Distinct Myocardial Transcriptomic Profiles of Cardiomyopathies Stratified by the Mutant Genes
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patient Cohorts
2.2. Sample Preparation and Sequencing Reaction
2.3. Read Processing
2.4. Data Normalisation, Principal Component Analysis and Determination of Differentially Expressed Genes
2.5. K-Means Clustering
2.6. GO Term and Pathway Analysis
2.7. Prediction of Secreted Proteins, Regulatory Proteins and Potential Candidate Drug Targets
3. Results
3.1. GO Term and Pathway Analysis
3.2. Prediction of Secreted Proteins, Regulatory Proteins and Potential Candidate Drug Targets
4. Discussion
4.1. GO Term and Pathway Analysis
4.2. Prediction of Secreted Proteins, Regulatory Proteins and Potential Candidate Drug Targets
4.3. Limitations of the Study
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Teekakirikul, P.; Kelly, M.A.; Rehm, H.L.; Lakdawala, N.K.; Funke, B.H. Inherited cardiomyopathies: Molecular genetics and clinical genetic testing in the postgenomic era. J. Mol. Diagn. 2013, 15, 158–170. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hershberger, R.E.; Lindenfeld, J.; Mestroni, L.; Seidman, C.E.; Taylor, M.R.; Towbin, J.A. Genetic evaluation of cardiomyopathy-A heart failure society of America practice guideline. J. Card. Fail. 2009, 15, 83–97. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Watkins, H.; Ashrafian, H.; Redwood, C. Inherited cardiomyopathies. N. Engl. J. Med. 2011, 364, 1643–1656. [Google Scholar] [CrossRef] [PubMed]
- Bhonsale, A.; Groeneweg, J.A.; James, C.A.; Dooijes, D.; Tichnell, C.; Jongbloed, J.D.H.; Murray, B.; Riele, A.S.T.; Berg, M.P.V.D.; Bikker, H.; et al. Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers. Eur. Heart J. 2015, 36, 847–855. [Google Scholar] [CrossRef] [PubMed]
- Rijdt, W.P.T.; Jongbloed, J.D.; De Boer, R.A.; Thiene, G.; Basso, C.; Berg, M.P.V.D.; Van Tintelen, J.P. Clinical utility gene card for: Arrhythmogenic right ventricular cardiomyopathy (ARVC). Eur. J. Hum. Genet. 2013, 22, 293. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brodehl, A.; Ebbinghaus, H.; Deutsch, M.-A.; Gummert, J.; Gaertner, A.; Ratnavadivel, S.; Milting, H. Human induced pluripotent stem-cell-derived cardiomyocytes as models for genetic cardiomyopathies. Int. J. Mol. Sci. 2019, 20, 4381. [Google Scholar] [CrossRef] [Green Version]
- Yancy, C.W.; Jessup, M.; Bozkurt, B.; Butler, J.; Casey, D.E.; Drazner, M.H.; Fonarow, G.C.; Geraci, S.A.; Horwich, T.; Januzzi, J.L.; et al. 2013 ACCF/AHA guideline for the management of heart failure. J. Am. Coll. Cardiol. 2013, 62, e147–e239. [Google Scholar] [CrossRef] [Green Version]
- Charron, P.; Arad, M.; Arbustini, E.; Basso, C.; Bilinska, Z.; Elliott, P.; Helio, T.; Keren, A.; McKenna, W.J.; Monserrat, L.; et al. Genetic counselling and testing in cardiomyopathies: A position statement of the European Society of Cardiology Working Group on myocardial and pericardial diseases. Eur. Heart J. 2010, 31, 2715–2726. [Google Scholar] [CrossRef] [Green Version]
- Alraies, M.C.; Eckman, P.M. Adult heart transplant: Indications and outcomes. J. Thorac. Dis. 2014, 6, 1120–1128. [Google Scholar]
- Towbin, J.A. Inherited cardiomyopathies. Circ. J. 2014, CJ–14. [Google Scholar] [CrossRef] [Green Version]
- Morales, A.; Hershberger, R.E. Genetic evaluation of dilated cardiomyopathy. Curr. Cardiol. Rep. 2013, 15, 375. [Google Scholar] [CrossRef] [PubMed]
