Bi-correlation clustering algorithm for determining a set of co- regulated genes BIOINFORMATICS vol....
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Transcript of Bi-correlation clustering algorithm for determining a set of co- regulated genes BIOINFORMATICS vol....
Bi-correlation clustering algorithm for determining a set of co-
regulated genes
BIOINFORMATICSvol. 25 no.21 2009
Anindya Bhattacharya and Rajat K. De
Outline
Introduction Bi-correlation clustering algorithm
(BCCA) Results Conclusion
Introduction
Biclustering Performs simultaneous grouping on genes and
conditions of a dataset to determine subgroups of genes that exhibit similar behavior over a subset of experimental condition.
A new correlation-based biclustering algorithm called bi-correlation clustering algorithm (BCCA) Produce a diverse set of biclusters of co-regulated
genes All the genes in a bicluster have a similar change
of expression pattern over the subset of samples.
Introduction
Cluster analysis Most cluster analysis try to find group of
genes that remains co-expressed through all experimental conditions.
In reality , genes tends to be co-regulated and thus co-expressed under only a few experimental conditions.
Bi-correlation clustering algorithm
Notation A set of n genes Each gene has m expression values For each gene gi there is an m-
dimensional vector , there is the j-th expression value of gi.
A set of m microarry experiments (measurements)
n genes will have to be grouped into K overlapping biclusters
}g,...,g,{gX n21
}e,...,e,{eY m21
},...,,{ 21 KCCC
ix ijx
Bi-correlation clustering algorithm
Bicluster: A bicluster can be defined as a subset of
genes possesing a similar behavior over a subset of experiments
Represented as A bicluster contains a subset of
genes and a subset of experiments where each gene in is correlated with a correlation valued greater than or equal to specified threshold , with all other genes in over the measurements in .
kC kI
kJ
),( kkk JIC )( XII kk
)( YJJ kk kI
kI
kJ)(
Bi-correlation clustering algorithm
BCCA Use person correlation coefficient for
measuring similarity between expression patterns of two genes and .
ig jg
m
l
m
lijjliil
m
lijjliil
ji
xxxx
xxxx
1 1
22
1
)()(
))((),(Corr xx
Bi-correlation clustering algorithm
Step 1: The set of bicluster S is initialized to
NULL and number of bicluster Bicount is initialized to 0
Step 2A BCCA generate a bicluster (C) for each
pair of genes in a dataset under a set of conditions
For each pair of genes .BCCA creates a bicluster , where and .
)(, jigg ji
),( JIC }{ ji ,ggI YJ
Bi-correlation clustering algorithm
In step 2C: For a pair of genes in C, if then a
sample is detected from C, deletion of which caused maximum increase in correlation value between and .
If being a threshold, the sample is deleted from . otherwise, C is discarded.
Deletion of a measurement for which genes differ in expression value the most will result in the highest increase in correlation value.
BCCA deletes one measurement at a time from .
),(Corr ji xx
3,' rrJm
ig
jg
J
J
Bi-correlation clustering algorithm
In step 2D(a): Other genes from , which satisfy
the definition of a bicluster are included in C for its augmentation.
In step 2D(b): Whether present bicluster C has been
found. If it is so then we do not to include C, otherwise, C is considered as a new bicluster.
IX
Bi-correlation clustering algorithm
Bi-correlation clustering algorithm
Results
Datasets We demonstrate the affectiveness of
BCCA in determining a set of co-regulated genes (i.e. the genes having common transcription factors) and functionally enriched clusters (and atributes) on five dataset
Results
Variation with respect to threshold Plot of YCCD dataset :
Average number of functionally enriched attributes (computed using P-values) versus correlation threshold value
Results
Follow a guideline on this value from a previous study by Allocco et al. (2004) which has concluded that if two genes have a correlation between their expression profiles >0.84 then therre is >50% chance of being bounded by a common transcription factor.
Results
By locating common transcription factors At first, we only consider those biclusters
that have less than or equal to 50 genes. Use a software TOUCAN 2 (Aerts et al., 2005)
for performance comparison by extracting information on the number of transcription factors present in proximal promoters of all the genes in a single bicluster.
Presence of common transcription factors in the promoter regions of a set of genes is a good evidence toward co-regulation.
Results
Results
Sequences of all the five genes found in a bicluster generated by BCCA from SPTD dataset.
Any transcription factor may be found present in more than one location in upstream region.
Results
Functional enrichment : P-value
The functional enrichment of each GO category in each of the bicluster
employed the software Funcassociate (Berriz et al., 2003).
P-value represents the probability of observing the number of genes from a specific GO functional category within each cluster.
A low P-value indicates that the genes belonging to the enriched functional categories are biologically significant in the corresponding clusters.
Results
P-value of a functional category Suppose we have total population of N genes ,
in which M has a particular annotation. If we observe x genes with that annotation, in
a sample of n genes, then we can calculate the probability of that observation.
The probability of seeing x or more genes with an annotation, out of n, given that M in the population of N have that annotation
n
N
xn
MN
x
M
P
n
xj
n
N
jn
MN
j
M
valueP
Results Only functional categories with
are reported. Analysis of the 10 biclusters obtained for the
YCCD, the highly enriched category in bicluster Bicluster1 is the ‘ribosome’ with P-value of
7100.5 P
17102.4
Results
Results
Conclusion
BCCA is able to find a group of genes that show similar pattern of variation in their expression profiles over a subset of measurements.
Better than other biclustering algorithm: Find higher number of common
transcription factors of a set of gene in a bicluster
More functionally enriched