illuminating genomic dark matter via sfnr profiling
DESCRIPTION
Gene Profiling, Cancer Biology, SNP, SFNR Profiling.TRANSCRIPT
-
Executive Summary: The traditional biological paradigm teaches that much of the human genome is
made up of Junk DNA, as it does not code directly for proteins. However, in the last decade, a
torrent of new research has emerged stressing the importance of non-coding regions of the genome as
important culprits of disease progression. In the light of these discoveries, clinicians are searching for
new tools to adequately grasp the growing complexity of the regulatory network involved with major
disease states, most notably cancer. The most famous, and potentially useful of these tools comes in
the form of genome profiling, that is, recording which regions of the genome are expressed in certain
biological maladies. This project took a new stance on profiling, by instead trying to profile the
transcriptome, the entirety of the transcribed, though not necessarily protein coding regions of the
genome. Status quo profiling technologies cannot perform this profiling function in a cost-effective
manner, nor can they record the expression of thousands of transcripts at the same time. In this
experiment, a new model of profiling, termed SNP-Flagged Non-Coding RNA Profiling, was
validated and tested for biological relevance. This model makes use of the biological fact that many of
these important non-coding RNAs lie over regions of the genome called Single Nucleotide
Polymorphisms, single-base pair changes in the genome found in DNA. Methods already exist to
profile SNPs, called microarrays. This project validated the theoretical ability to use SNPs to flag
non-coding RNA by mapping the association between the increase in the SNP copy numbers and the
increase in RNA transcription, which was found to be directly correlative. Afterwards, the SFNR
Profiling method was used to discriminate between different phenotypes of cancer cells, specifically,
those cells, which expressed Estrogen Receptor protein on their cell surfaces and those which did not,
as well as Basal cancer cells as compared to Luminal cells. This method was able to successfully
classify different types of cancer cells based on which SFNR molecules each type of cell expressed,
and therefore, this method can be used to effectively aid in clinical diagnostics and prognostics.