- Vatta, M.; Marcus, F.; Towbin, J.A. Arrhythmogenic right ventricular cardiomyopathy: A ‘final common pathway’ that defines clinical phenotype. Eur. Heart J. 2007, 28, 529–530. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pilichou, K.; Thiene, G.; Bauce, B.; Rigato, I.; Lazzarini, E.; Migliore, F.; Marra, M.P.; Rizzo, S.; Zorzi, A.; Daliento, L.; et al. Arrhythmogenic cardiomyopathy. Orphanet J. Rare Dis. 2016, 11, 1–17. [Google Scholar] [CrossRef] [PubMed]
- Elliott, P.M.; Anastasakis, A.; Asimaki, A.; Basso, C.; Bauce, B.; Brooke, M.A.; Calkins, H.; Corrado, D.; Duru, F.; Green, K.J.; et al. Definition and treatment of arrhythmogenic cardiomyopathy: An updated expert panel report. Eur. J. Heart Fail. 2019, 21, 955–964. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Austin, K.M.; Trembley, M.A.; Chandler, S.F.; Sanders, S.P.; Saffitz, J.E.; Abrams, D.J.; Pu, W.T. Molecular mechanisms of arrhythmogenic cardiomyopathy. Nat. Rev. Cardiol. 2019, 16, 519–537. [Google Scholar] [CrossRef]
- Corrado, D.; Basso, C.; Judge, D.P. Arrhythmogenic cardiomyopathy. Circ. Res. 2017, 121, 784–802. [Google Scholar] [CrossRef] [Green Version]
- Akdis, D.; Brunckhorst, C.; Duru, F.; Saguner, A.M. Arrhythmogenic cardiomyopathy: Electrical and structural phenotypes. Arrhythm. Electrophysiol. Rev. 2016, 5, 90–101. [Google Scholar] [CrossRef] [Green Version]
- Towbin, J.A.; McKenna, W.J.; Abrams, D.J.; Ackerman, M.J.; Calkins, H.; Darrieux, F.C.; Daubert, J.P.; De Chillou, C.; DePasquale, E.C.; Desai, M.Y.; et al. 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Hear. Rhythm. 2019, 16, e301–e372. [Google Scholar] [CrossRef] [Green Version]
- Begay, R.L.; Graw, S.L.; Sinagra, G.; Asimaki, A.; Rowland, T.J.; Slavov, D.B.; Gowan, K.; Jones, K.L.; Brun, F.; Merlo, M.; et al. Filamin C truncation mutations are associated with arrhythmogenic dilated cardiomyopathy and changes in the cell-cell adhesion structures. JACC: Clin. Electrophysiol. 2018, 4, 504–514. [Google Scholar] [CrossRef]
- Cipriani, A.; Bauce, B.; De Lazzari, M.; Rigato, I.; Bariani, R.; Meneghin, S.; Pilichou, K.; Motta, R.; Aliberti, C.; Thiene, G.; et al. Arrhythmogenic right ventricular cardiomyopathy: Characterization of left ventricular phenotype and differential diagnosis with dilated cardiomyopathy. J. Am. Heart Assoc. 2020, 9, e014628. [Google Scholar] [CrossRef]
- Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier-Foster, J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015, 17, 405–423. [Google Scholar] [CrossRef] [PubMed]
- Corrado, D.; Basso, C.; Nava, A.; Thiene, G. Arrhythmogenic right ventricular cardiomyopathy: Current diagnostic and management strategies. Cardiol. Rev. 2001, 9, 259–265. [Google Scholar] [CrossRef] [PubMed]
- Pinto, Y.M.; Elliott, P.M.; Arbustini, E.; Adler, Y.; Anastasakis, A.; Böhm, M.; Duboc, D.; Gimeno, J.; De Groote, P.; Imazio, M.; et al. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: A position statement of the ESC working group on myocardial and pericardial diseases. Eur. Heart J. 2016, 37, 1850–1858. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Elliott, P.; Andersson, B.; Arbustini, E.; Bilinska, Z.; Cecchi, F.; Charron, P.; Dubourg, O.; Kühl, U.; Maisch, B.; McKenna, W.J.; et al. Classification of the cardiomyopathies: A position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur. Heart J. 2007, 29, 270–276. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marcus, F.I.; McKenna, W.J.; Sherrill, D.L.; Basso, C.; Bauce, B.; Bluemke, D.A.; Calkins, H.; Corrado, D.; Cox, M.G.; Daubert, J.P.; et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: Proposed modification of the task force criteria. Eur. Heart J. 2010, 31, 806–814. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jefferson, A.L.; Himali, J.J.; Beiser, A.S.; Au, R.; Massaro, J.M.; Seshadri, S.; Gona, P.; Salton, C.J.; DeCarli, C.; O’Donnell, C.J.; et al. Cardiac index is associated with brain aging. Circulation 2010, 122, 690–697. [Google Scholar] [CrossRef] [Green Version]
- Chen, S.; Huang, T.; Wen, T.; Li, H.; Xu, M.; Gu, J. MutScan: Fast detection and visualization of target mutations by scanning FASTQ data. BMC Bioinform. 2018, 19, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Bolger, A.M.; Lohse, M.; Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 2014, 30, 2114–2120. [Google Scholar] [CrossRef] [Green Version]
- Andrews, S. FastQC: A Quality Control. Tool for High. Throughout Sequence Data; Babraham Institute: Babraham, UK, 2010. [Google Scholar]
- Dobin, A.; Davis, C.A.; Schlesinger, F.; Drenkow, J.; Zaleski, C.; Jha, S.; Batut, P.; Chaisson, M.; Gingeras, T.R. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 2013, 29, 15–21. [Google Scholar] [CrossRef]
- Liao, Y.; Smyth, G.C.; Shi, W. FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2013, 30, 923–930. [Google Scholar] [CrossRef] [Green Version]
- Lun, A.T.L.; McCarthy, D.J.; Marioni, J.C. A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor. F1000Research 2016, 5, 2122. [Google Scholar] [CrossRef] [PubMed]
- Love, M.I.; Huber, W.; Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014, 15, 550. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wickham, H. ggplot2. Wiley Interdiscip. Rev. Comput. Stat. 2011, 3, 180–185. [Google Scholar] [CrossRef]
- Chen, H.; Boutros, P.C. VennDiagram: A package for the generation of highly-customizable Venn and Euler diagrams in R. BMC Bioinform. 2011, 12, 35. [Google Scholar] [CrossRef] [Green Version]
- Abu-Jamous, B.; Kelly, S. Clust: Automatic extraction of optimal co-expressed gene clusters from gene expression data. Genome Biol. 2018, 19, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Luo, W.; Friedman, M.S.; Shedden, K.; Hankenson, K.D.; Woolf, P.J. GAGE: Generally applicable gene set enrichment for pathway analysis. BMC Bioinform. 2009, 10, 161. [Google Scholar] [CrossRef] [Green Version]
- Turner, S. Tutorial: RNA-seq differential expression & pathway analysis with Sailfish, DESeq2, GAGE, and Pathview. DIM 2015, 16755, 6. [Google Scholar]
- Pages, H.; Carlson, M.; Falcon, S.; Li, N.A.; AnnotationDbi, P.; SQLForge, P. Annotation Database Interface; In R Package Version 1.52.0. Available online: https://bioconductor.org/packages/AnnotationDbi (accessed on 27 November 2020).
- Carlson, M.; Falcon, S.; Pages, H.; Li, N. Org. Hs. Eg. Db: Genome Wide Annotation for Human. In R Package Version 3.7.0; Springer: New York, NY, USA, 2018. [Google Scholar]
- Luo, W.; Brouwer, C. Pathview: An R/Bioconductor package for pathway-based data integration and visualization. Bioinformatics 2013, 29, 1830–1831. [Google Scholar] [CrossRef] [Green Version]
- Plotly Technologies Inc. Collaborative Data Science. Available online: https://plot.ly (accessed on 27 November 2020).
