Analysis and Visualization of Gene Expression Microarray Data in Human Cancer Using Self-Organizing Maps

cDNA microarrays permit massively parallel gene expression analysis and have spawned a new paradigm in the study of molecular biology. One of the significant challenges in this genomic revolution is to develop sophisticated approaches to facilitate the visualization, analysis, and interpretation of the vast amounts of multi-dimensional gene expression data. We have applied self-organizing map (SOM) in order to meet these challenges. In essence, we utilize U-matrix and component planes in microarray data visualization and introduce general procedure for assessing significance for a cluster detected from U-matrix. Our case studies consist of two data sets. First, we have analyzed a data set containing 13,824 genes in 14 breast cancer cell lines. In the second case we show an example of the SOM in drug treatment of prostate cancer cells. Our results indicate that (1) SOM is capable of helping finding certain biologically meaningful clusters, (2) clustering algorithms could be used for finding a set of potential predictor genes for classification purposes, and (3) comparison and visualization of the effects of different drugs is straightforward with the SOM. In summary, the SOM provides an excellent format for visualization and analysis of gene microarray data, and is likely to facilitate extraction of biologically and medically useful information.     

APTC-C-SA01: A Novel Bacteriophage Cocktail Targeting Staphylococcus aureus and MRSA Biofilms

The high infection and mortality rate of methicillin-resistant Staphylococcus aureus (MRSA) necessitates the urgent development of new treatment strategies. Bacteriophages (phages) have several advantages compared to antibiotics for the treatment of multi-drug-resistant bacterial infections, and thus provide a promising alternative to antibiotics. Here, S. aureus phages were isolated from patients and environmental sources. Phages were characterized for stability, morphology and genomic sequence and their bactericidal activity against the biofilm form of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA was investigated. Four S. aureus phages were isolated and tested against 51 MSSA and MRSA clinical isolates and reference strains. The phages had a broad host range of 82–94% individually and of >98% when combined and could significantly reduce the viability of S. aureus biofilms. The phages had a latent period of ≤20 min and burst size of >11 plaque forming units (PFU)/infected cell. Transmission electron microscopy (TEM) identified phages belonging to the family of Myoviridae. Genomic sequencing indicated the lytic nature of all four phages, with no identified resistance or virulence genes. The 4 phages showed a high complementarity with 49/51 strains (96%) sensitive to at least 2/4 phages tested. Furthermore, the frequency of bacteriophage insensitive mutant (BIM) generation was lower when the phages were combined into the phage cocktail APTC-C-SA01 than for bacteria exposed to each of the phages alone. In conclusion, APTC-C-SA01, containing four lytic S. aureus phages has the potential for further development as a treatment against MSSA and MRSA infections.