Skip to main content
Erschienen in: Cardiovascular Drugs and Therapy 3/2015

01.06.2015 | REVIEW ARTICLE

Data Mining as a Powerful Tool for Creating Novel Drugs in Cardiovascular Medicine: The Importance of a “Back-and-Forth Loop” Between Clinical Data and Basic Research

verfasst von: Masafumi Kitakaze, Masanori Asakura, Atsushi Nakano, Seiji Takashima, Takashi Washio

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 3/2015

Einloggen, um Zugang zu erhalten

Abstract

Cardiovascular diseases, which lead to cardiovascular events including death, progress with many deleterious pathophysiological sequels. If a cause-and-effect relationship follows a one‐to‐one relation, we can focus on a cause to treat an effect, but such a relation cannot be applied in cardiovascular diseases. To identify novel drugs in the cardiovascular field, we generally adopt two different strategies: induction and deduction. In the cardiovascular field, it is difficult to use deduction because cardiovascular diseases are caused by many factors, leading us to use induction. In this method, we consider all clinical data, such as medical records or genetic data, and identify a few candidates. Recent computational and mathematical advances enable us to use data-mining methods to uncover hidden relationships between many parameters and clinical outcomes. However, because these candidates are not identified as promoting or inhibiting factors, or as causal or consequent factors of cardiovascular diseases, we need to test them in basic research, and bring them back to the clinical field to test their efficacy in clinical trials. With such a “back-and-forth loop” between clinical observation and basic research, data-mining methods may provide novel strategies leading to new tools for clinicians, basic findings for researchers, and better outcomes for patients.
Literatur
1.
Zurück zum Zitat Braunwald E, Bristow MR. Congestive heart failure: fifty years of progress. Circulation. 2000;102(20 Suppl 4):IV14–23.PubMed Braunwald E, Bristow MR. Congestive heart failure: fifty years of progress. Circulation. 2000;102(20 Suppl 4):IV14–23.PubMed
2.
Zurück zum Zitat Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63(12):1123–33.PubMedCrossRef Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63(12):1123–33.PubMedCrossRef
3.
Zurück zum Zitat Packer M. Neurohormonal interactions and adaptations in congestive heart failure. Circulation. 1988;77:721–30.PubMedCrossRef Packer M. Neurohormonal interactions and adaptations in congestive heart failure. Circulation. 1988;77:721–30.PubMedCrossRef
5.
Zurück zum Zitat Podgorelec V, Kokol P, Stiglic B, Rozman I. Decision trees: an overview and their use in medicine. Med Syst. 2002;26(5):445–63.CrossRef Podgorelec V, Kokol P, Stiglic B, Rozman I. Decision trees: an overview and their use in medicine. Med Syst. 2002;26(5):445–63.CrossRef
6.
Zurück zum Zitat Han J, Kamber M, Pei J. Data mining: concepts and techniques, Third Edition, The Morgan Kaufmann Series in Data Management Systems. Morgan Kaufmann, 2011. Han J, Kamber M, Pei J. Data mining: concepts and techniques, Third Edition, The Morgan Kaufmann Series in Data Management Systems. Morgan Kaufmann, 2011.
7.
Zurück zum Zitat Mardia KV, Kent JT, Bibby JM. Multivariate analysis, Probability and mathematical statistics. Academic Press, 1979. Mardia KV, Kent JT, Bibby JM. Multivariate analysis, Probability and mathematical statistics. Academic Press, 1979.
8.
Zurück zum Zitat Schoelkopf B, Smola AJ. Learning with Kernels: support vector machines, regularization, optimization, and beyond, adaptive computation and machine learning series. MIT Press, 2002. Schoelkopf B, Smola AJ. Learning with Kernels: support vector machines, regularization, optimization, and beyond, adaptive computation and machine learning series. MIT Press, 2002.
9.
Zurück zum Zitat Pearl J. Causality: models, reasoning, and inference, Second Edition. Cambridge University Press, 2009. Pearl J. Causality: models, reasoning, and inference, Second Edition. Cambridge University Press, 2009.
10.
Zurück zum Zitat Aggarwal CC, Reddy CK. Data clustering: algorithms and applications, Chapman & Hall/CRC data mining and knowledge discovery series. Chapman & Hall/CRC Press, 2013. Aggarwal CC, Reddy CK. Data clustering: algorithms and applications, Chapman & Hall/CRC data mining and knowledge discovery series. Chapman & Hall/CRC Press, 2013.
