Altklausuren

Question 1

What is Systems Medicine?

In what ways does it dier from and/or extend Systems Biology?

Answer 1

Systems medicine is an interdisciplinary eld that incorporates Systems Biology, Bioinforma-
tics and Medical Informatics to unravel the molecular causes of disease through integration
of patient records, High-throughput data and mathematical modeling. Being embedded in
the eld of Medicine itself, it deviates from basic research by the need to consider Ethical
and Monetary issues as well.

Question 2

What do we understand by the process of preferential attachment in network biology?
To which type of network does this process lead to?
How does the resulting network topology help to better understand cancer?

Answer 2

Preferential attachment is a process wherein new nodes in a growing network are likely to
attach to nodes of high degree. This creates a modularized, scale-free network with few hub
nodes.
Hub nodes are essential for the network integritiy. The eect of hub perturbations radiate
out through the entire network. Tumor suppressor genes and oncogenes, i.e. genes that are
frequently mutated in cancer and are causative for the disease, are therefore often hub nodes
in the interactome network of a cell.

Question 3

Given a reaction following the Michaelis-Menten Kinetics mark in the plot below the ran-
ges for rst-order/intermediate/zero-order kinetics and explain the kinetics order from the
formula for the reaction rate .
What is the reaction rate and substrate concentration the intersection of the dashed lines?

For estimation of the Michaelis Menten parameters, derive a linear relationship between the
reaction rate , KM and the maximal reaction speed Vmax and explain how to estimate the
parameters from this linear equation.

Answer 3

For estimation of the MM parameters, you can use the Lineaver-Burk, Eadie-Hofstee or
Hanes-Woolf inversion that give you the reaction speed in terms of the inverse of the the
Substrate concentration and maximal turnover speed.

Question 4

Which are the main factors shaping the composition of the gut microbiota?
Give a denition of alpha and beta diversity!
What is the main dierence between them?

Answer 4

Among others, the following in
uence the gut microbiome: Age, diet (e.g. Western diet,
Vegetarian, Vegan, Non-western, ), stress, in
ammation (cause and/or consequence), envi-
ronment, medication (e.g. antibiotics), …
Alpha diversity refers to the richness/diversity of a community (local species pool) whereas
beta diversity denes the total species diversity (dissimilarity between communities).
Alpha diversity is measured within a community, beta diversity among communities.

Question 5

What are positive and negative autoregulation and how are they used by the cell in dynamic
regulation?

Answer 5

Positiv autoregulation (PAR) occurs, when the product of a gene activates its own produc-
tion. PAR is a common network motif in transcritpton networks but occurs less often in the
E. coli network than negative autoregulation. Positive autoregulation can lead to bistability.
2
Negative autoregulation (NAR) occurs when the product of a gene represses its own pro-
duction. NAR is a common network motif in transcritpton networks. Circuits with negative
autoregulation speed up the response time and show increased robustness against parameter fluctuations.

Question 6

Plot the potential for the system
x° = x - x^3
and identify all equilibrium points.
Can you give an example of a biological systems whose dynamics might have such a potential?

Answer 6

V (x) = -1/2x^2 + 1/4 x^4
Equilibrium points at x = [0;-1; 1]
Biological examples are e.g. cell fate decisions, cell differentiation or any decision that leads
to bistability.

Question 7

Name and describe the main features of Genetic Algorithms (GA)?
What problems are GA used for and give an example of such a problem!

Answer 7

A GA consists of a population that reproduces according to their tness to create ospring
with a mutated /recombined genome. The child generation is evaluated against the solution
using some tness function and the process of reproduction is started over until some cuto
criterium is met.
Usually a GA is used to solve complex optimization problems, i.e. the traveling salesman
problem

Question 8

What are kinases and what are proteases?

Why are they important for signal transduction in the cell?

Answer 8

Kinases and proteases are enzymes. A kinase adds a phosphor residue to another protein
thereby changing its structure and thus its function. Proteases are enzymes that control the
cleavage of other proteins and thereby inhibit the function of the cleaved protein.

Question 9

What is cooperative binding in chemical reactions?

Answer 9

It describes the eect, that the anity of a protein to bind changes with the amount of
protein already bound.

Question 10

Which type of equation describes cooperativity?

Answer 10

The Hill Equation

Question 11

Name and describe a biological example, where cooperativity of chemical reactions plays an
important role.

