Genomics, proteomics and bioinformatics of human heart failure

C. G. Dos Remedios, C. C. Liew, P. D. Allen, Raimond Winslow, J. E. Van Eyk, M. J. Dunn

Research output: Contribution to journalArticle

Abstract

Unraveling the molecular complexities of human heart failure, particularly end-stage failure, can be achieved by combining multiple investigative approaches. There are several parts to the problem. Each patient is the product of a complex set of genetic variations, different degrees of influence of diets and lifestyles, and usually heart transplantation patients are treated with multiple drugs. The genomic status of the myocardium of any one transplant patient can be analysed using gene arrays (cDNA- or oligonucleotide-based) each with its own strengths and weaknesses. The proteins expressed by these failing hearts (myocardial proteomics) were first investigated over a decade ago using two-dimensional polyacrylamide gel electrophoresis (2DGE) which promised to resolve several thousand proteins in a single sample of failing heart. However, while 2DGE is very successful for the abundant and moderately expressed proteins, it struggles to identify proteins expressed at low levels. Highly focused first dimension separations combined with recent advances in mass spectrometry now provide new hope for solving this difficulty. Protein arrays are a more recent form of proteomics that hold great promise but, like the above methods, they have their own drawbacks. Our approach to solving the problems inherent in the genomics and proteomics of heart failure is to provide experts in each analytical method with a sample from the same human failing heart. This requires a sufficiently large number of samples from a sufficiently large pool of heart transplant patients as well as a large pool of non-diseased, non-failing human hearts. We have collected more than 200 hearts from patients undergoing heart transplantations and a further 50 non-failing hearts. By combining our expertise we expect to reduce and possibly eliminate the inherent difficulties of each analytical approach. Finally, we recognise the need for bioinformatics to make sense of the large quantities of data that will flow from our laboratories. Thus, we plan to provide meaningful molecular descriptions of a number of different conditions that result in terminal heart failure.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalJournal of Muscle Research and Cell Motility
Volume24
Issue number4-6
DOIs
StatePublished - 2003

Fingerprint

Bioinformatics
Genomics
Computational Biology
Proteomics
Heart Failure
Heart Transplantation
Oligonucleotide Array Sequence Analysis
Hope
Proteins
Transplants
Protein Array Analysis
Electrophoresis, Gel, Two-Dimensional
Life Style
Mass Spectrometry
Myocardium
Diet
Nutrition
Electrophoresis
Oligonucleotides
Mass spectrometry

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Dos Remedios, C. G., Liew, C. C., Allen, P. D., Winslow, R., Van Eyk, J. E., & Dunn, M. J. (2003). Genomics, proteomics and bioinformatics of human heart failure. Journal of Muscle Research and Cell Motility, 24(4-6), 251-260. https://doi.org/10.1023/A:1025433721505

Genomics, proteomics and bioinformatics of human heart failure. / Dos Remedios, C. G.; Liew, C. C.; Allen, P. D.; Winslow, Raimond; Van Eyk, J. E.; Dunn, M. J.

In: Journal of Muscle Research and Cell Motility, Vol. 24, No. 4-6, 2003, p. 251-260.

Research output: Contribution to journalArticle

Dos Remedios, CG, Liew, CC, Allen, PD, Winslow, R, Van Eyk, JE & Dunn, MJ 2003, 'Genomics, proteomics and bioinformatics of human heart failure', Journal of Muscle Research and Cell Motility, vol. 24, no. 4-6, pp. 251-260. https://doi.org/10.1023/A:1025433721505
Dos Remedios, C. G. ; Liew, C. C. ; Allen, P. D. ; Winslow, Raimond ; Van Eyk, J. E. ; Dunn, M. J. / Genomics, proteomics and bioinformatics of human heart failure. In: Journal of Muscle Research and Cell Motility. 2003 ; Vol. 24, No. 4-6. pp. 251-260.
@article{d82d1d00785b49e99a1c61e9486405cf,
title = "Genomics, proteomics and bioinformatics of human heart failure",
abstract = "Unraveling the molecular complexities of human heart failure, particularly end-stage failure, can be achieved by combining multiple investigative approaches. There are several parts to the problem. Each patient is the product of a complex set of genetic variations, different degrees of influence of diets and lifestyles, and usually heart transplantation patients are treated with multiple drugs. The genomic status of the myocardium of any one transplant patient can be analysed using gene arrays (cDNA- or oligonucleotide-based) each with its own strengths and weaknesses. The proteins expressed by these failing hearts (myocardial proteomics) were first investigated over a decade ago using two-dimensional polyacrylamide gel electrophoresis (2DGE) which promised to resolve several thousand proteins in a single sample of failing heart. However, while 2DGE is very successful for the abundant and moderately expressed proteins, it struggles to identify proteins expressed at low levels. Highly focused first dimension separations combined with recent advances in mass spectrometry now provide new hope for solving this difficulty. Protein arrays are a more recent form of proteomics that hold great promise but, like the above methods, they have their own drawbacks. Our approach to solving the problems inherent in the genomics and proteomics of heart failure is to provide experts in each analytical method with a sample from the same human failing heart. This requires a sufficiently large number of samples from a sufficiently large pool of heart transplant patients as well as a large pool of non-diseased, non-failing human hearts. We have collected more than 200 hearts from patients undergoing heart transplantations and a further 50 non-failing hearts. By combining our expertise we expect to reduce and possibly eliminate the inherent difficulties of each analytical approach. Finally, we recognise the need for bioinformatics to make sense of the large quantities of data that will flow from our laboratories. Thus, we plan to provide meaningful molecular descriptions of a number of different conditions that result in terminal heart failure.",
author = "{Dos Remedios}, {C. G.} and Liew, {C. C.} and Allen, {P. D.} and Raimond Winslow and {Van Eyk}, {J. E.} and Dunn, {M. J.}",
year = "2003",
doi = "10.1023/A:1025433721505",
language = "English (US)",
volume = "24",
pages = "251--260",
journal = "Journal of Muscle Research and Cell Motility",
issn = "0142-4319",
publisher = "Springer Netherlands",
number = "4-6",

