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Clustering is the process of organizing
objects into groups whose members are similar in
some way, and different from members of other
groups. Clustering is an efficient data mining
technique that finds its usage in various fields.
Clustering and Classification can be merged for
better result solutions and also they complement each
other. They can be used together as the traditional
pattern recognition methods. With the advancement
in the field of microarray technology, cluster analysis
of the genes is made possible has many applications,
by providing insight to the structural, functional and
organisational aspects of gene data sets. Traditional,
Hierarchical, Density-based and Evolutionary
clustering algorithm for gene expression are
discussed. Evolutionary Approaches include
Clustering based on Genetic Algorithm. Special
characteristics of gene expression data and the
particular requirements from the biological domain,
gene-based clustering presents several new
challenges are also listed finally.

Clustering is the process of organizing
objects into groups whose members are similar in
some way, and different from members of other
groups. Clustering is an efficient data mining
technique that finds its usage in various fields.
Clustering and Classification can be merged for
better result solutions and also they complement each
other. They can be used together as the traditional
pattern recognition methods. With the advancement
in the field of microarray technology, cluster analysis
of the genes is made possible has many applications,
by providing insight to the structural, functional and
organisational aspects of gene data sets. Traditional,
Hierarchical, Density-based and Evolutionary
clustering algorithm for gene expression are
discussed. Evolutionary Approaches include
Clustering based on Genetic Algorithm. Special
characteristics of gene expression data and the
particular requirements from the biological domain,
gene-based clustering presents several new
challenges are also listed finally.

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A Survey on Clustering Approaches for Gene Expression Patterns

Irene Maria

1

, Mathew Kurian

2

1

Department of Computer Science and Engineering, Karunya University, India

2

Department of Computer Science and Engineering, Karunya University, India

ABSTRACT Clustering is the process of organizing

objects into groups whose members are similar in

some way, and different from members of other

groups. Clustering is an efficient data mining

technique that finds its usage in various fields.

Clustering and Classification can be merged for

better result solutions and also they complement each

other. They can be used together as the traditional

pattern recognition methods. With the advancement

in the field of microarray technology, cluster analysis

of the genes is made possible has many applications,

by providing insight to the structural, functional and

organisational aspects of gene data sets. Traditional,

Hierarchical, Density-based and Evolutionary

clustering algorithm for gene expression are

discussed. Evolutionary Approaches include

Clustering based on Genetic Algorithm. Special

characteristics of gene expression data and the

particular requirements from the biological domain,

gene-based clustering presents several new

challenges are also listed finally.

Index Terms: Clustering, Fuzzy Partitioning, Gene

Expression, Genetic Algorithm, Microarray.

1. Introduction

Clustering needs a unique and clear decision

about the clusters to be formed. A few clustering

algorithms which focuses on categorical data have

been developed. But in most cases, the measures

contributing to the clusters may not be appropriate.

There is an increasing interest in clustering methods

when used in pattern recognition, image processing

and information retrieval and also in fields like

biology, geology and marketing.

1.1 Clusters and Clustering

Clustering is an important real world problem.

Clustering is a suitable example of unsupervised

classification. It is the process of grouping data

objects into a set of classes. These classes called

clusters may have entities with high similarity and

dissimilarity with entities in other clusters. So

clustering can be used to find rules for classifying

objects. To detect clusters with diverse shapes and

sizes is a fundamental limitation of every clustering

algorithm. Even if we use the clustering criterion, the

discovery of a majority of the clusters present in the

data is a difficult goal while exploring the patterns.

This becomes more difficult when there is no much

information about the data organization.

1.2 Clustering and Classification

Clustering and Classification both are very

important for traditional pattern recognition and they

also complement each other. Clustering can improve

the generalization of classification while the

information from classes can improve the accuracy of

the clustering solutions.[1] To incorporate the

advantages of both these learning methods, many

algorithms have been developed. All these

approaches uses the method of optimizing clustering

criterion first and then the classification criterion

obtained in the clustering solution.

1.3 Applications of clustering gene expression data

Microarray technologies have been developed to

monitor expression levels of genes. Clustering

techniques proves to be helpful by giving insight to

features like gene function, gene structure, and

cellular processes [2]. Genes with similar expression

patterns called as co-expressed genes can be clustered

together with similar cellular functions. Moreover,

co-expressed genes in the same cluster are likely to

have same cellular processes. The inference of

regulation through the clustering of gene expression

data also gives details to information regarding the

mechanism of the transcriptional regulatory network.

Traditional Clustering Algorithms include

hierarchical, partitioning, and density-based methods.

