At this time, I also want to discuss the two lectures by Dr. Dinu on methods in bioinformatics. As a molecular biologist, this is an area that has clearly evolved with enormous current and potential application. In 1981, using recombinant DNA tools that were just being developed, we were able to construct a cDNA library from rat liver. Subsequently, the plating of the cDNAs on to special large sheets of filter paper could be screened by sequential colony hybridization with cDNA probes from different hormonal treatments. This yielded different abundances for specific cDNA, reflective of specific mRNAs that were regulated by hormonal treatment. Abundance determination was visual following autoradiography, usually, Using digitization and quantitation schemes developed by NASA and Johns Hopkins, abundance determinations could be made for large numbers of colonies and compared and then represented by differing color intensity. Today, the use of microarrays with large libraries of DNA in combination with PCR amplification, is an offshoot of these earlier more labor intensive colony hybridizations for selection of relevant molecules to look for mechanisms of transcriptional regulation. One of the major advances has been the use of optically active molecules incorporated into probes rather than radioisotopes that have decay and health risks. The technology has also taken us much further in terms of the identification and quantitation of changes in mRNA abundance by the use of machine learning techniques with semi-supervised and supervised learning. This is particularly amazing for me and I look forward to applying these techniques.
Another aspect of extreme significance is the ability to use microarray for SNP analysis to look for disease association and potential gene abnormalities.These types of analyses provide a basis for the development of molecular techniques for disease identification and screening, and also potential evaluation of disease severity or recurrence (particularly in the case of cancer). I expect that this will evolve significantly and in no small part due to new techniques in proteomics. In the exercise for the class, I was very pleased to see the power of the gene software and Blast, that has in the past been principally manual and very clunky.
In my next BLOG, later this week, I will try to make some sense of Natural Language Processing and text retrieval, which has great potential for mining data on gene expression that is not immediately found on simple Pub Med searches.
Posted by Stuart
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