Abstract: Data mining technique used in the field of clustering is a subject of active research and assists in biological pattern recognition and extraction of new knowledge from raw data. Clustering means the act of partitioning an unlabeled dataset into groups of similar objects. Each group, called a cluster, consists of objects that are similar between themselves and dissimilar to objects of other groups. Several clustering methods are based on partitional clustering. This category attempts to directly decompose the dataset into a set of disjoint clusters leading to an integer number of clusters that optimizes a given criterion function. The criterion function may emphasize a local or a global structure of the data, and its optimization is an iterative relocation procedure. The K-Means algorithm is one of the most widely used partitional clustering techniques. Since K-Means is extremely sensitive to the initial choice of centers and a poor choice of centers may lead to a local optimum that is quite inferior to the global optimum, we propose a strategy to initiate K-Means centers. The improved K-Means algorithm is compared with the original K-Means, and the results prove how the efficiency has been significantly improved.
Abstract: Endothelial Progenitor Cell (EPC) based therapies continue to be of interest to treat ischemic events based on their proven role to promote blood vessel formation and thus tissue re-vascularisation. Current strategies for the production of clinical-grade EPCs requires the in vitro isolation of EPCs from peripheral blood followed by cell expansion to provide sufficient quantities EPCs for cell therapy. This study aims to examine the use of different biomolecules to significantly improve the current strategy of EPC capture and expansion on collagen type I (Col I). In this study, four different biomolecules were immobilised on a surface and then investigated for their capacity to support EPC capture and proliferation. First, a cell microarray platform was fabricated by coating a glass surface with epoxy functional allyl glycidyl ether plasma polymer (AGEpp) to mediate biomolecule binding. The four candidate biomolecules tested were Col I, collagen type II (Col II), collagen type IV (Col IV) and vascular endothelial growth factor A (VEGF-A), which were arrayed on the epoxy-functionalised surface using a non-contact printer. The surrounding area between the printed biomolecules was passivated with polyethylene glycol-bisamine (A-PEG) to prevent non-specific cell attachment. EPCs were seeded onto the microarray platform and cell numbers quantified after 1 h (to determine capture) and 72 h (to determine proliferation). All of the extracellular matrix (ECM) biomolecules printed demonstrated an ability to capture EPCs within 1 h of cell seeding with Col II exhibiting the highest level of attachment when compared to the other biomolecules. Interestingly, Col IV exhibited the highest increase in EPC expansion after 72 h when compared to Col I, Col II and VEGF-A. These results provide information for significant improvement in the capture and expansion of human EPC for further application.
Abstract: Prediction of perturbations after genetic manipulation
(especially gene knockout) is one of the important challenges in
systems biology. In this paper, a new algorithm is introduced that
integrates microarray data into the metabolic model. The algorithm
was used to study the change in the cell phenotype after knockout of
Gss gene in Escherichia coli BW25113. Algorithm implementation
indicated that gene deletion resulted in more activation of the
metabolic network. Growth yield was more and less regulating gene
were identified for mutant in comparison with the wild-type strain.
Abstract: Feature Selection is significant in order to perform constructive classification in the area of cancer diagnosis. However, a large number of features compared to the number of samples makes the task of classification computationally very hard and prone to errors in microarray gene expression datasets. In this paper, we present an innovative method for selecting highly informative gene subsets of gene expression data that effectively classifies the cancer data into tumorous and non-tumorous. The hybrid gene selection technique comprises of combined Mutual Information and Fisher score to select informative genes. The gene selection is validated by classification using Support Vector Machine (SVM) which is a supervised learning algorithm capable of solving complex classification problems. The results obtained from improved Mutual Information and F-Score with SVM as a classifier has produced efficient results.
Abstract: In recent years, there has been an explosion in the rate of using technology that help discovering the diseases. For example, DNA microarrays allow us for the first time to obtain a "global" view of the cell. It has great potential to provide accurate medical diagnosis, to help in finding the right treatment and cure for many diseases. Various classification algorithms can be applied on such micro-array datasets to devise methods that can predict the occurrence of Leukemia disease. In this study, we compared the classification accuracy and response time among eleven decision tree methods and six rule classifier methods using five performance criteria. The experiment results show that the performance of Random Tree is producing better result. Also it takes lowest time to build model in tree classifier. The classification rules algorithms such as nearest- neighbor-like algorithm (NNge) is the best algorithm due to the high accuracy and it takes lowest time to build model in classification.
Abstract: A DNA microarray technology is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome. Elucidating the patterns hidden in gene expression data offers a tremendous opportunity for an enhanced understanding of functional genomics. However, the large number of genes and the complexity of biological networks greatly increase the challenges of comprehending and interpreting the resulting mass of data, which often consists of millions of measurements. It is handled by clustering which reveals the natural structures and identifying the interesting patterns in the underlying data. In this paper, gene based clustering in gene expression data is proposed using Cuckoo Search with Differential Evolution (CS-DE). The experiment results are analyzed with gene expression benchmark datasets. The results show that CS-DE outperforms CS in benchmark datasets. To find the validation of the clustering results, this work is tested with one internal and one external cluster validation indexes.
