A scheme for the analysis of microarray measurements based on a quantitative theoretical framework for bacterial cell growth: application to studies of Mycobacterium tuberculosis.

A theoretical framework was established for the interpretation of microarray measurements. Mathematical equations were derived that link the molecular processes involved in the transcription and translation of an open reading frame (ORF) with the properties of a population of cells. The theory was applied to three published sets of microarray measurements related to the growth of Mycobacterium tuberculosis. It was shown for strains growing at the same rate, for example wild-type and mutant strains, that the expression ratio obtained by microarray analysis for a particular ORF is equal to the ratio of the copy numbers of the encoded protein. The growth of M. tuberculosis in a batch culture was analysed at several time points over a period of 60 days. Several properties including the following were calculated for cells cultured for 60 days: mu<or=0.008 h(-1), there was a decrease in the number of ribosomes per cell to 26 % of the value at day 0, and only 40 % or less of this reduced number of ribosomes were estimated to be actively synthesizing protein. Profiles of the expression ratio observed for a particular ORF versus the period of cell culture were related to changes in the relative numbers of copies of the encoded protein per cell. Two profiles were found to have theoretical significance: profile I, exemplified by ORFs encoding proteins needed for DNA partition and DNA synthesis; and profile II, exemplified by ORFs encoding proteins (including ribosomal proteins) needed for protein synthesis. Data for a number of other genes including hspX, icl, dosR and ftsZ were also analysed.