Answer 11

Binding of oxygen to hemoglobin.

Question 12

Dene the term microbiome!
We talked about the role of bacteria in our life in the lecture. Brie
y discuss whether bacteria
are usually harmful or benecial for us.
Does the microbiome composition changes through life time (e.g. in the gut)? Explain if and
how it changes from unborn to elderly (unborn-baby-toddler-adult-elderly)!

Answer 12

The Microbiome: - Ecological community of commensal, symbiotic and pathogenic microor-
ganisms that share our body space
- Comprises bacteria, viruses, fungi, and tiny other organisms
Harmful or benecial?
Mainly benecial, because e.g. they help to digest food and provide nutrients, are part of
the immune response, …
Composition through life?
Unborn - mainly sterile, baby - small diversity, toddler - diversity growths with respect to life
style, adult - most diverse community (heavily dependent on life style and diseases), elderly
- reduced diversity

Question 13

What is an Ontology? Provide an example of an ontology and describe how an ontology can
be used in the biological interpretation of experimental data.

Answer 13

A set of concepts and categories in a subject area or domain that shows their properties and
the relations between them. (Denitions may vary, but you were all correct about this.)
The Gene Ontology is an example of an ontology that relates Biological processes and esta-
blishes an ordered hierarchy of terms. Genes and proteins are annotated with GO terms.
Enrichment tests can be used to identify GO terms that are signicantly overrepresented in
a subset of genes and thus relate this set to biological function.

Question 14

Determine the stability of the equilibrium point(s) of the following one dimensional systems.

1. x° = -x^3
2. x° = x^2-1
3. x° = x^2 + 1
4. x° = x - x^3
5. x° = 1 - 2 cos(x)

Answer 14

1. x* = 0 stable
2. x* = 1 unstable, x* = -1 stable,
3. no equilibrium points
4. x* = -1 stable, x* = 0 unstable, x* = 1 stable
5. x* = arccos(1/2 + 2kpi) unstable, x* = - arccos(1/2 + 2kpi) stable, for integer k

Question 15

Which network most closely resembles the protein-protein interactome of a mammalian cell?

Answer 15

Scale Free network

Question 16

Can you name and briefly explain a method how to nd the interactome in mammalian cells
on a large scale basis?

Answer 16

For example a yeast 2 hybrid screen.

Question 17

Explain the existence and function of Oncogenes and Tumor suppressor genes in terms of
network topology of the cellular interactome!

Answer 17

Oncogenes and tumor supressor genes are highly connrected network hubs in the cellular
interactome. Their disfunction has widespread consequences on the network topology and
thus theirs eect reaches many cellular processes.

Question 18

An MLS students wants to nd out whether two proteins in a mammalian cell are interac-
ting - possibly indirectly - with each other. Therefore, the student downloads the protein
interactome and calculates the shortest path between the two proteins on the network. If
the shortest path is short, the proteins are likely to interact, if the path is long then it is
unlikely that the proteins interact. Is this a good or bad approach to predict putative protein
interactions? Explain why!

Answer 18

Biological network have small world properties. The shortest path between proteins is usually
short and does not dier much between directly interacting and non-interaction proteins.
Therefore it is hard to dene path distance cutos that distinguish between interacting and
non-interaction proteins.

Question 19

What is Systems Biology? In what ways does it dier from ‘classical’ biology?

Answer 19

Systems Biology investigates inter- and inner-cellular dynamic processes using systems theoretic approaches.
It combined Systems Theory with molecular biology with the goal to obtain a causative understanding of the
molecular principle of life. In doing so it relies on quantitative data from many sources from genomics. proteomics,
or clinical data.
This is in contrast to classical biology, which is most often a descriptive, i.e. qualitative, science.

Question 20

What is meant with the time scale of a process?
Order the following processes with a mammalian organism in terms of their time scale from short to long:
Acquisition of somatic mutations; protein signaling; organ growth; gene expression; protein complex formation

Answer 20

The time scale c of a process denotes the characteristic, i.e. the average time for its completion. For example
the half-life of a protein denotes a characteristic time scale for its decay.
Order of time scales from short to long:
protein complex formation; protein signaling; gene expression; organ growth; somatic mutations

Question 21

What is cooperative binding in chemical reactions?

Which mathematical equation describes cooperativity?