International Journal of Computer Trends and Technology (IJCTT) volume 6 number 4 Dec 2013

ISSN: 2231-2803 http://www.ijcttjournal.org Page215

2. Hierarchical clustering

Hierarchical clustering generates a hierarchical

series of clusters which can be graphically

represented by a tree, termed as dendrogram. A

hierarchical clustering method can be started by

defining a distance between two data points in gene

expression. The groupings of two closest data points

are done and it proceeds to the creation of a cluster

tree. One way to evaluate whether the obtained

clusters are stable or not is to explore the original

data set and see whether the same clusters are found

again. Hierarchical clustering identifies sets of

correlated genes with same behavior present in the

samples and gives thousands of clusters in a tree like

structure which is difficult to understand and explore.

Hierarchical clustering can be further divided into

aggglometric and divisive based on the formation of

dendrogram.[3],[4]Agglomerative algorithms are

known to be bottom-up approach, which perform

repeated incorporations of groups of data until some

pre-defined threshold is reached. Here, linkage is

used as the criteria to determine the distance between

two clusters. Single linkage is the smallest minimum

distance between two objects of two clusters, and

complete linkage is the smallest maximum distance

between two objects of the two clusters whereas

average linkage is the mean distance between every

pair of objects of two clusters In agglometric

hierarchical clustering, all objects begin with

individual clusters .Then the object pair with highest

similarity is merged to the same cluster. Thus the

result of agglometric cluster is a complete graph

where each node has relations with all other nodes.

Divisive hierarchical clustering is contrary to

agglometric hierarchical clustering which uses top-

down approach. This approach recursively divide the

data until some pre-defined threshold is reached. The

algorithm divides the complete graph into smaller

components. It results in a dendogram with branches

as clusters and also provides the information about

the similarity between the clusters.

CURE [5] is one of the agglomerative

hierarchical clustering algorithms, which begins by

choosing a constant number, of well scattered points,

from a cluster. These points can be castoff to identify

the shape and size of the cluster. The next step of the

algorithm deals with the shrinkage of the selected

points toward the centroid of the cluster using some

predetermined fractional value. So this an

agglomerative hierarchical clustering algorithm,

relies on links and not distances, to measure the

proximity between a pair of data points, before the

merging is done. Some agglometric hierarchical

clustering like CHAMELEON [6], uses a graph

partitioning algorithm to partition based on the

nearest neighbor approach and then uses an

agglomerative hierarchical clustering algorithm to

combine the sub-clusters and after that find the real

clusters from them.

Hierarchical clustering methods are popular

because of their presentation of cluster results and are

preferred widely by biologists .This method has

many advantages in embedded flexibility regarding

the level of granularity and it is easy to handle any

forms of similarity or distance The method is

effective[3] which is depended on :

i. The appropriateness of the validity measure used.

ii. The need for incorporating information, expression

values and other type of biological domain

knowledge while exploring the cluster.

iii. Ability to be applied on high dimensional numeric

data.

iv. Representation of nested cluster structure is clear

but is unsatisfactory in representing intersected

clusters.

2. Partitional clustering

This Clustering technique uses the partitioning of

the available data points into different clusters based

on a single center criterion.

2.1 Centroid models

In many clustering algorithms, dissimilarity

between the points in datasets are computed using the

proximity distance measures like Euclidean distance,

Mahalanobis distance,Pearson correlation,etc. Some

algorithms have optimized validity measures like

compactness, separation or both of the clusters.

2.1.1 K-means

K-means [7] is a simple and fast centroid-based

clustering algorithm in which division of the data is

done based on pre-defined number of clusters in

order to optimize a predefined criterion. The K-

means algorithm calculates the center of a cluster by

using the mean of that cluster features [3] .The users

run the algorithm repeatedly with the use of different

values of k and compare the clustering results. Thus

the detection of the optimal number of clusters is

done. When a large gene expression dataset is

available, which consists of thousands of genes, this

extensive process may not be practical. Also, gene

expression data may normally contain a huge amount

of noise and the k-means algorithm forces each gene

to be included in a single cluster, which may lead to

the generation of biologically irrelevant clusters.

Here it becomes difficult to detect clusters of

arbitrary shapes and structure. Even though all these

difficulties prevail, the k-means algorithm is

International Journal of Computer Trends and Technology (IJCTT) volume 6 number 4 Dec 2013

ISSN: 2231-2803 http://www.ijcttjournal.org Page216

frequently used to cluster gene expression data due to

its simplicity and it provides baseline results when

compared to the development of new clustering

algorithms. The application of k-means algorithm and

its variants are widely used for clustering gene

expression data.

