DNA Microarrays

Patrick Schmid
CSE 497
Spring 2004

What is a DNA Microarray?

Also known as DNA Chip

Allows simultaneous measurement of the
level of transcription for every gene in a
genome (gene expression)
Transcription?

Process of copying of DNA into messenger RNA

(mRNA)
Environment dependant!

Microarray detects mRNA, or rather the more

stable cDNA
Patrick Schmid

What is a DNA Microarray?

(cont.)

Cheung et al. 1999

Patrick Schmid

How do we manufacture a
microarray?

Start with individual genes, e.g. the ~6,200

genes of the yeast genome
Amplify all of them using polymerase chain
reaction (PCR)
Spot them on a medium, e.g. an ordinary
glass microscope slide
Each spot is about 100 m in diameter
Spotting is done by a robot
Complex and potentially expensive task
Patrick Schmid

How do we manufacture a
microarray?

Cheung et al. 1999

Patrick Schmid

Overview of Example

Brown & Botstein, 1999

Patrick Schmid

Reading an array

Laser scans array and produces images

One laser for each color, e.g. one for green, one for
red
Image analysis, main tasks:

Noise suppression
Spot localization and detection, including the extraction of
the background intensity, the spot position, and the spot
boundary and size
Data quantification and quality assessment

Image Analysis is a book on its own:

Kamberova, G. & Shah, S. DNA Array Image Analysis Nuts

& Bolts. DNA Press LLC, 2002
Patrick Schmid

Real DNA Microarray

Campbell & Heyer, 2003

Patrick Schmid

Color Coding

Tables are difficult to read

Data is presented with a color scale
Coding scheme:

Green = repressed (less mRNA) gene in experiment

Red = induced (more mRNA) gene in experiment
Black = no change (1:1 ratio)

Or

Campbell & Heyer, 2003

Green = control condition (e.g. aerobic)

Red = experimental condition (e.g. anaerobic)

We only use ratio

Patrick Schmid

Complication: Time Series

Biologists care more about the process of

adaptation than about the end result
For example, measure every 2 hours for 10 hours
(depletion of oxygen)
31,000 gene expression ratios
Or 6,200 different graphs with five data points each
Question: Are there any genes that responded in
similar ways to the depletion of oxygen?

Patrick Schmid

10

Clustering of example

Campbell & Heyer, 2003

Patrick Schmid

11

Clustering of entire yeast

genome

Campbell & Heyer, 2003

Patrick Schmid

12

Hierarchical Clustering
(cont.)

Eisen et al., 1998

Patrick Schmid

13

References

Brown, P., Botstein, D. Exploring the new world of the genome with
DNA microarrays Nature genetics supplement, vol. 21, January 1999
Campbell A. & Heyer L. discovering Genomics, Proteomics, &
Bioninformatics Benjamin Cummings, 2003.
Cheung, V., Morley, M., Aguilar, F., Massimi, A., Kucherlapati, R. &
Childs, G. Making and reading microarrays Nature genetics
supplement, vol. 21, January 1999
Cho, S. & Won, H. Machine Learning in DNA Microarray Analysis for
Cancer Classification Proceedings of the First Asia-Pacific
bioinformatics conference on Bioinformatics 2003 - Volume 19,
Australian Computer Society Inc.
Eisen, M., Spellman, P., Brown, P. & Botstein, D. Cluster analysis and
display of genome-wide expression patterns Proc. Natl. Acad. Sci.
USA. Vol 95, pp. 14 863-14868, December 1998. Genetics
Seo, J. & Sheiderman, B. Interactively Exploring Hierarchical Clustering
Results IEEE Computer, July 2002
Witten, I. & Frank, E. Data Mining Morgan Kaufmann Publishers, 2000
Patrick Schmid

14