- Finan, C.; Gaulton, A.; Kruger, F.A.; Lumbers, R.T.; Shah, T.; Engmann, J.; Galver, L.; Kelley, R.; Karlsson, A.; Santos, R.; et al. The druggable genome and support for target identification and validation in drug development. Sci. Transl. Med. 2017, 9, eaag1166. [Google Scholar] [CrossRef]
- Hopkins, A.L.; Groom, C.R. The druggable genome. Nat. Rev. Drug Discov. 2002, 1, 727–730. [Google Scholar] [CrossRef]
- Brayson, D.; Frustaci, A.; Verardo, R.; Chimenti, C.; Russo, M.A.; Hayward, R.; Ahmad, S.M.; Vizcay-Barrena, G.; Protti, A.; Zammit, P.S.; et al. Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies. JCI Insight 2019, 4, 4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gaertner, A.; Schwientek, P.; Ellinghaus, P.; Summer, H.; Golz, S.; Kassner, A.; Schulz, U.; Gummert, J.; Milting, H. Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy. Physiol. Genom. 2012, 44, 99–109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klauke, B.; Gaertner-Rommel, A.; Schulz, U.; Kassner, A.; Zu Knyphausen, E.; Laser, T.; Kececioglu, D.; Paluszkiewicz, L.; Blanz, U.; Sandica, E.; et al. High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2-gene mutation. PLoS ONE 2017, 12, e0189489. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Van Der Zwaag, P.A.; Van Rijsingen, I.A.; Asimaki, A.; Jongbloed, J.D.; Van Veldhuisen, D.J.; Wiesfeld, A.C.; Cox, M.G.; Van Lochem, L.T.; De Boer, R.A.; Hofstra, R.M.; et al. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: Evidence supporting the concept of arrhythmogenic cardiomyopathy. Eur. J. Heart Fail. 2012, 14, 1199–1207. [Google Scholar] [CrossRef]
- Graziano, S.; Kreienkamp, R.; Coll-Bonfill, N.; Gonzalo, S. Causes and consequences of genomic instability in laminopathies: Replication stress and interferon response. Nucleus 2018, 9, 289–306. [Google Scholar] [CrossRef] [Green Version]
- Casademont, J.; Miró, Ò. Electron transport chain defects in heart failure. Heart Fail. Rev. 2002, 7, 131–139. [Google Scholar] [CrossRef]
- Bornstein, B.; Huertas, R.; Ochoa, P.; Campos, Y.; Guillen, F.; Garesse, R.; Arenas, J. Mitochondrial gene expression and respiratory enzyme activities in cardiac diseases. Biochim. Biophys. Acta (BBA)-Bioenergy 1998, 1406, 85–90. [Google Scholar] [CrossRef]
- Garrod, D.R.; Chidgey, M.A. Desmosome structure, composition and function. Biochim. Biophys. Acta (BBA)-Biomembr. 2008, 1778, 572–587. [Google Scholar] [CrossRef]
- Hall, C.L.; Gurha, P.; Sabater-Molina, M.; Asimaki, A.; Futema, M.; Lovering, R.C.; Suárez, M.P.; Aguilera, B.; Molina, P.; Zorio, E.; et al. RNA sequencing-based transcriptome profiling of cardiac tissue implicates novel putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy. Int. J. Cardiol. 2020, 302, 124–130. [Google Scholar] [CrossRef] [Green Version]
- Brodehl, A.; Rezazadeh, S.; Williams, T.; Munsie, N.M.; Liedtke, D.; Oh, T.; Ferrier, R.; Shen, Y.; Jones, S.J.M.; Stiegler, A.L.; et al. Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy. Transl. Res. 2019, 208, 15–29. [Google Scholar] [CrossRef]
- Patel, D.M.; Green, K.J. Desmosomes in the heart: A review of clinical and mechanistic analyses. Cell Commun. Adhes. 2014, 21, 109–128. [Google Scholar] [CrossRef] [PubMed]
