Including the effects of Post-transcriptional processing in order to improve the analysis of surveys of GeneChips

Manolo Arteaga-Salas, Jo Rowsell, Harry Harrison Tim Earl, Renata Camargo, Caroline Johnston, W. B. Langdon.
William B. Langdon, Renata da Silva Camargo, Joanna Rowsell, Jose Manuel Arteaga, Graham Upton and Andrew P. Harrison Department of Biological Sciences & Department of Mathematical Sciences at University of Essex

Some genes are represented by multiple probe-sets.

Probe-set A Probe-set B

If they are measuring the same gene the signals should be up and down regulated together! Is that always true? No! Stalteri and Harrison, 2007, BMC Bioinformatics, 8:13.

M A plot

rat chromosome 1
strand 5' 3'
exon 1 exo 2 exon 3 exon 4 exon 5 exon 6
length of 25-mer probe
Probes map to different exons.

Because of alternative splicing, some of the exons may be upregulated whereas others may be downregulated.

chromosome 2 Surf4
poly A signal 
1416213_x_at probes
1436797_x_at probes
1448255_x_at probes
1434589_x_at probes
1455822_x_at probes

Probes map to different sides of a polyadenylation signal. Because of alternative polyadenylation, some of the probes may be upregulated whereas others may be downregulated.

Some probes can be used to study the expression of intergenic exons in chimeric transcripts.

MASK BP3 Chimeric transcript Probes 67520_at

Binds to the gene of interest and to 50 other places in the transcriptome.
Exon 1
Exon 2
Eon 3 & 4 Junction
Doesn't map to a gene of interest
Upstream of a polyA signal
Downstream of a Poly A signal
Binds beyond the 3' end of the gene and is associated with cancer.

A heat-map of the correlation between probes for the same gene across 6685 GeneChips

6685 GEO HG-U133A 208772_at PM 1:11

Presented at CAMDA 2007, 13-14 December 2007. W. B. Langdon 8 Jan 2008.