11.
Zurück zum Zitat Aggarwal CC, Han J. Frequent pattern mining. Springer, 2014. Aggarwal CC, Han J. Frequent pattern mining. Springer, 2014.
12.
Zurück zum Zitat Hodge V. Outlier and anomaly detection: a survey of outlier and anomaly detection methods. Lap Lambert Academic Publishing, 2011. Hodge V. Outlier and anomaly detection: a survey of outlier and anomaly detection methods. Lap Lambert Academic Publishing, 2011.
13.
14.
Zurück zum Zitat Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987;51(6):987–1000.PubMedCrossRef Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987;51(6):987–1000.PubMedCrossRef
15.
Zurück zum Zitat Lashkari DA, DeRisi JL, McCusker JH, Namath AF, Gentile C, Hwang SY, et al. Yeast microarrays for genome wide parallel genetic and gene expression analysis. Proc Natl Acad Sci U S A. 1997;94(24):13057–62.PubMedCentralPubMedCrossRef Lashkari DA, DeRisi JL, McCusker JH, Namath AF, Gentile C, Hwang SY, et al. Yeast microarrays for genome wide parallel genetic and gene expression analysis. Proc Natl Acad Sci U S A. 1997;94(24):13057–62.PubMedCentralPubMedCrossRef
16.
Zurück zum Zitat Seguchi O, Takashima S, Yamazaki S, Asakura M, Asano Y, Shintani Y, et al. A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart. J Clin Invest. 2007;117(10):2812–24.PubMedCentralPubMedCrossRef Seguchi O, Takashima S, Yamazaki S, Asakura M, Asano Y, Shintani Y, et al. A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart. J Clin Invest. 2007;117(10):2812–24.PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, et al. Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation. Proc Natl Acad Sci U S A. 2014;111(1):273–8.PubMedCentralPubMedCrossRef Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, et al. Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation. Proc Natl Acad Sci U S A. 2014;111(1):273–8.PubMedCentralPubMedCrossRef
18.
Zurück zum Zitat Fareed M, Afza MI. Single nucleotide polymorphism in genome-wide association of human population: a tool for broad spectrum service. Egyptian J Med Hum Genet. 2013;14:123–34.CrossRef Fareed M, Afza MI. Single nucleotide polymorphism in genome-wide association of human population: a tool for broad spectrum service. Egyptian J Med Hum Genet. 2013;14:123–34.CrossRef
19.
Zurück zum Zitat Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461(7261):252–6.CrossRef Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461(7261):252–6.CrossRef
20.
Zurück zum Zitat Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154–6.PubMedCrossRef Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154–6.PubMedCrossRef
21.
Zurück zum Zitat Steinberg D, Witztum JL. Inhibition of PCSK9: a powerful weapon for achieving ideal LDL cholesterol levels. Proc Natl Acad Sci U S A. 2009;106(24):9546–7.PubMedCentralPubMedCrossRef Steinberg D, Witztum JL. Inhibition of PCSK9: a powerful weapon for achieving ideal LDL cholesterol levels. Proc Natl Acad Sci U S A. 2009;106(24):9546–7.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet. 2014;383(9911):60–8.PubMedCentralPubMedCrossRef Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet. 2014;383(9911):60–8.PubMedCentralPubMedCrossRef
23.
Zurück zum Zitat Boch J. TALEs of genome targeting. Nature Biotechnol 29(2): 135–6. Boch J. TALEs of genome targeting. Nature Biotechnol 29(2): 135–6.
24.
25.
Zurück zum Zitat Kim J, Washio T, Yamagishi M, Yasumura Y, Nakatani S, Hashimura K, et al. A novel data mining approach to the identification of effective drugs or combinations for targeted endpoints-application to chronic heart failure as a New form of evidence-based medicine. Cardiovasc Drugs Ther. 2004;18:483–9.PubMedCrossRef Kim J, Washio T, Yamagishi M, Yasumura Y, Nakatani S, Hashimura K, et al. A novel data mining approach to the identification of effective drugs or combinations for targeted endpoints-application to chronic heart failure as a New form of evidence-based medicine. Cardiovasc Drugs Ther. 2004;18:483–9.PubMedCrossRef
26.
Zurück zum Zitat Hough LB. Genomics meets histamine receptors: new subtypes, new receptors. Mol Pharmacol. 2001;59:415–9.PubMed Hough LB. Genomics meets histamine receptors: new subtypes, new receptors. Mol Pharmacol. 2001;59:415–9.PubMed
27.