}

TY - JOUR

T1 - Genomics, proteomics and bioinformatics of human heart failure

AU - Dos Remedios, C. G.

AU - Liew, C. C.

AU - Allen, P. D.

AU - Winslow, Raimond

AU - Van Eyk, J. E.

AU - Dunn, M. J.

PY - 2003

Y1 - 2003

N2 - Unraveling the molecular complexities of human heart failure, particularly end-stage failure, can be achieved by combining multiple investigative approaches. There are several parts to the problem. Each patient is the product of a complex set of genetic variations, different degrees of influence of diets and lifestyles, and usually heart transplantation patients are treated with multiple drugs. The genomic status of the myocardium of any one transplant patient can be analysed using gene arrays (cDNA- or oligonucleotide-based) each with its own strengths and weaknesses. The proteins expressed by these failing hearts (myocardial proteomics) were first investigated over a decade ago using two-dimensional polyacrylamide gel electrophoresis (2DGE) which promised to resolve several thousand proteins in a single sample of failing heart. However, while 2DGE is very successful for the abundant and moderately expressed proteins, it struggles to identify proteins expressed at low levels. Highly focused first dimension separations combined with recent advances in mass spectrometry now provide new hope for solving this difficulty. Protein arrays are a more recent form of proteomics that hold great promise but, like the above methods, they have their own drawbacks. Our approach to solving the problems inherent in the genomics and proteomics of heart failure is to provide experts in each analytical method with a sample from the same human failing heart. This requires a sufficiently large number of samples from a sufficiently large pool of heart transplant patients as well as a large pool of non-diseased, non-failing human hearts. We have collected more than 200 hearts from patients undergoing heart transplantations and a further 50 non-failing hearts. By combining our expertise we expect to reduce and possibly eliminate the inherent difficulties of each analytical approach. Finally, we recognise the need for bioinformatics to make sense of the large quantities of data that will flow from our laboratories. Thus, we plan to provide meaningful molecular descriptions of a number of different conditions that result in terminal heart failure.

AB - Unraveling the molecular complexities of human heart failure, particularly end-stage failure, can be achieved by combining multiple investigative approaches. There are several parts to the problem. Each patient is the product of a complex set of genetic variations, different degrees of influence of diets and lifestyles, and usually heart transplantation patients are treated with multiple drugs. The genomic status of the myocardium of any one transplant patient can be analysed using gene arrays (cDNA- or oligonucleotide-based) each with its own strengths and weaknesses. The proteins expressed by these failing hearts (myocardial proteomics) were first investigated over a decade ago using two-dimensional polyacrylamide gel electrophoresis (2DGE) which promised to resolve several thousand proteins in a single sample of failing heart. However, while 2DGE is very successful for the abundant and moderately expressed proteins, it struggles to identify proteins expressed at low levels. Highly focused first dimension separations combined with recent advances in mass spectrometry now provide new hope for solving this difficulty. Protein arrays are a more recent form of proteomics that hold great promise but, like the above methods, they have their own drawbacks. Our approach to solving the problems inherent in the genomics and proteomics of heart failure is to provide experts in each analytical method with a sample from the same human failing heart. This requires a sufficiently large number of samples from a sufficiently large pool of heart transplant patients as well as a large pool of non-diseased, non-failing human hearts. We have collected more than 200 hearts from patients undergoing heart transplantations and a further 50 non-failing hearts. By combining our expertise we expect to reduce and possibly eliminate the inherent difficulties of each analytical approach. Finally, we recognise the need for bioinformatics to make sense of the large quantities of data that will flow from our laboratories. Thus, we plan to provide meaningful molecular descriptions of a number of different conditions that result in terminal heart failure.

UR - http://www.scopus.com/inward/record.url?scp=0142156196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142156196&partnerID=8YFLogxK

U2 - 10.1023/A:1025433721505

DO - 10.1023/A:1025433721505

M3 - Article

C2 - 14620738

AN - SCOPUS:0142156196

VL - 24

SP - 251

EP - 260

JO - Journal of Muscle Research and Cell Motility

JF - Journal of Muscle Research and Cell Motility

SN - 0142-4319

IS - 4-6

ER -