- Winter, C.R.; Baker, R.C. L-glutamate-induced changes in intracellular calcium oscillation frequency through non-classical glutamate receptor binding in cultured rat myocardial cells. Life Sci. 1995, 57, 1925–1934. [Google Scholar] [CrossRef]
- Beqqali, A.; Bollen, I.A.; Rasmussen, T.B.; Hoogenhof, M.M.V.D.; Van Deutekom, H.W.; Schafer, S.; Haas, J.; Meder, B.; Sørensen, K.E.; Van Oort, R.J.; et al. A mutation in the glutamate-rich region of RNA-binding motif protein 20 causes dilated cardiomyopathy through missplicing of titin and impaired Frank-Starling mechanism. Cardiovasc. Res. 2016, 112, 452–463. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vikhorev, P.G.; Smoktunowicz, N.; Munster, A.B.; Copeland, O.; Kostin, S.; Montgiraud, C.; Messer, A.E.; Toliat, M.R.; Natalia, S.; Dos Remedios, C.G.; et al. Abnormal contractility in human heart myofibrils from patients with dilated cardiomyopathy due to mutations in TTN and contractile protein genes. Sci. Rep. 2017, 7, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Hinson, J.T.; Chopra, A.K.; Nafissi, N.; Polacheck, W.J.; Benson, C.C.; Swist, S.; Gorham, J.M.; Yang, L.; Schafer, S.; Sheng, C.C.; et al. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy. Science 2015, 349, 982–986. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ware, J.S.; Cook, S.A. Role of titin in cardiomyopathy: From DNA variants to patient stratification. Nat. Rev. Cardiol. 2017, 15, 241–252. [Google Scholar] [CrossRef]
- Cermakova, P.; Eriksdotter, M.; Lund, L.H.; Winblad, B.; Religa, P.; Religa, D. Heart failure and Alzheimer′s disease. J. Intern. Med. 2014, 277, 406–425. [Google Scholar] [CrossRef] [Green Version]
- Bujak, M.; Frangogiannis, N.G. The role of TGF-β; signaling in myocardial infarction and cardiac remodeling. Cardiovasc. Res. 2007, 74, 184–195. [Google Scholar] [CrossRef] [Green Version]
- Beffagna, G.; Occhi, G.; Nava, A.; Vitiello, L.; Ditadi, A.; Basso, C.; Bauce, B.; Carraro, G.; Thiene, G.; Towbin, J.A.; et al. Regulatory mutations in transforming growth factor-β3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc. Res. 2005, 65, 366–373. [Google Scholar] [CrossRef] [Green Version]
- Li, Q.; Lai, L. Prediction of potential drug targets based on simple sequence properties. BMC Bioinform. 2007, 8, 353. [Google Scholar] [CrossRef] [Green Version]
- Bowles, N.E.; Bowles, K.R.; Towbin, J.A. The “Final Common Pathway” hypothesis and inherited cardiovascular disease the role of Cytoskeletal proteins in dilated cardiomyopathy. Herz 2000, 25, 168–175. [Google Scholar] [CrossRef] [PubMed]
- Sweet, M.E.; Cocciolo, A.; Slavov, D.; Jones, K.L.; Sweet, J.R.; Graw, S.L.; Reece, T.B.; Ambardekar, A.V.; Bristow, M.R.; Mestroni, L.; et al. Transcriptome analysis of human heart failure reveals dysregulated cell adhesion in dilated cardiomyopathy and activated immune pathways in ischemic heart failure. BMC Genom. 2018, 19, 1–14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
LMNA (N = 6) | RBM20 (N = 4) | TTN (N = 9) | PKP2 (N = 6) | Significance (p-Value; ANOVA) | |
---|---|---|---|---|---|