Zurück zum Zitat Leurs R, Bakker RA, Timmerman H, de Esch IJ. The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005;4:107–20.PubMedCrossRef Leurs R, Bakker RA, Timmerman H, de Esch IJ. The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005;4:107–20.PubMedCrossRef
28.
Zurück zum Zitat Gantz I, Schaffer M, DelValle J, Logsdon C, Campbell V, Uhler M, et al. Molecular cloning of a gene encoding the histamine H2 receptor. Proc Natl Acad Sci U S A. 1991;88:429–33.PubMedCentralPubMedCrossRef Gantz I, Schaffer M, DelValle J, Logsdon C, Campbell V, Uhler M, et al. Molecular cloning of a gene encoding the histamine H2 receptor. Proc Natl Acad Sci U S A. 1991;88:429–33.PubMedCentralPubMedCrossRef
29.
Zurück zum Zitat Matsuda N, Jesmin S, Takahashi Y, Hatta E, Kobayashi M, Matsuyama K, et al. Histamine H1 and H2 receptor gene and protein levels are differentially expressed in the hearts of rodents and humans. J Pharmacol Exp Ther. 2004;309:786–95.PubMedCrossRef Matsuda N, Jesmin S, Takahashi Y, Hatta E, Kobayashi M, Matsuyama K, et al. Histamine H1 and H2 receptor gene and protein levels are differentially expressed in the hearts of rodents and humans. J Pharmacol Exp Ther. 2004;309:786–95.PubMedCrossRef
30.
Zurück zum Zitat Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, et al. International union of pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev. 1997;49:253–78.PubMed Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, et al. International union of pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev. 1997;49:253–78.PubMed
31.
Zurück zum Zitat Eckel L, Gristwood RW, Nawrath H, Owen DA, Satter P. Inotropic and electrophysiological effects of histamine on human ventricular heart muscle. J Physiol. 1982;330:111–23.PubMedCentralPubMedCrossRef Eckel L, Gristwood RW, Nawrath H, Owen DA, Satter P. Inotropic and electrophysiological effects of histamine on human ventricular heart muscle. J Physiol. 1982;330:111–23.PubMedCentralPubMedCrossRef
32.
Zurück zum Zitat Du XY, Schoemaker RG, X462P6, Bos E, Saxena PR. Effects of histamine on porcine isolated myocardium: differentiation from effects on human tissue. J Cardiovasc Pharmacol 1993;22:468–73. Du XY, Schoemaker RG, X462P6, Bos E, Saxena PR. Effects of histamine on porcine isolated myocardium: differentiation from effects on human tissue. J Cardiovasc Pharmacol 1993;22:468–73.
33.
Zurück zum Zitat Hattori Y. Cardiac histamine receptors: their pharmacological consequences and signal transduction pathways. Methods Find Exp Clin Pharmacol. 1999;21:123–31.PubMedCrossRef Hattori Y. Cardiac histamine receptors: their pharmacological consequences and signal transduction pathways. Methods Find Exp Clin Pharmacol. 1999;21:123–31.PubMedCrossRef
34.
Zurück zum Zitat Kirch W, Halabi A, Hinrichsen H. Hemodynamic effects of quinidine and famotidine in patients with congestive heart failure. Clin Pharmacol Ther. 1992;51:325–33.PubMedCrossRef Kirch W, Halabi A, Hinrichsen H. Hemodynamic effects of quinidine and famotidine in patients with congestive heart failure. Clin Pharmacol Ther. 1992;51:325–33.PubMedCrossRef
35.
Zurück zum Zitat Maronle G. The role of mast cells in cardiovascular disease. In: Matsumori A, editor. Cardiomyopathies in heart failure: biomolecular, infectious and immune mechanisms. MA: Kluwer Academic Publishers; 2003. p. 185–228.CrossRef Maronle G. The role of mast cells in cardiovascular disease. In: Matsumori A, editor. Cardiomyopathies in heart failure: biomolecular, infectious and immune mechanisms. MA: Kluwer Academic Publishers; 2003. p. 185–228.CrossRef
36.
Zurück zum Zitat Asanuma H, Minamino T, Ogai A, Kim J, Asakura M, Komamura K, et al. Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs. J Mol Cell Cardiol. 2006;40(5):666–74.PubMedCrossRef Asanuma H, Minamino T, Ogai A, Kim J, Asakura M, Komamura K, et al. Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs. J Mol Cell Cardiol. 2006;40(5):666–74.PubMedCrossRef
37.
Zurück zum Zitat Zeng Z, Shen L, Li X, Luo T, Wei X, Zhang J, et al. Disruption of histamine H2 receptor slows heart failure progression through reducing myocardial apoptosis and fibrosis. Clin Sci (Lond). 2014;127(7):435–48.CrossRef Zeng Z, Shen L, Li X, Luo T, Wei X, Zhang J, et al. Disruption of histamine H2 receptor slows heart failure progression through reducing myocardial apoptosis and fibrosis. Clin Sci (Lond). 2014;127(7):435–48.CrossRef
