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Darwin
What happened next?
• Followed by influx of research on genetic
materials in cells
• Discovery of DNA, composition of genes,
relationship between genes and proteins, gene
cloning
• Ian Wilmut and his colleagues cloned Dolly from
adult cell (1997)
• Completion of the human Genome Project (April
2003)
• The “Omics” era
Key areas in Molecular Biology
• Biological insight
• Careful planning
Why do we need to design experiments?
• To minimize:
• random variation
– inter-sample variation,
– within-treatment variation (noise)
• To account for:
• confounding factors
– Confounding variables
– Variables that affect the relationship (the data you
are collecting) between independent variable and
dependent variable (False correlation)
– As a result, you may ended up analysing the
results/ data incorrectly.
– Eg. third variables
Stages in Experimental Design
1. Preliminaries
2. Structure
3. Measurements
4. Final checks
1. Preliminary : Define hypothesis
Experiments should be focused:
Question
Hypothesis
Prediction
2. Structure:
How to test the hypothesis?
• Correlational study
• Use of naturally occurring variation
• No (as little as possible) investigator interaction
• Manipulative study
• Studying the effects of artificial manipulation
• The investigator does something to the subject of
study in order to find out the effects this
manipulation has on a particular process or system
a. Correlational study
• Advantages:
• Easier
• Saves time and effort
• Does not cause any unintended harm to the
subject
• Biologically relevant variation
• Disadvantages:
• It is affected by third variables
• It is affected by reverse causation
b. Manipulative study
• Advantages:
• Not affected by third variables
• Not affected by reverse causation
• Disadvantages:
• Difficult
• Longer & involves more work
• May cause unintentional harm to the subject of study
• The manipulation may not be biologically relevant
Third variables and reverse causation?
Example:
Study on the relationship
between Fetal Development and
Gum Disease
E.g. of third variables and reverse causation
Situation 1
Gum disease (Variable A) in pregnant
mothers causes abnormal fetal
development (Variable B) .
The abnormal fetal development leads to
lower birth weights. Perhaps the mother’s
immune system is using too much energy to
fight off the disease — energy that then is
not available to the developing fetus.
E.g. of third variables and reverse causation
Situation 2
Abnormal fetal development (Variable B)
causes gum disease in pregnant mothers
(Variable A) Perhaps the abnormal
development is sapping the mother’s
strength, thereby leaving her more
vulnerable to various diseases.
Situation 3
A third variable (Variable C) causes the
development of maternal gum disease
(Variable A) and abnormal fetal
development (Variable B) .
Perhaps impoverished pregnant women
(poverty being an unmeasured third
variable) are less likely to have adequate
health care, which leaves both the women
and their developing fetuses more
vulnerable to disease.
Deciding on the appropriate
approach
The decision depends on the research
questions
• Field vs. Laboratory
• in vivo vs. in vitro
How to control random variation
or noise?
• Replication
• Measurements on a number of independent
experimental subjects that have been subjected to
the same manipulations
• Randomization
• Random samples from a large population of
individuals
• Beware of haphazard sampling
Watch out for pseudoreplication!
• If the samples (or experimental subjects) are not
independent,
• Experiment is being pseudoreplicated; not replicated
• Examples:
• Multiple measurements on the same individual as if they
were independent measurements
• Measurements taken from genetically related individuals
are not independent
Controls
• A control is:
• A reference against which the results of an experiment can
be compared
• Negative control
• The control group is not subjected to any manipulation or
treatment
• Positive control
• The control group is manipulated in the same way as the
treatment group
• Do not overwork
• Sequential sampling
• Stratified sampling
• Systematic sampling
Sampling schemes
1. Random sampling (most commonly used)
• Subject chosen by a method involving an unpredictable
component.
• Sampling error: random variation in the results.
Conclusion
Sampling schemes
3. Stratified sampling
• Is a method of sampling from a population.
• Stratification: the process of dividing members of the
population into homogeneous subgroups before sampling.
Every element in the population must be assigned to only
one stratum. The strata should also be collectively
exhaustive: no population element can be excluded.
• Proportionate allocation uses a sampling fraction in each of
the strata that is proportional to that of the total population.
For instance, if the population consists of 60% in the male
stratum and 40% in the female stratum, then the relative size
of the two samples (three males, two females) should reflect
this proportion.
• Drawback: It is not useful when there are no similar
subgroups.
http://www.formyschoolstuff.com/school/math/glossary/s.htm
Sampling schemes
4. Systematic sampling
• Is a random sampling technique which is frequently chosen by
researchers for its simplicity and its periodic quality.
• In systematic random sampling, the researcher first randomly
picks the first item or subject from the population. Then, the
researcher will select each “n”'th subject from the list.
• For example, the researcher has a population total of 100
individuals and need 12 subjects. He first picks his starting
number, 5. Then the researcher picks his interval, 8. The members
of his sample will be individuals 5, 13, 21, 29, 37, 45, 53, 61, 69,
77, 85, 97.
• Starts from No.2
• Take sample from every third person
Supporting materials:
https://www.youtube.com/watch?v=SMGRe824kak
Preliminaries
Structure
Measurements
Final Checks
Self study:
1. Experimental Design in Science: Definition and Method
(Youtube: https://www.youtube.com/watch?v=7q8acfBx5to)
2. Understanding Research Design:
(Youtube: https://www.youtube.com/watch?v=kJ01TMt0XJk)
3. The Scientific Method:
(Youtube: https://www.youtube.com/watch?v=tUP8rFWzVt4)
References:
1. Graeme D. Ruxton and Nick Colegrave (2003) Experimental Design for
the Life Sciences. Oxford University Press, Oxford, UK.
2. Alan G. Clewer and David H. Scarisbrick. (2001) Practical Statistics and
Experimental Design for Plant and Crop Science. John Wiley & Sons Ltd.
3. Gerry P. Quinn, Michael J. Keough (2002) Experimental Design and Data
Analysis for Biologists. Cambridge University Press, Cambridge, UK.
4. bio.hubu.edu.cn/doc/fenzi2.ppt
Take away key points
• How to design your own experiment?
• Experimental design
1. Preliminaries: Question, Hypothesis,
Prediction
2. Structure: Correlational study,
Manipulative study
3. Taking measurements: Random sampling,
Sequential sampling, Stratified sampling,
Systematic sampling
4. Final checks