We report the development of new tools and methods for facile integration and meaningful representation of high throughput data generated by genome-wide analyses of the model cyanobacterium Synechocystis PCC6803, for future genetic engineering aiming at increasing its level of hydrogen photoproduction. These robust tools comprise new oligonucleotide DNA microarrays to monitor the transcriptomic responses of all 3725 genes of Synechocystis, and the SVGMapping method and custom-made templates to represent the metabolic reprogramming for improved hydrogen production. We show, for the first time, that the AbrB2 repressor of the hydrogenase-encoding operon, also regulates metal transport and protection against oxidative stress, as well as numerous plasmid genes, which have been overlooked so far. This report will stimulate the construction and global analysis of hydrogen production mutants with the prospect of developing powerful cell factories for the sustainable production of hydrogen, as well as investigations of the probable role of plasmids in this process. Copyright (C) 2012, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.