illuminating genomic dark matter via sfnr profiling

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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.

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Gene Profiling, Cancer Biology, SNP, SFNR Profiling.

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  • 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.