Computational physiology and in silico medicine

Question 1

computational framework

Answer 1

for understanding human physiology → encoding models & data
- including establishment of standards for encoding models & data

Question 2

computational modelling

Answer 2

of biological processes to integrate quantitative biological knowledge from molecular to cell, tissue, organ and whole body scales

• understand physiological systems in terms of molecular components and their interaction with the environment
• translate understanding into clinical practice

Question 3

the physiome project

- principles and challenges

Answer 3

• developing a multiscale modelling framework
• models combined & linked in hierarchical fashion
  challenges
• use standards
• generally accepted framework for model sharing

Question 4

the virtual physiological human initiative

- principles and challenges

Answer 4

• computer technologies to integrate all information available
• computer models capable of predicting health evolution under certain conditions
  challenges
• higher degree of automation of pre-& post processing of patient-specific models
• faster turnaround

Question 5

in silico modelling- multiple biological scales

Answer 5

• physiological systems → feed-forwad pathways btw successive levels and feedback pathways that span levels of biological organisation
• physiological function: distributed across multiple biological scales & does not necessarily originate form any one level

Question 6

consequences of in silico modelling

Answer 6

• leads to high complexity of physiological systems
• understanding extremely challengig
• can potentially be achieved through quantitative modelling

Question 7

in silico models overview

Answer 7

according to each scale of physiological system there is an in-silico model

• molecules: algebraic model
• networks: topological, statistical, dynamical, agent-based models
• cells: dynamic & agent-based models
• tissue: dynamical & agent-based
• organs: dynamical, agent-based & geometrical models
• organ system: dynamical & geometrical models

Question 8

algebraic models

Answer 8

describe classes of objects in the genome and their relationship
- Example: Boolean networks of molecular interaction

Question 9

topological models

Answer 9

describe molecular wiring diagrams

- e.g. membrane protein folding

Question 10

statistical models

Answer 10

describe molecular networks as joint probability distribution of molecular concentrations

Question 11

dynamical models

Answer 11

describe the spatiotemporal evolution of biological states using ordinary or partial differential equations
e.g. ordinary differential equation model of tumor growth

Question 12

agent-based models

Answer 12

describe physiological system component interactions using rules

e. g. cellular automaton predicting microvascular patterning
- cellular automaton integrating genetic, molecular and cellular signals

Question 13

geometric models

Answer 13

describe anatomic shape

e.g. osteoarthritis diagnostics based on bone shape

Question 14

in silico clinical trials

Definition

Answer 14

Definition: use of individualized computer simulation in development or regulatory evaluation of a medicinal product, medical device or medical intervention
→ make use of computer modelling and simulation in medicine

Question 15

Motivation for in silico clinical trials

Answer 15

• always testing on human/animals to ensure the safety and efficancy of biomedical product
• complexity of diseases, differences btw patients, treatment administration variability → often lead to problems in clinical trials
• clinical trial often do not tell us why a product fails or suggest how to improve it

Question 16

the 3R principle

Answer 16

Reduce
- only as much animal experiments as necessary
- in vivo imaging
- in silico modelling
Refine
- minimize stress and burden of the animal
- replace invasive measurements
- improving usefulness of in vivo trials
Replace
- replace animal experiment by another method

Question 17

in silico meaning

Answer 17

• allusion to in vivo, in vitro and in situ and means “performend on a computer” or “performed via computer simulation”