Hello.

Welcome to Dynamical Modeling Methods for

Systems Biology.
My name is Eric Sobie.
I'm an associate professor at Icahn School
of
Medicine at Mount Sinai in the
Pharmacology Department,
and I'm going to be the instructor for
your course, Dynamical Modeling Methods
for Systems Biology.
Thank you for, for signing up and I look
forward to working with you as, we, we
teach
about different methods that are used in
systems biology
to analy, to analyze and implement
dynamical mathematical models.
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In this first video, topics that we're
going to cover are illustrated on this
outline.
We're going to talk, we're going to
discuss the overall course goals.
We're going to discuss the specific
biological topics and
mathematical topics that are going to be
covered in the course.
And then we're going to review the overall
structure of the course
and how we're going to perform grading and
assessment in this course.
The overall goals of this course,
Dinamical
Modeling Methods for Assistance Biology,
are three fold.
First we want to teach contemporary
methods that
are used in systems biology for dynamical
modeling.
Second we want to teach methods for
mathematical analysis of biological
systems and simulation output.
In other words you implement a model, then
you
get some output from the model, so what
sorts of
approaches do you use to analyze that
output, and
gain more insight into the biological
system, through that analysis?
And then, third, we want to demonstrate
how
dynamical mathematical models can provide
novel insight,
the type that you cannot begin to get if
you, you're only doing experiments.
So the combination of experiments with
dynamical
mathematical models is going to provide

novel insight
that is very difficult to get, or
sometimes
impossible to get, just from the
experiments themselves.
So, what do we mean when we talk about
dynamical mathematical models?
Well, I think it's helpful to divide
different computational
approaches, different types of
mathematical models into two categories.
And I like to differentiate between
statistical, or what I call
top-down models, versus dynamical, or what
I also call bottom-up models.
So what do I mean by that?
Well, the approach you take in a top down
model, can be summarized as follows.
You begin with the dataset and often a
very large dataset very large scale
dataset, the kind that you might get
in a genomics experiment or audiomics
experiment.
Then you use statistical methods to find
patterns in that, in that data set.
And then once you've used statistical
methods to
find patterns in that data set you can
generate predictions, and the predictions
are based on
the structure that you've uncovered within
the data.
And so some of the keywords that you
can associate with this, top down approach
are things
like network analysis gene set enrichment
analysis, clustering
algorithms, principal component analysis,
or, or partially squares regression.
Now I should note that these top down
approaches to doing mathematical
modeling, these statistical models are not
the focus of this course here.
These top down approaches were taught in a
Coursera
course that was offered by my coleague
from Mount Sinai,
Dr. Avi Ma'ayan and Dr. Ma'ayan is
planning to offer
this course through Coursera again in the
next few months.
So if your primary interest is in these
types of models, learning clustering or
learning principal components I would
encourage you
to take a look at Dr. Ma'ayan's course.
Our focus here is going to be on a
different category of model.
What I, what I like to call dynamical
models, or what I also call bottom models.

So the approach here is sort of the

opposite
of what we saw with the top down model.
With the bottom up model, you begin with a
hypothesis of biological mechanism.
Once you have this hypothesis you write
down some equations, to
describe how the components in your
biological system interact with one
another.
Then you run simulations to generate the,
to
generate predictions for what would happen
under different conditions.
And some of the keywords that are
associated with bottom up models, are
things like ordinary differential
equations, tools
of dynamical systems to interpret the
output.
Methods for parameter estimation, partial
differential equations and stochastic
models.
Now in this course, we're not going to be
able to cover
everything, so we're going to focus on the
first two keywords in here.
Models consisting of systems of ordinary
differential equations and tools of
dynamical systems in order to interpret
the, the results of these simulations.
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And this dichotomy of statistical models
versus dynamical models has
been discussed in the literature in, in,
in several review articles.
Including one of ours.
This is an article that my colleagues and
I published.
It describes a course, that we developed
at Mount Sinai School of Medicine.
And this, this Coursera course is devolved
in many ways
from this course that, that we teach at,
at Mount Sinai.
So if you're interested in, in learning
more about
this, this, dichotomy of, of statistical
versus dynamical models.
I would encourage you to, to check out
this article.
And there's other articles in the, in the
same category and it, you
know, in the same class that also
discuss distinctions between different
categories of models.
I think it's worthwhile to review the
general structure
that you frequently see with a dynamical
modeling study.

They actually give you some sense of what

are the steps are, that are involved.
And what kind of insight do we get from
this type of study.
So usually in a dynamical, mathematical
modeling study
you begin with some idea of the mechanism.
What happens biologically.
So I've just illustrated this, with a
simple example here.
Where you have some biological species B
can get converted into some other species
C.
And this protein, the species A might
regulate conversion of B to C.
For instance, A could be an enzyme that
catalyzes conversion of, of B into C.
Once you know something about the
mechanism
or you hypothesize something about the
mechanism.
You write down some equations describing
how the
different components in the system
interact with one another.
And this is an example where we have two
equations and these are in the category of
ordinary
differential equations; that describe how
a particular system, how
the components of a particular system
evolve with time.
Once you've written down the equations
then
you write a program to simulate those
equations.
These are the first two lines of a, of a
program the does such a simulation.
The programming environment we're going to
use to, to write these programs
to simulate our ordinary differential
equations base models is called mat lab.
And so we're going to have several
lectures to introduce you to the MATLAB.
Programming environment before we show you
examples
of dynamical,mathematical models that are
implemented using MadLab.
Once you have your program, you run
simulations
with your with your program that simulates
the equations.
So this is solving the temporal evolution
of one species and another species.
And you can see that the black one is
oscillating with respect
to time, and the red one is oscillating
with respect to time.
Although the actual shape of the
oscillation is different between the

