Hello.

I hope you enjoyed the field trip to

Kanigsberg and now
the time has come to look into algorithmic
ideas behind genome sequencing.
We have a lot of territory to cover, but
the good
news is that we will be joined today by
Dr. Son Pham,
one of the leading experts on genome
sequencing.
I wanted to start from a question.
Who are those people,
who look like criminal on mug shots?
And why they appear on the
same slide with three great mathematicians
from three different centuries?
By the end of this lesson, you will learn
the answer to this question, but some of
you have already guessed that we are
interested in
these people because we are interested in
their genes.
You can think about the human
genome as a 3 billion nucleotide long
book, written in A C G T alphabet.
And some of you may think that since human
are
so involved, then the genome must be the
longest genome known.
This is not true.
There are are genomes that are hundreds
time longer than the human genome.
As we speak, there are thousands of genome
sequencing
projects that is being conducted all over
the world.
Biologists are interested in genome
sequencing because they
can learn a lot from studying the genome.
For example, they can understand the
function of a human gene
by studying a similar gene in fly or even
in bacteria.
And of course there are numerous
applications of genome sequencing in
medicine,
agriculture, biotechnology, and many other
fields.
Genome sequencing started in 1977 when
Walter
Gilbert and Frederick Sanger invented the
first DNA sequencing technologies.
Usually great discoveries wait for two to
three
decades before they are awarded the Nobel
Prize.
In this case, the

Nobel committee waited just three years

before it
awarded the Nobel Prize to Sanger and
Gilbert.
It was obvious that this discovery will
have enormous implication for science.
However as great as this discovery was
sequencing technology invented by
Sanger and Gilbert was very expensive.
It would cost $3 billion to
sequence the human genome with this
technology, it didn't stop biologists,
who in 1990 started Human Genome Project
that is
still up to this day the largest
collaborative research project in biology.
The goal of this project was to sequence
human genome in
15 years and to deliver to the public by
the year 2005.
In 1997 there was an unexpected entry into
human genome sequencing progress.
Craig Venter founded a private company,
Solara Genomics, with the stated goal
to sequence the human genome ahead of
public Human Genome Project.
And this was great for everybody, because
the
race to sequence the human genome
intensified, and
by the year 2000, five years ahead of
schedule, the human genome was sequenced.
Immediately afterwards, biologists
starting sequencing many other genomes.
And here you see all nine mammalian
genomes
that were sequenced in the next ten years.
It looks like great set of animals and a
large number of biology,
biological sequencing problem.
Obviously, biologist was very busy
sequencing those genomes.
However, they wanted to sequence thousands
of genomes.
And in the framework of existing
technology, it was just not feasible.
The existing technology was very
expensive.
And that's why the number of companies all
over
the world started a race to invent new
next
generation sequencing technologies.
They succeeded.
And they reduced the cost of sequencing by
orders of magnitude.
As a result, we can now move from
sequencing
of a reference human genome, to sequencing
personal human genomes.

Reference human genome represents an

average genome of average
human genome, but we want to find the
differences
between genomes of different humans, and
these differences may appear to be small.
in particular between every two human you
expect
to see roughly one mutation in thousands
nucleotides.
However, these differences may be
extremely important, as
they are responsible for thousands of
genetic diseases.
Personal medicine and personalized
genomics
have important implication in medicine.
And in 2010, Nicolas Volker has become
the poster child of personalized genomics.
His life was saved by genome sequencing.
Poor child went through thousands of
surgeries,
because doctors failed to diagnose his
condition.
Afterwards they decided to sequence his
genome and found a rare mutation in
his gene linked to defect in his immune
system.
As a result, immunotherapy saved the life
of the child.
And obviously human genome sequencing cost
falling
down, we expect that very soon, the cost
of sequencing the human genome will fall
under $1,000 mark.
As a result, sequencing genomes will
probably become as routine as x-ray today.
At the same time, there are numerous
projects to sequence various species.
And in 2010 biologists started 10,000
genome project to sequence 10,000
vertebrate species.
Just think about this, a single human
genome
in 2000, 10,000 genomes in the year 2010.
To accomplish
this genomic revolution.
We need to develop algorithmic techniques
for sequencing genomes and in the
next segment, Dr. Son Pham will tell you
how it can be done.