Works with Variety of Organisms
Oryzon Genomics has been active in analyzing gene expression levels, splice variants, and copy number variations in a wide array of organisms, ranging from yeast and rice, to rodents. These efforts also allowed Dr. Maes’ group to develop their flagship drug discovery program on cancer and neurodegenerative disease.
According to Dr. Maes, the only method to ascertain Alzheimer’s disease was through the use of post-mortem histological analysis, with gene expression often considered as the major obstacle because of time-sensitive capturing of gene expression patterns during autopsy.
At the same time, comparative analysis of brains of Alzheimer’s disease patients and controls still presented subtle differences, thus further increasing their need to identify a more sensitive and reliable approach for gene expression profiling. In the case of cancer, “Our prototype technology allowed us to identify essential regulators of leukemia stem cell potential, possibly for the treatment of acute myeloid leukemia (AML), especially of genetically defined subtypes of AMLs carrying an MLL translocation,” Dr. Maes added.
In the department of genetics at the Washington University School of Medicine, Anne M. Bowcock, Ph.D., professor, applied deep sequencing techniques in identifying major modifications in the changes in mRNA expression profiles of psoriasis patients. Instead of concentrating on exons and mRNA for analysis, Dr. Bowcock screened miRNAs for changes in gene expression, including modifications in miRNA editing.
The advantage of using miRNAs in gene expression profiling in specific diseases involves the capacity to identify noncoding genomic sequences, which have lately been implicated in disease progression and diagnostics. In the case of skin differentiation, miRNA gene expression analysis could “reveal dramatic changes in global microRNA expression, reflecting defects in keratinocytes, immune cells, and vasculature,” according to Dr. Bowcock.
Her research program on temporal regulation of miRNAs was conducted using digital gene expression analysis, allowing her team to perform a global screen of 67 human skin samples, resulting in the detection of close to 100 novel miRNA molecules that were differentially expressed in psoriatic skin. Her group ensured that the digital read counts were highly reproducible and statistically robust.
In addition, results validation was also performed using quantitative RT-PCR on the same skin samples, further strengthening the signature phenotype of diseased skin and elucidating the expression of marker proteins in skin lesions.