * Description: The
 protein name corresponding to the accession number. * Normalized
 abundance: The summed abundance of peptide-derived peaks used for protein
 quantification after normalization in the inner group. * Raw abundance:
 The total abundance of peptide-derived peaks used for protein
 quantification before normalization in the inner group. * Spectral counts:
 The total number of peptide spectral counts prior to normalization in the
 inner group. File: `MiddleGroup_protein_quantification.csv`
 **Description:**\ Protein quantification in the middle layer group.
 **Variable List:** * Accession: UniProt/Swiss-Prot database identifier. *
 Peptide counts: The number of peptide sequences assigned to the
 corresponding protein. * Unique peptides: The number of unique peptide
 sequences among the peptides counted for the corresponding protein. *
 Confidence score: The protein confidence score is calculated as the sum of
 the identification scores of the assigned peptides. * Anova (p): The
 p-value obtained from a one-way analysis of variance (ANOVA). * q Value:
 Corrected p-value. * Max fold change: The fold change between the
 condition with the highest mean abundance and the condition with the
 lowest mean abundance. * Power: Statistical power for ANOVA. * Highest
 mean condition: The condition showing the highest mean protein abundance.
 * Lowest mean condition: The condition showing the lowest mean protein
 abundance. * Description: The protein name corresponding to the accession
 number. * Normalized abundance: The summed abundance of peptide-derived
 peaks used for protein quantification after normalization in the middle
 group. * Raw abundance: The total abundance of peptide-derived peaks used
 for protein quantification before normalization in the middle group. *
 Spectral counts: The total number of peptide spectral counts prior to
 normalization in the middle group. File:
 `OuterGroup_protein_quantification.csv` **Description:**\ Protein
 quantification in the outer layer group. **Variable List:** * Accession:
 UniProt/Swiss-Prot database identifier. * Peptide counts: The number of
 peptide sequences assigned to the corresponding protein. * Unique
 peptides: The number of unique peptide sequences among the peptides
 counted for the corresponding protein. * Confidence score: The protein
 confidence score is calculated as the sum of the identification scores of
 the assigned peptides. * Anova (p): The p-value obtained from a one-way
 analysis of variance (ANOVA). * q Value: Corrected p-value. * Max fold
 change: The fold change between the condition with the highest mean
 abundance and the condition with the lowest mean abundance. * Power:
 Statistical power for ANOVA. * Highest mean condition: The condition
 showing the highest mean protein abundance. * Lowest mean condition: The
 condition showing the lowest mean protein abundance. * Description: The
 protein name corresponding to the accession number. * Normalized
 abundance: The summed abundance of peptide-derived peaks used for protein
 quantification after normalization in the outer group. * Raw abundance:
 The total abundance of peptide-derived peaks used for protein
 quantification before normalization in the outer group. * Spectral counts:
 The total number of peptide spectral counts prior to normalization in the
 outer group. ## Code/software The mass spectrometer was operated using
 Xcalibur software. Full-scan MS spectra were measured from 300 to 1,500
 m/z, and each of the 20 most abundant ions was subsequently subjected to
 HCD product ion scans. For protein and peptide identification, peak lists
 and exported mznld files were generated using Progenesis QI for
 proteomics.  We have also extracted the MS information from the mznld
 files and placed it in tabular data documents using Progenesis QI for
 proteomics. The data in Excel format is available in three CSV files. ##
 Human subjects data Written informed consent for the academic use of the
 tissue was obtained from the relatives of all decedents included in the
 study, and the study was approved by the institutional ethics committee
 (approval number: 21R177). This study was conducted in accordance with the
 ethical standards of the 1964 Declaration of Helsinki and its subsequent
 amendments.