Engineering, 2013, 5, 549-552
http://dx.doi.org/10.4236/eng.2013.510B113 Published Online October 2013 (http://www.scirp.org/journal/eng)
Copyright © 2013 SciRes. ENG
On Clustering Algorithms for B iological Data*
Xiaowan Li, Fei Zhu#
School of Computer Science and Technology, Soochow University, Suzhou, China
Email: firstname.lastname@example.org, #email@example.com
Age of knowledge explosion requires us not only to have the ability to get useful information which represented by data
but also to find knowledg e in information. Human Genome Project achieved large amount of such biologica l data, and
people foun d clustering is a promising approach to analyze those biological data for knowledge hidden. The researches
on biological data go to in-depth gradually and so are the clustering algorithms. This article mainly introduces current
broad-used clustering algo rithms, including the main idea, improvements, key technology, advantage and disadvantage,
and the applications in biological field as well as the problems they solve. What’s more, this article roughly introduces
some database used in biological field.
Keywords: Clustering; Algorithms; Biologiocal Data; Applications ; Database
We humans are now in an era of information which are
stored or represented as data. People have found that it is
an effective way to classify or group things into a set of
categories or clusters in order to analyze them. Because
when encountering new things, we always try to seek
features that can describe them by comparing them with
objects we already knew and things in the same cluster
because things in one clustering always share similar
features and have similar functions. And data reflect
those features and functions. So we can cluster data to
analyze further knowledg e . What’s more, things are not
single or isolated but have verities of links. So when the
number of objects gets bigger the relationship will be-
come more complex. It will be easier to analyze high
connected things other than a s i ngle one.
So clustering is a promising way to analyze biological
data. From one hand, biological data contains large
amount of knowledge which may be unknown but useful.
However the quantity and complexity of biological data
make it hard to analyze those data in a certain study for
that knowledge. So we need to cluster them first to sim-
plify the process. From other hand, biological function is
not determined by a single gene or protein. There are
complex relationships to consider, we should analyze
data in high connected subgraphs.
Different clustering a lgorithms are designed on th e ba-
sis of different applications to solve different problems.
Some of them proved to be good in biological field by
achieving good results or accelerating the process. In the
meantime, with the research on biological field goes
in-depth, clustering algorithms are improved to favor the
new need .
2. Conventional Clustering Algorithms
2.1. Hierarchical Clusterin g Algorithm
There are two of Hierarchical Clustering Algorithms,
AGNES and DIA NA .
AGNES: Make every object a single cluster and then
merge the nearest two, refresh the distance of the original
and new one, then repeat it until all of objects are one
cluster or reach the result wanted.
DIANA: Make all objects one then divide it, until
every objects is a single cluster or reach the result
Step4 Step3 Step2 Step1 step0
*This work is supported by fund NO.5731512811. This work is super-
vised by Fei Zhu.
X. W. LI, F. ZHU
Copyright © 2013 SciRes. ENG
The hierarchical clustering algorithm is used frequent-
ly because it is simple and it can handle large data. But it
has high compute and complex calculates and the data's
class cannot be adjusted once settled.
Liming Wang and Xiaodong Wang propose a non-
parametric Bayesian clustering algorithm based on the
hierarchical Dirichlet processes (HDP) which capture the
hierarchical features prevalent in biological data. They
conduct experiments on the yeast galactose datasets and
yeast cell cycle datasets by comparing their clustering
results to the standard results. The proposed clustering
algorithm is shown to outperform several popular clus-
tering algorithms by revealing the underlying hierarchic-
al structure of the data .
2.2. Fuzzy Clustering Algorithms
Classification problem in practice is often fuzzy and
many papers prove that fuzzy clustering algorithm is an
effective tool for the analysis of biological data [4,5].
FCM: 1974, Dunn proposed this algorithm, and Bez-
dek promoted it. The standard FCM as follows, in which
the Euclidean or L2 norm distance function is used .
1) Select appropriate values for m, c, and a small posi-
Number c. Initialize the prototype matrix M ran domly.
Set step variable t = 0.
2) Calculate (at t = 0) or update (at t > 0) t he me mber -
ship Matrix U by
for i = 1, ··· c and j = 1, ··· N.
3) Update the prototype matrix M by
for i = 1,…c.
4) Repeat steps 2)-3) until
FCM algorithm and other visions of it are robust to the
scaling transformation of dataset, while others are sensi-
tive to such transformation . So they are used widely.
Compared with K-means, it is more efficient for the
needless of iteration. But it has a problem of being easily
influenced by isolated points, and it has difficulties of
determining cl us t e r i ng numbe r .
2.3. Graph Clustering Algorithm
In the post-genome era, it is a current challenge to mine
the hidden knowledge stored in the biological networks
. As an important means for knowledge discovery,
graph clustering does better in the analysis of complex
biological networks .
The advantage of graph clu s tering is that it is relatively
straight forward to see the highly connected subgraphs
because of the network community structure.
However there are some problems remain to be solved.
For example, some of these complex networks have so
many nodes that it is difficult to compute effectively.
What's more, many typical networks have high in homo-
geneity, which will make graph clustering algorithm lose
Jain created the main idea of graph clustering algo-
rithm that made a minimal spanning tree (MST) about
data, and then delete the longest branch of the minimum
tree to cluster. The main algorithms include Random,
Walk, CHAMELEON and AUTOCLUST.
