Bioinformatics and Chips

1
Bioinformatics and Chips

• Bioinformatics is a very integral part of each
  step in a chip project.

2
Steps in a Chip Project
1 Biological question 2 Design experiment 3
Design chip 4 Run experiment 5 Read out chip 6
Treat data 7 Biological answer First overview,
then details
3
Biological Question
A chip experiment is only worth doing, if it
answers a question that is worth asking.
4
Design Experiment
Not every question can be answered with a chip
experiment. Some questions that can be answered
with a chip experiment can also be answered with
another (cheaper) experiment.
5
Design experiment
Probes on the chip Unique Reproducible
6
Run Experiment
Like every binding study, chip experiments have
a thermodynamic and a kinetic component.
7
Run Experiment
Binding thermodynamics DG DH - TDS DG - R T
ln(K) DG 1.4 kCal/M Factor 10 in K 1 H-bond
1 4 kCal/M
8
Chip Read Out is Solved
And, what is more, it has nothing to do with
bioinformatics.
9
Treat Data
I assume this has been discussed in other
sessions in this course.
10
Biological Answer
This is not just bioinformatics. Everything you
know can, and should, be used at this stage.
11
Knowledge needed
No matter what chip-array software you use, you
will want to know all there is to know about the
genes/proteins that are on the chip. So,
up-to-date databases are always needed.
12
Some tools
BLAST SRS KEGG www.cmbi.kun.nl
13
BLAST
14
BLAST
15
BLAST
16
BLAST
17
SRS
18
SRS
19
SRS
20
SRS
21
SRS
22
KEGG
23
KEGG
24
KEGG
25
KEGG
26
KEGG
27
KEGG
28
SwissProt
ID CRAM_CRAAB STANDARD PRT 46
AA. AC P01542 DT 21-JUL-1986 (Rel. 01,
Created) DT 21-JUL-1986 (Rel. 01, Last sequence
update) DT 01-NOV-1997 (Rel. 35, Last
annotation update) DE CRAMBIN. GN THI2. OS
Crambe abyssinica (Abyssinian crambe). OC
Eukaryota Viridiplantae Streptophyta
Embryophyta Tracheophyta OC euphyllophytes
Spermatophyta Magnoliophyta eudicotyledons OC
core eudicots Rosidae eurosids II
Brassicales Brassicaceae OC Crambe.
29
SwissProt
RN 1 RP SEQUENCE. RX MEDLINE
82046542. RA TEETER M.M., MAZER J.A., L'ITALIEN
J.J. RT "Primary structure of the hydrophobic
plant protein crambin." RL Biochemistry
205437-5443(1981). CC -!- FUNCTION THE
FUNCTION OF THIS HYDROPHOBIC PLANT CC SEED
PROTEIN IS NOT KNOWN. CC -!- SIMILARITY
BELONGS TO THE PLANT THIONIN FAMILY. DR
PIR A01805 KECX. DR PDB 1CRN 16-APR-87. DR
PDB 1CBN 31-JAN-94.
30
SwissProt
FT DISULFID 3 40 FT DISULFID 4
32 FT DISULFID 16 26 FT VARIANT
22 22 P -gt S. FT VARIANT 25
25 I -gt L. FT STRAND 2 3 FT
HELIX 7 16 FT TURN
17 19 FT HELIX 23 30 FT
TURN 31 31 FT STRAND 33
34 FT TURN 42 43 SQ SEQUENCE
46 AA 4736 MW F6ADE458 CRC32 gtP1CRAM_CRAAB
TTCCPSIVAR SNFNVCRLPG TPEAICATYT GCIIIPGATC
PGDYAN
31
Significance
32
Pointers
www. cmbi.kun.nl/ www. cmbi.kun.nl/srs/ www.
cmbi.kun.nl/bioinf/tools/blast.shtml www.
genome.ad.jp/kegg/ www. affymetrix.com/ www.
dmd.nl/arrayNL/arrayNL.html www.
gene-chips.com/ (the blank in there is not
real, but needed if you use this Windows thing)
33
Pointers
www. BioASP.nl Bioinformatica.pagina.nl jura.ebi.a
c.uk8765/gqsrv/submit Soon an CMBI/BioASP
Pedant (the blank in there is not real, but
needed if you use this Windows thing)