This algorithm is generally inefficient in the case

of categorical datasets which lack inherent distance

measure. Other extensions of K-means with cluster

medoids, cluster modes instead of cluster center were

also used. All these algorithms use a single function

for partitioning the data. In the cases where natural

ordering of entities is not found, algorithms like K-

means and fuzzy C-means fails.

2.1.2 K-medoids

A variation of K-means clustering method with

the cluster medoid taken as the most centrally located

point is termed as K-medoids. All the rest of the data

points are assigned to their clusters, based on the new

medoid determined in each iteration. Early versions

of k-medoid methods are the algorithms PAM and

CLARA [8]. PAM (Partitioning around Method) uses

dissimilarity values and an iterative approach to

determine a representative object for each cluster

called medoid. Once the medoids have been found,

each non-selected object is grouped with the medoid

to which it is found to be nearly similar. The quality

of a clustering is measured by the average

dissimilarity between an object and the medoid of its

cluster.

CLARA follows the same principle as PAM,

except in the approach of finding representative

objects for the entire dataset, instead it draws a

sample of the dataset, and applies PAM to this

sample. It then classifies the remaining objects using

usual partitioning principles. CLARANS [9]

functions on a randomized search of a graph to find

medoids which represents the clusters. The algorithm

takes input maxneighbor and numlocal, as input then

selects a random node and then tries to check a

sample of the neighbors of the particular node. If a

better neighbor is found, it moves to the neighbor and

continues the process until the maxneighbor criterion

is met. Otherwise, it declares the current node as a

local minimum and starts a new search for finding the

other local minima. After the collection of a specified

number of local minima or numlocal, the algorithm

returns the best of these local values as the medoid of

the cluster.

2.1.3 K-modes

K-modes [7] work in similar to K-medoids except

that instead of medoids, modes are used. This method

can be told as a version of fuzzy K-modes algorithm.

The steps are similar to K-medoids except in

assignment of cluster centers. K-modes is a much

faster extension of k-means algorithm to handle

categorical data which uses a different similarity

measure, as different from the case of k-means, k-

modes uses a frequency based method to update

modes. But the k-modes algorithm is useful only after

the conversion of the numeric data into categorical

data and may lead to information loss which

subsequently may deteriorate the cluster result.

All these traditional partitional clustering

techniques take the advantage of greedy search

techniques for the optimization of compactness of the

clusters. But these approaches suffer from the

problem of local optima and also only a single cluster

validity index is taken for optimization. Partitioning

based clustering algorithms can find separate clusters,

in the context of gene expression clustering,[3]but it

suffers from the following problems:

i. In the case where the number of clusters is not

known apriori.

ii. The validity measures used by most of the

above techniques are inadequate due to large size of

gene data.

iii. The gene data, apart from displaying disjoint

patterns of clusters, often show evidences of

intersected and embedded cluster patterns, which are

usually not encouraged.

3. DBSCAN

This is a density-based clustering algorithm. The

algorithm progresses with regions of high density

into clusters and discovers clusters of arbitrary shape

in spatial databases. It defines a cluster as a maximal

set of density-connected points. The given cluster

continues to grow as long as the density number of

objects or data points exceeds particular threshold. It

can be effectively used to filter out noise and

discover clusters of arbitrary shape. Statistically

significant patterns can be derived from dense

regions, which can then be used to identify genes of

interest and also eliminate others.

4. Soft Computing Techniques

4.1 Fuzzy partitioning

In classical fuzzy clustering, the fuzziness is

usually a possibility of membership of each element

into different classes with different degrees from [0,

1]. In this approach, fuzziness of clustering is

evaluated as the detail of the properties of classified

elements investigated. Sometimes Gene expression

data analysis encounters an intersecting gene pattern

in which case a crisp or hard clustering may not yield

International Journal of Computer Trends and Technology (IJCTT) volume 6 number 4 Dec 2013

ISSN: 2231-2803 http://www.ijcttjournal.org Page217

a good result. But for fuzzy clustering, a gene can

belong to several clusters with certain degrees of

membership.

4.1.1 Fuzzy C-means

Fuzzy C-means (FCM) [10] is a widely used

technique that uses the principles of fuzzy principles

to evolve a partition matrix.FCM algorithm starts

with randomly selected initial K cluster centers, and

then at every iteration it finds the fuzzy membership

of each gene. The main advantage of this algorithm is

that it has both the determination of initial clusters

and cluster validity, which are the fundamental stages

of a clustering process. Also it uses a more sensitive

accurate analysis compared to DBSCAN algorithm

since it uses the principles of the fuzzy theory. The

genetic algorithms (GAs) can be incorporated with

fuzzy clustering to produce a better cluster. In the

approach of GA-based fuzzy clusters, real numbers

represent the data points of the centers of the

partitions.

