Abstract: A method for high-throughput analysis of genomic material originating from complex biological systems, including complex microbial systems and a method of detecting changes in a genomic material using restriction site tagged (RST) microarrays and sequence passporting technique (in particular microarrays containing NotI-clones). Using the present invention method, methylation or silencing of specific alleles, homozygous and hemizygous deletions, epigenetic factors, genetic predisposition, etc, information which is particularly useful in diagnosis and treatment of cancer diseases, can be detected. The RST microarrays and passporting can also be used for qualitative and quantitative analysis of complex microbial systems.