Personalized Medicine “It doesn't get more personal than this.”

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peopLe of the Book
Take the number of letters in 1,000 bibles, says
computer scientist Ron Shamir. That’s about the
number of “letters” – the 3 billion chemical bases –
making up each person’s total DNA.
However, only 2 percent of these letters spell out, or encode, the
20,000 or so genes in our bodies. How can scientists know which
sequence of letters translates into a working gene and which does not?
Moreover, how can they determine which gene variant or mutation is
responsible for diseases?
“This is where bioinformatics comes in – the point where biology
and computer science intersect,” says Prof. Shamir, who heads TAU’s
Edmond J. Safra Bioinformatics Program.
The field of bioinformatics emerged in the late 1980s and early 1990s
in response to the huge computational demands of the Human Genome
Project. Embracing the field early, Tel Aviv University has since produced
the largest group of bioinformatics specialists in Israel under the Edmond
J. Safra Program and ranks among the world’s leaders in the field.
“We’re coming up with new mathematical tools and software to analyze
the data,” elaborates Shamir, who is a faculty member of the Blavatnik
School of Computer Science at the Raymond and Beverly Sackler Faculty
of Exact Sciences. “And the data sets are just getting bigger as genome
sequencing becomes more widespread.”
One of the challenges is figuring out the genome’s rules. Researchers
must determine the sequence characteristics of the gene-coding regions
versus the non-coding regions, and develop algorithms to statistically
infer where the genes are. Complicating matters is the surprising fact that
human genes are not contiguous in the DNA sequence. They can be made
up of 5 to 30 unjoined segments.
“That’s a low-end problem,” notes Shamir. Suppose, he continues, that
the 20,000 human genes and their corresponding proteins are identified.
Yet in a living cell, all these proteins are co-existing and interacting, and
this is what makes the cell and the living organism function. “Knowing
what each gene does still doesn’t tell you the whole story,” Shamir says.
He offers another analogy to help understand the dimensions of the
problem. “If the genome is like an orchestra with 20,000 instruments,
knowing what the flute plays does not help you hear the score or know the
composition.”
The need to understand biology not just on the molecular level but as a
complex system has led to a new field – systems biology – which TAU has
been building up in recent years.
“Funding from the Edmond J. Safra Bioinformatics Program has
enabled us to recruit the best young researchers and nurture a strong
body of interdisciplinary students,” stresses Shamir. “Theoreticians
collaborate with experimentalists, campus groups with hospital clinicians.
The pace is break-neck. We have to be agile and quick.”
checked this network against tissue
samples from breast cancer patients to
isolate 9 genes that, under laboratory
conditions, reliably predicted MET risk.
Soon, hopes Tsarfaty, doctors will be
able to screen for the 9 telltale genes in
a biopsy, and to offer more timely and
accurate therapy based on each patient’s
genetic makeup.
Tsarfaty has also developed an imaging
technique at the Sackler Institute
for Molecular Medicine for showing
in a patient’s body, in real time, when
MET is active and, after targeted drug
therapy, inactive. “This will personalize
the care to the highest degree. We
will be able to actually see, as a live
image, if a certain drug is inhibiting
the MET or if we need to change the
medication,” he says.
Genetic component of drug
response
“The era of one medicine for everyone
is ending,” asserts SNP sleuth
Dr. Halperin. “The new paradigm will
involve doctors prescribing drugs according
to an individual’s genetics.”
Advancing this goal is extremely important,
given that in the United States
alone an estimated 2.2 million people
either fail to respond to medications or
experience serious reactions each year.
An additional 100,000 people die from
harmful effects.
At the TAU-affiliated Sheba Cancer
Research Center at Tel Hashomer
Hospital, TAU professor Gideon
Rechavi leads one of the best-known
groups in the world for identifying
genes involved in cancer drug response
and transferring this knowledge to the
clinic.
In one project, Prof. Rechavi’s group
is studying mutations that cause certain
patients with chronic myeloid leukemia,
a cancer of the white blood cells,
to develop resistance to a life-saving
drug. The scientists are developing a
genetic testing technique for finding out
quickly and accurately who has these