5. Gene Expression Patterns and Clustering

The study of expression levels of genes can be

done with the advancement in the field of microarray

technology. This technology finds its application in

various fields including medical diagnosis of

diseases. The analysis of microarray data can be done

by clustering.[11]While considering the set of

features in the clustering process, most of the existing

clustering algorithms appears to be sensitive.

5.1.1 Single objective clustering

Any external knowledge is unavailable during the

process of clustering and they are generally

unsupervised. In single objective clustering method,

the criterion may be based on the similarity or

dissimilarity of the data items[12].The clusters

formed by these criterion may not be correct as they

can take more other complex structures and the

clusters can fail if the chosen objective function is not

appropriate.

5.1.2 Multiobjective Clustering

In Multiobjective clustering, we use several

clustering algorithms along with different objective

functions. The result may not only contain the

clusters, but also the specific objective function

contributing towards the cluster formation[13].Here

the problem of choosing one objective function as in

single objective function is alleviated as this

approach uses the combination of different objective

functions.

6. Evolutionary methods

A genetic algorithm (or GA) is a search technique

used to find true and approximate solutions to

optimization and search problems. Genetic

algorithms are categorized as global search

techniques.[14]These are a particular class of

evolutionary algorithms that use techniques inspired

by evolutionary biology such as inheritance,

mutation, selection, and crossover. The Single

objective Genetic Algorithm uses the approach of

using a single function with different clustering

algorithms. In this clustering technique, each

algorithm works with separate individual functions

such that the result has cluster solution with unique

functions different from other clusters.

7. Challenges of gene clustering

Special characteristics of gene expression data,

and the particular requirements from the biological

domain, gene-based clustering presents several new

challenges [3][2].

First, cluster analysis is typically the first step in data

mining and knowledge discovery. The purpose of

clustering gene expression data is to reveal the

natural data structures and gain some initial insights

regarding data distribution. Therefore, a good

clustering algorithm should depend as little as

possible on prior knowledge, which is usually not

available before cluster analysis.

Second, the effectiveness of a clustering technique is

highly influenced by the proximity measure, used by

the technique. Choosing or finding such an

appropriate proximity measure is a challenging task.

Third, gene expression data often contain a huge

amount of noise and missing values, due to the

complex procedures of microarray experiments.

Therefore, clustering algorithms for gene expression

data should be capable of extracting useful and

needed information.

Fourth, algorithms for gene-based clustering should

be able to effectively handle the situation that gene

expression data are highly connected, and clusters

may be highly intersected with each other or even

embedded.

Finally, the associations between the clusters and also

the relationship between the genes within the same

cluster are of great importance. Thus the clustering

algorithm should not only partition the data set but

also provide some graphical representation of the

cluster structure would be more efficient. Also,

clustering algorithm should be efficient in order to

scale with the increasing size of datasets as well as

dimensionality.

International Journal of Computer Trends and Technology (IJCTT) volume 6 number 4 Dec 2013

ISSN: 2231-2803 http://www.ijcttjournal.org Page218

Conclusion

Although gene expression clustering has been done

by applying k-means, hierarchical clustering and

DBSCANS, the desired features for clustering can

include the minimum user input for finding arbitrary

shaped clusters, robustness to noises and the ability to

handle higher dimensionality data. If outliers or

noises create a problem, a new technique is suitable

for outlier detection if hierarchical clustering is to be

used. Fuzzy C-means or GA based approach supports

overlapping clusters of co-regulated genes and needs

user specified parameters. A clustering algorithms

capability to cluster biological data set depends upon

certain desirable features such as speed, minimum

number of input parameters, robustness to noise and

outliers. Though the principles of many clustering

algorithms available satisfy these requirements, in

most cases, they do not provide accurate solutions

and cannot be applied for clustering of biological

data.

In this assessment, an attempt has been made to

provide a comprehensive and precise survey of

various clustering approaches in the context of

pattern identification and recognition in the gene

expression data. Effectiveness of a clustering

technique is highly influenced by the selection of

algorithm and criterion used by the technique. A

short list of clustering approaches available for

numeric data clustering is provided. Each algorithm

is analyzed effectively and their shortcomings are

also enumerated. Finally, discussion about the

challenges faced by the clustering schemes available

for the effective clustering of gene expression is also

provided.

Acknowledgement

I feel it pleasure to be indebted to my guide Mr Mathew Kurian,

M.E, Assistant professor, Department of Computer Science and

Engineering for his invaluable support, advice and encouragement

and the reference for his feedback.

References

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Multiobjective Simultaneous Learning Framework for Clustering

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