Answer 21

Cooperativity denotes the process, in which proteins have multiple binding sites that act dependently on each
other thereby increasing or decreasing the binding anity of substrates or ligands depending on the number of
occupied binding sites.
The Hill equation is a mathematical formalism that simulates the cooperativity through the exponent n.

Question 22

What are the elements of a graph?
Why is a graph a useful tool for biology? How does the degree distribution of a biological network dier from a
random network and what are the biological consequences?

Answer 22

A graph is an ordered pair G=(V,E), comprising a set of V nodes together with a set E of edges.
Proteome in the cell forms a network that can be described using graph theory.
Biological networks show scale-free behavior w.r.t. degree distribution. Existence of hubs, which are crucial in
cell regulation, but robust against failure of many low connected nodes.

Question 23

What is Systems Biology?

In what ways does it dier from ‘classical’ biology? (Brief answer!)

Answer 23

Systems Biology investigates the dynamic interactions if proteins and genes using systems
theoretic methods. It stresses that only through the study of the dynamic interactions alone,
one can nd the emergent processes that make up life.

Question 24

What do we understand by the process of preferential attachment in network biology?
To which type of network does this process lead to?
How does the resulting network topology help to better understand cancer?

Answer 24

Preferential attachment is a process wherein new nodes in a growing network are likely to
attach to nodes of high degree. This creates a modularized, scale-free network with few hub
nodes.
Hub nodes are essential for the network integritiy. The eect of hub perturbations radiate
out through the entire network. Tumor suppressor genes and oncogenes, i.e. genes that are
frequently mutated in cancer and are causative for the disease, are therefore often hub nodes
in the interactome network of a cell.

Question 25

Given a reaction following the Michaelis-Menten Kinetics mark in the plot below the ran-
ges for rst-order/intermediate/zero-order kinetics and explain the kinetics order from the
formula for the reaction rate .
What is the reaction rate and substrate concentration the intersection of the dashed lines?
For estimation of the Michaelis Menten parameters, derive a linear relationship between the
reaction rate , KM and the maximal reaction speed Vmax and explain how to estimate the
parameters from this linear equation

Answer 25

Figure!!
For estimation of the MM parameters, you can use the Lineaver-Burk, Eadie-Hofstee or
Hanes-Woolf inversion that give you the reaction speed in terms of the inverse of the the
Substrate concentration and maximal turnover speed. (see Lecture notes from Oct. 26th).

Question 26

Which are the main factors shaping the composition of the gut microbiota?
Give a denition of alpha and beta diversity!
What is the main dierence between them?

Answer 26

Among others, the following in
uence the gut microbiome: Age, diet (e.g. Western diet,
Vegetarian, Vegan, Non-western, ), stress, in
ammation (cause and/or consequence), envi-
ronment, medication (e.g. antibiotics), …
Alpha diversity refers to the richness/diversity of a community (local species pool) whereas
beta diversity denes the total species diversity (dissimilarity between communities).
Alpha diversity is measured within a community, beta diversity among communities.

Question 27

What are positive and negative autoregulation and how are they used by the cell in dynamic
regulation?

Answer 27

Positiv autoregulation (PAR) occurs, when the product of a gene activates its own produc-
tion. PAR is a common network motif in transcritpton networks but occurs less often in the
E. coli network than negative autoregulation. Positive autoregulation can lead to bistability.
Negative autoregulation (NAR) occurs when the product of a gene represses its own pro-
duction. NAR is a common network motif in transcritpton networks. Circuits with negative
autoregulation speed up the response time and show increased robustness against parameter

uctuations.

Question 28

Plot the potential for the system
x° = x - x^3
and identify all equilibrium points.
Can you give an example of a biological systems whose dynamics might have such a potential?

Answer 28

V (x) =-1/2x^2 + 1/4 x^4
Equilibrium points at x = [0;-1; 1]
Biological examples are e.g. cell fate decisions, cell differentiation or any decision that leads
to bistability.

Question 29

Name and describe the main features of Genetic Algorithms (GA)?
What problems are GA used for and give an example of such a problem!

Answer 29

A GA consists of a population that reproduces according to their tness to create ospring
with a mutated /recombined genome. The child generation is evaluated against the solution
using some tness function and the process of reproduction is started over until some cuto
criterium is met.
Usually a GA is used to solve complex optimization problems, i.e. the traveling salesman
problem