one that's represented in black and the

one that's represented in red.
So then, after you've run these
simulations,
how do you make sense of them?
Well then you often use tools of the
field of dynamical systems to analyze your
output.
And one of the things that you might
do frequently, is you might vary some
parameter
and then you might look to see how your
output changes as you vary this parameter.
And this is a case where you, un, under
low values of the parameter.
You can get, high values of output,
alternating with low values of output.
That would be analagous to these
oscillations we're seeing over here.
But then with higher values of the
parameter
you only get a middle value of the output.
So in his case the oscillations have, have
ceased.
So, by running these types of simulations
where
you vary a parameter and you analyze the
output you can gain insight into how the
behavior of the system changes under
different conditions.
So this is the general structure of a
dynamical modeling study, from mechanism
to equations, to
a program that simulates the equations, to
simulation
results, and then to analysis of the
output.
Now, let's discuss some of the logistics
of this course.
The format that we're going to, that we're
going to take is as follows.
It's going to be a seven week total
course, consisting
of approximately 25 lectures; each lecture
being approximately 20 minutes.
If we take 25 lectures divide that into
seven weeks, we see that
we're going to post somewhere between
three
and four lectures per week on average.
At the end of each lecture we're going to
provide you with one or more self
assessment questions.
This is a way for you to think about what
you've what you've learned in the lecture,
try to answer the question to assess for
yourself;
how well you've understood the material in
the lecture
And then the over all assessment is going

to be based on five homework assignments.

They're going to be given after each
lecture block so
the 25 lectures are going to be divided
into five blocks.
Each of these five blocks is going to be
associated with a homework assignment.
And then passing the course is going
to depend on completing these five
homework assignments.
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The skills that we wish to teach you in
this course are, are the following.
First we want to teach you the use this
programming environment
called MATLAB to be able to perform data
analysis and data visualization.
Next we want to teach you how to develop
models consisting of systems of ordinary
differential equations.
And throughout this course we're going to,
abbreviate
ordinary differential equations, with
ODEs, like that.
Then we want to teach you how to implement
ODE models
in MATLAB and how to run simulations with
these models.
And then finally we want to teach you how
to
analyze ODE models using the tools of
dynamical systems analyses.
And one of the arguments that we're
going to make, as we go through
this course, is that models can be
used for understanding several different
biological processes.
And some of the biological processes that
we're
going to discuss in this course are the
following.
We're going to talk about glucose
oscillations in yeast.
We're going to talk about kinase signaling
pathways in mammalian cells.
We're going to talk about regulation of
the cell cycle.
This is a case where mathematical models
have
been extremely successful and extremely
important in understanding.
Weather or not cells want to divide or
weather they want to stop dividing.
And we're also going to talk about
mathematical models of electrical
signaling in neurons.
That's another classic case where
mathematical models have been really
critical for getting a quantitative
understanding of how the biology works.

And the overall goal is provide you with

the
tools necessary to apply these types of
models to
your own questions of interest, so some of
you
might be interested in some of these
specific biological questions.
But many of you are you know, might have
some
interest in some other biological
mechanism, or some other biological
pathway.
But the hope is that if we teach you the
tools, you can use the same tools
to whatever system it is that you're the
most interested, that you have the most
interest in.
How are we going to perform assessment,
self-assessment in this class?
Self-assessment is going to be performed
by providing you with
one to two questions at the end of each
lecture.
And we're going to, I'm going to introduce
the question.
Give you some time to think about it.
And then after you think about it and
answer
it for yourself, I'm going to go through
the explanation.
So this will be a way for you to, think
about what you've
heard in each lecture and try to apply the
concepts that you've heard.
And then you can see for yourself how
well you understood the material that was
covered.
Overall assessment in this course is going
to be performed through the homework
assignments.
The homework assignments are going to
require
you to perform simulations with dynamical
models.
Because this is a course on teaching you
methods, on teaching
teaching you the sorts of approaches that
are used in systems biology.
The way that you're going to really learn
these approaches is by doing the
simulations yourself.
So the homework assignments are going to
ask you to perform simulations with
dynamical models.
And the general format we're going to use
is not
to make you write the the entire model
from scratch.
We're going to provide you with some

MATLAB code that does one

thing, that might run a simulation of, of
a particular biological system.
And then we're going to ask you to adapt
it,
to modify it in order to do something
else.
And then we're going to provide you with
assessment questions that
are designed to, to verify first of all
that you've implemented
the model correctly, and also that you can
get some biological
interpretation from the results that
you've obtained with that mathematical
model.
So we want to test both your your
programming skills to implement
it correctly and that you can
get biological interpretation from your
results.
And this is to sort of reiterate what I
just said on the last slide.
Homework assignments are designed to
reinforce
concepts that are discussed in the
lectures.
And the assignments should require you to
demonstrate three things.
One is technical competence.
Can you actually implement the model
correctly?
Second, quantitative skills.
Can you get a can you get
a reasonable quantitative interpretation
of your simulation results?
And third, can you use this mo, the model,
can you use the, the simulation results?
To obtain new biological insight, into the
particular
problem and into the particular system
that you're looking
at.
So thank you for listening.
That concludes our first lecture, and I
look forward to working
with you in this course, Dynamical
Modeling Methods for Systems Biology.
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