3. Biological Applications
• Two clustering algorithms are used by Jing Yang to
analyze the data searched from the Nucleotide data-
base of National Center for Biotechnology Informa-
tion (NCBI) and they have similar results, which
could give big support on study of PD (Parkinson's
• Based on the aiNer model an important model of Ar-
tificial Immune System Jun Wang and Xinyu Liu
presented aiNHA. This algorithm can be used in
clustering the arbitrary shapes of data sets with fast
discovering speed high efficiency , and ins e ns i-
tive about noise.
• Gene Ontology (GO), a novel and effective method
named significant clustering analysis based on GO
(ScaGO) was presented to improve individual GO
term analysis algorithm for detecting differential gene
expression. Compared to individual GO term analysis,
ScaGO was turned out to be more sensitive when ap-
plied to the acute lymphoblastic leukemia expression
dataset and yeast Rapl DNA-binding mutant dataset,
and some novel differential expression changes which
were mostly reported were mined successfully .
• Juan Men came up with a high-performed graph clus-
tering algorithm: CD (contraction-dilation), which can
be applied to analyze large networks. This algorithm
focu sing on complex biological networks is proved to
be efficient to discover more stable community struc-
tures with higher modularity scores and accuracies at
lower expenses of both CPU time and memory. CD is
superior to spectral clustering algorithm and MCL
algorithm because it can detect protein remote ho-
mology successfully at the meantime. The results
show that sequence similarity carry significant infor-
mation on remote homology, which can be mined by
using CD algorithm.
• Yuan Wei and Zhu Shanfeng clarify problems of cur-
rent clustering method by analyzing their reliability
X. W. LI, F. ZHU
Copyright © 2013 SciRes. ENG
and parameters, and put forward a solution: ensemble
clustering. And they use Mesh ontology as knowledge
to improve the clustering, which contains a wealth of
knowledge of biology. This algorithm based on the
distance between the MeSH is proved to be better in
clustering results compared with other methods .
• Yuan Yinli proposed a revised fuzzy algorithm to
solve the problem that it is difficult to select hidden
node centers in the study of RBF network. And ap-
plied it to strengthen the robustness of the outliers by
the network with the effectiveness proved .
• Cuifang GAO proposed a new algorithms: CKFCM
(collaborative kernel fuzzy c-means clustering), in
which the function of collaborative relationship was
incorporated into kemel fuzzy c-means clustering
(KFCM). By enlarging the difference among the sam-
ples and implementing on several subsets can be pro-
cessed together with an objective function, CKFCM
achieves better classification and is effective cluster-
ing with better per formance .
• An improved algorithm of weighted fuzzy kemel
clustering (WFKCA) is proposed to overcome its
shortcoming of liability to stick to local optimum. To
reduce the possibility of local optimum the idea of
iterative self-organizing data analysis techniques al-
gorithm (ISOODATA) is introduced into the WFKCA,
and initial center vectors are adjusted by the interme-
diate results from splitting and/or merging of cluster-
ing centers. It achieves more stable performance of
clustering for using match-able measurement from
feature space, and increases the adjustment range of
clustering centers .
• Damodar Reddy Edla and Prasanta K. Janawe pro-
pose a new clustering algorithm which is based on
Voronoi diagram. The algorithm uses a real valued
function defined by the radii of Voronoi circles. This
function enables to deal with the inner points of the
clusters followed by the boundary points. The pro-
posed scheme is applied on various artificial and bio-
logical data. The experimental results of the proposed
method are also compared with K-means and a few
existing clustering techn iques .
• Take noise into account, there are several means to
deal with it. For example, Roman Sloutsky, Nicolas
Jimenez, S. Joshua Swamidass and Kristen M. Naegle
explore several methods of accounting for noise when
analyzing biological data sets through clustering .
4. Introductions to Bioinformatics Databases
• GenBank: A complete database of DNA sequences
contains almost all of the Protein sequences and DNA
sequences that have been found as well as the relative
paper. Each data record has a simple description, such
as scientific name, references, table of the feature and
the sequence itself.
• GDB: preserve and deal with the gene data for Hu-
man Genome Project, contains the human genome re-
gion, the human genome map and the genetic varia-
tion. It provides read or write access directly.
• PIR and PSD: An overall, annotated, no redundant
database for protein sequence, including some protein
sequences come from dozens of integrated genes.
Thus, almost 99% of the data have been classified in
a certain protein family. And cross-reference can be
achieved in the annotation.
• COG: Attempt on a phylogenetic classification of the
proteins encoded in 21 complete genomes of bacteria,
archaea and eukaryotes, constructed by applying the
criterion of consistency of genome-specific best hits
to the results of an exhaustive comparison of all pro-
tein sequences from these genomes. The database
comprises 2091 COGs that include 56% - 83% of the
gene produc t s from each of the complete bacterial and
archaeal genomes and ~35% of those from the yeast
Saccharomyces cerevisiae genome .
From the introd uction we can know that every clustering
algorithm has advantages, disadvantages and scope of
application. So it is necessary to analyze each clustering
algorithm to use them better. Thus the truth is that it is
useful to apply clustering algorithms on biological data.
What’s more, the deeper the research goes, the higher the
demand becomes. So we should also analyze each case to
know the exact requirement for the algorithms and then
improve the current algorithm to get a better result.
Xiaowan LI, ID Number: 1027401004, currently is an
undergraduate student of Computer Science and Tech-
nology School of Soochow University, majoring in com-
puter science and technology.
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