Integrative models of the heart: Achievements and limitations

The recently completed draft sequence of the human genome provides access to a vast database of information, containing of the order of 30 000-40 000 genes. These are understood to encode some 250 000 proteins. Understanding how the information in the genome is used to create this 'proteome' is a major challenge, not least because predicting the functionally important three-dimensional structure of proteins from their amino-acid sequences is very difficult. But even these formidable challenges pale into insignificance when we consider the complexity of the next stage: understanding the interactions of tens of thousands of proteins as they generate biological function. This is the task of quantitative analysis of physiological function, which in its entirety is now referred to as the 'physiome'. Bioinformatics and computational cell and organ modelling will play an increasingly important role in all these stages of unravelling the way in which the information contained in the genome is 'computed' to create living systems. Here, we address all but a small fragment of the physiome project: the development of integrative models of the heart.