age | 51 ± 10 | 38 ± 14 | 50 ± 15 | 53 ± 13 | 0.3037 * |
gender (m:f) | 2:4 | 4:0 | 7:2 | 5:1 | - |
CI (L/min/m2) | 1.66 ± 0.46 | 2.00 ± 0.41 | 2.27 ± 0.56 | 1.85 ± 0.49 | 0.1663 * |
LV-EF (%) | 23.3 ± 4.7 | 26.5 ± 10.5 | 23.9 ± 4.3 | 52.5 ± 15.4 | 2.4 × 10−5 * |
LVEDD (mm) | 60.5 ± 3.6 | 71.5 ± 7.0 | 68.3 ± 6.8 | 46 ± 9.7 | 1.9 × 10−5 * |
LVESD (mm) | 52.7 ± 4.3 | 64.8 ± 6.3 | 61 ± 9.5 | 34.5 ± 13.0 | 7.5 × 10−5 * |
FS (%) | 12.7 ± 3.6 | 9.3 ± 3.9 | 8.3 ± 2.3 | 26.3 ± 11.6 | 2.4 × 10−4 * |
disease | DCM | DCM | DCM | ARVC 1 | - |
treatment (HTx:LVAD-IP) | 6:0 | 3:1 | 8:1 | 6:0 | - |
ICD | 6/6 | 4/4 | 6/9 | 4/6 | - |
CAD | 0 | 1/4 | 0 | 0 | - |
Sample Type | Predicted Regulatory Proteins | Predicted Secretory Proteins | ||||
---|---|---|---|---|---|---|
Gene Name | padj | log2FC | Gene Name | padj | log2FC | |
LMNA | ZNF117 NKX2-5 FOXO1 RUNX2 TBX3 BCL11B ZFHX4 IKZF3 ZFHX3 LEF1 NHLH2 TFCP2L1 ONECUT2 RORC ZNF165 EOMES | 5.02 × 10−11 1.78 × 10−8 2.77 × 10−6 9.06 × 10−6 0.000258 0.000397 0.000619 0.000736 0.001378 0.002262 0.004392 0.004813 0.005433 0.005826 0.007406 0.009681 | 1.103 −1.069 1.172 1.631 −1.028 2.578 1.370 2.257 1.053 1.628 4.256 1.439 2.020 −1.136 −1.197 2.535 | MYL1 OSTN LEP NPFFR2 HTRA4 GRIA2 DPEP2 CNDP1 COL20A1 PIANP | 0.000208 0.000791 0.000820 0.002066 0.004334 0.008678 0.022995 0.026027 0.036507 0.041499 | 2.982 3.258 5.106 2.671 2.028 2.616 1.925 2.002 2.196 2.189 |
PKP2 | HHEX MEOX1 HLF BCL3 ARID5A FOXS1 HOPX PITX3 | 0.000275 0.000871 0.000889 0.000923 0.002452 0.005327 0.006332 0.006866 | −1.556 −1.464 1.142 −1.168 −1.087 −1.440 −3.044 1.960 | GABRG3 | 0.043429 | 2.024 |
RBM20 | ZNF827 PITX2 TSC22D2 ALX4 IRF7 SOX30 BACH2 MYC NR2F1 CEBPD GATA5 | 8.12 × 10−8 1.53 × 10−5 3.95 × 10−5 0.000567 0.000808 0.002415 0.002869 0.004139 0.004371 0.005437 0.007913 | 1.127 5.766 1.002 −1.949 −1.040 1.353 1.023 −1.138 3.039 −1.041 2.265 | WFDC3 | 0.038394 | 2.028 |
TTN | ZNF676 SREBF1 FOXK1 TCF7L1 HESX1 POU6F2 MYF6 BHLHE40 BHLHE22 | 5.47 × 10−5 9.02 × 10−5 0.000394 0.001645 0.004402 0.007423 0.009001 0.009302 0.009983 | 1.0369 −1.148 1.060 1.044 1.335 1.426 −3.230 −1.137 −1.462 | UPK3B MUC3A | 0.012358 0.047826 | 2.334 1.841 |
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Sielemann, K.; Elbeck, Z.; Gärtner, A.; Brodehl, A.; Stanasiuk, C.; Fox, H.; Paluszkiewicz, L.; Tiesmeier, J.; Wlost, S.; Gummert, J.; et al. Distinct Myocardial Transcriptomic Profiles of Cardiomyopathies Stratified by the Mutant Genes. Genes 2020, 11, 1430. https://doi.org/10.3390/genes11121430
Sielemann K, Elbeck Z, Gärtner A, Brodehl A, Stanasiuk C, Fox H, Paluszkiewicz L, Tiesmeier J, Wlost S, Gummert J, et al. Distinct Myocardial Transcriptomic Profiles of Cardiomyopathies Stratified by the Mutant Genes. Genes. 2020; 11(12):1430. https://doi.org/10.3390/genes11121430
Chicago/Turabian StyleSielemann, Katharina, Zaher Elbeck, Anna Gärtner, Andreas Brodehl, Caroline Stanasiuk, Henrik Fox, Lech Paluszkiewicz, Jens Tiesmeier, Stefan Wlost, Jan Gummert, and et al. 2020. "Distinct Myocardial Transcriptomic Profiles of Cardiomyopathies Stratified by the Mutant Genes" Genes 11, no. 12: 1430. https://doi.org/10.3390/genes11121430