38.
Zurück zum Zitat Takahama H, Asanuma H, Sanada S, Fujita M, Sasaki H, Wakeno M, et al. A histamine H2 receptor blocker ameliorates development of heart failure in dogs independently of β-adrenergic receptor blockade. Basic Res Cardiol. 2010;105(6):787–94.PubMedCrossRef Takahama H, Asanuma H, Sanada S, Fujita M, Sasaki H, Wakeno M, et al. A histamine H2 receptor blocker ameliorates development of heart failure in dogs independently of β-adrenergic receptor blockade. Basic Res Cardiol. 2010;105(6):787–94.PubMedCrossRef
39.
Zurück zum Zitat Kim J, Ogai A, Nakatani S, Hashimura K, Kanzaki H, Komamura K, et al. Impact of blockade of histamine H2 receptors on chronic heart failure revealed by retrospective and prospective randomized studies. J Am Coll Cardiol. 2006;48(7):1378–84.PubMedCrossRef Kim J, Ogai A, Nakatani S, Hashimura K, Kanzaki H, Komamura K, et al. Impact of blockade of histamine H2 receptors on chronic heart failure revealed by retrospective and prospective randomized studies. J Am Coll Cardiol. 2006;48(7):1378–84.PubMedCrossRef
40.
Zurück zum Zitat Liao Y, Takashima S, Zhao H, Asano Y, Shintani Y, Minamino T, et al. Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice. Cardiovasc Res. 2006;70(1):107–16.PubMedCrossRef Liao Y, Takashima S, Zhao H, Asano Y, Shintani Y, Minamino T, et al. Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice. Cardiovasc Res. 2006;70(1):107–16.PubMedCrossRef
41.
Zurück zum Zitat Sasaki H, Asanuma H, Fujita M, Takahama H, Wakeno M, Ito S, et al. Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase. Circulation. 2009;119(19):2568–77.PubMedCrossRef Sasaki H, Asanuma H, Fujita M, Takahama H, Wakeno M, Ito S, et al. Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase. Circulation. 2009;119(19):2568–77.PubMedCrossRef
42.
Zurück zum Zitat Kim J, Nakatani S, Hashimura K, Komamura K, Kanzaki H, Asakura M, et al. Abnormal glucose tolerance contributes to the progression of chronic heart failure in patients with dilated cardiomyopathy. Hypertens Res. 2006;29(10):775–82.PubMedCrossRef Kim J, Nakatani S, Hashimura K, Komamura K, Kanzaki H, Asakura M, et al. Abnormal glucose tolerance contributes to the progression of chronic heart failure in patients with dilated cardiomyopathy. Hypertens Res. 2006;29(10):775–82.PubMedCrossRef
43.
Zurück zum Zitat Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996;94:2807–16.PubMedCrossRef Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996;94:2807–16.PubMedCrossRef
44.
Zurück zum Zitat Wong M, Staszewsky L, Latini R, Barlera S, Volpi A, Chiang YT, et al. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol. 2002;40:970–5.PubMedCrossRef Wong M, Staszewsky L, Latini R, Barlera S, Volpi A, Chiang YT, et al. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol. 2002;40:970–5.PubMedCrossRef
45.
Zurück zum Zitat Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.PubMedCrossRef Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.PubMedCrossRef
Metadaten
Titel
Data Mining as a Powerful Tool for Creating Novel Drugs in Cardiovascular Medicine: The Importance of a “Back-and-Forth Loop” Between Clinical Data and Basic Research
verfasst von
Masafumi Kitakaze
Masanori Asakura
Atsushi Nakano
Seiji Takashima
Takashi Washio
Publikationsdatum
01.06.2015
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 3/2015
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-015-6602-9

Weitere Artikel der Ausgabe 3/2015

Cardiovascular Drugs and Therapy 3/2015 Zur Ausgabe

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

GLP-1-Agonisten können Fortschreiten diabetischer Retinopathie begünstigen

24.05.2024 Diabetische Retinopathie Nachrichten

Möglicherweise hängt es von der Art der Diabetesmedikamente ab, wie hoch das Risiko der Betroffenen ist, dass sich sehkraftgefährdende Komplikationen verschlimmern.

TAVI versus Klappenchirurgie: Neue Vergleichsstudie sorgt für Erstaunen

21.05.2024 TAVI Nachrichten

Bei schwerer Aortenstenose und obstruktiver KHK empfehlen die Leitlinien derzeit eine chirurgische Kombi-Behandlung aus Klappenersatz plus Bypass-OP. Diese Empfehlung wird allerdings jetzt durch eine aktuelle Studie infrage gestellt – mit überraschender Deutlichkeit.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.