Personalized Medicine - Translational Informatics: Realizing the Promise of Knowledge-Driven Healthcare - page 32

enabled have triggered a paradigm shift in biological inquiry. Instead of focusing
solely on one gene or protein of interest, technologies developed over the past few
decades have enabled collection of data across tens of thousands of molecules at a
time. In this way, biology has become more of a systems-oriented, data-driven dis-
cipline. In addition, increasing adoption of health information technology in the
form of electronic medical records, enables a learning health care system in which
information collected through clinical care, at different points in time and by differ-
ent providers, can be more easily consolidated and retrieved for use in both aggre-
gated analysis and clinical decision making. Increased information about an
individual, increased access to that information at the point of care, and more pre-
cisely targeted guidelines help to enable delivery of the right treatment to the right
patient, at the right time.

3.2 Not Your High School Teacher's Biology

3.2.1 Refresher: The Central Dogma of Biology

In order to give context to the sections below, what follows is a brief refresher in the
basics of molecular biology. Recall that DNA (deoxy-ribonucleic acid) exists as a
double helix in the nucleus of the cell. Its shape is often compared to a ladder,
though it might be better compared to a spiral staircase in which the steps are made
up of pairs of molecules known as nucleotides or “bases,” specifi cally, cytosine (C),
guanine (G), adenine (A), and thymine (T). A small portion of the genome, on the
order of 1.5 %, is devoted to the specifi cation of protein sequences [ 1 ], while the
vast majority of human DNA does not code for proteins. Of the remaining 98.5 %,
some is known to be structural, e.g. ribosomal RNA, which makes up part of the
ribosome, and some is used for gene regulation. For much of it, though, the function
remains unknown. The ENCODE project is a large NIH-funded initiative intended
to decipher the purpose and function of the rest of the genome, beyond the protein
coding segments. While it has long been suspected that use of the term “junk DNA”
for the remaining 98.5 % was a misnomer, the ENCODE consortium surprised
many researchers with the assertion that they had identifi ed biochemical functions
for over 80 % of the genome.
DNA has the property that specifi c bases only pair with specifi c other bases,
specifi cally G with C, and A with T (see Fig. 3.1 ). This leads to the ability for a
single strand of DNA to be used as a template to create a matching (complementary)
copy, which can in turn be used to create an exact copy of the initial sequence. This
template-based replication is what takes place when cells divide, creating two new
cells with the same genome as the original cell. This property can also be exploited
for a number of other purposes, from amplifying DNA (i.e. making many copies
of a specifi c DNA molecule), to capturing and identifying DNA, to its use as a
“barcode” to identify different species of organisms.