Abstract: As DNA microarray data contain relatively small
sample size compared to the number of genes, high dimensional
models are often employed. In high dimensional models, the selection
of tuning parameter (or, penalty parameter) is often one of the crucial
parts of the modeling. Cross-validation is one of the most common
methods for the tuning parameter selection, which selects a parameter
value with the smallest cross-validated score. However, selecting a
single value as an ‘optimal’ value for the parameter can be very
unstable due to the sampling variation since the sample sizes of
microarray data are often small. Our approach is to choose multiple candidates of tuning parameter
first, then average the candidates with different weights depending
on their performance. The additional step of estimating the weights
and averaging the candidates rarely increase the computational cost,
while it can considerably improve the traditional cross-validation. We
show that the selected value from the suggested methods often lead to
stable parameter selection as well as improved detection of significant
genetic variables compared to the tradition cross-validation via real
data and simulated data sets.
Abstract: Array-based gene expression analysis is a powerful
tool to profile expression of genes and to generate information on
therapeutic effects of new anti-cancer compounds. Anti-apoptotic
effect of thymoquinone was studied in MCF7 breast cancer cell line
using gene expression profiling with cDNA microarray. The purity
and yield of RNA samples were determined using RNeasyPlus Mini
kit. The Agilent RNA 6000 NanoLabChip kit evaluated the quantity
of the RNA samples. AffinityScript RT oligo-dT promoter primer
was used to generate cDNA strands. T7 RNA polymerase was used to
convert cDNA to cRNA. The cRNA samples and human universal
reference RNA were labelled with Cy-3-CTP and Cy-5-CTP,
respectively. Feature Extraction and GeneSpring softwares analysed
the data. The single experiment analysis revealed involvement of 64
pathways with up-regulated genes and 78 pathways with downregulated
genes. The MAPK and p38-MAPK pathways were
inhibited due to the up-regulation of PTPRR gene. The inhibition of
p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of
p38-MAPK caused up-regulation of TP53 and down-regulation of
Bcl2 genes indicating involvement of intrinsic apoptotic pathway.
Down-regulation of CARD16 gene as an adaptor molecule regulated
CASP1 and suggested necrosis-like programmed cell death and
involvement of caspase in apoptosis. Furthermore, down-regulation
of GPCR, EGF-EGFR signalling pathways suggested reduction of
ER. Involvement of AhR pathway which control cytochrome P450
and glucuronidation pathways showed metabolism of Thymoquinone.
The findings showed differential expression of several genes in
apoptosis pathways with thymoquinone treatment in estrogen
receptor-positive breast cancer cells.
Abstract: Development of a method to estimate gene functions is
an important task in bioinformatics. One of the approaches for the
annotation is the identification of the metabolic pathway that genes are
involved in. Since gene expression data reflect various intracellular
phenomena, those data are considered to be related with genes’
functions. However, it has been difficult to estimate the gene function
with high accuracy. It is considered that the low accuracy of the
estimation is caused by the difficulty of accurately measuring a gene
expression. Even though they are measured under the same condition,
the gene expressions will vary usually. In this study, we proposed a
feature extraction method focusing on the variability of gene
expressions to estimate the genes' metabolic pathway accurately. First,
we estimated the distribution of each gene expression from replicate
data. Next, we calculated the similarity between all gene pairs by KL
divergence, which is a method for calculating the similarity between
distributions. Finally, we utilized the similarity vectors as feature
vectors and trained the multiclass SVM for identifying the genes'
metabolic pathway. To evaluate our developed method, we applied the
method to budding yeast and trained the multiclass SVM for
identifying the seven metabolic pathways. As a result, the accuracy
that calculated by our developed method was higher than the one that
calculated from the raw gene expression data. Thus, our developed
method combined with KL divergence is useful for identifying the
genes' metabolic pathway.
Abstract: Analyzing DNA microarray data sets is a great
challenge, which faces the bioinformaticians due to the complication
of using statistical and machine learning techniques. The challenge
will be doubled if the microarray data sets contain missing data,
which happens regularly because these techniques cannot deal with
missing data. One of the most important data analysis process on
the microarray data set is feature selection. This process finds the
most important genes that affect certain disease. In this paper, we
introduce a technique for imputing the missing data in microarray
data sets while performing feature selection.
Abstract: Microarray technology is universally used in the study
of disease diagnosis using gene expression levels. The main
shortcoming of gene expression data is that it includes thousands of
genes and a small number of samples. Abundant methods and
techniques have been proposed for tumor classification using
microarray gene expression data. Feature or gene selection methods
can be used to mine the genes that directly involve in the
classification and to eliminate irrelevant genes. In this paper
statistical measures like T-Statistics, Signal-to-Noise Ratio (SNR)
and F-Statistics are used to rank the genes. The ranked genes are used
for further classification. Particle Swarm Optimization (PSO)
algorithm and Shuffled Frog Leaping (SFL) algorithm are used to
find the significant genes from the top-m ranked genes. The Naïve
Bayes Classifier (NBC) is used to classify the samples based on the
significant genes. The proposed work is applied on Lung and Ovarian
datasets. The experimental results show that the proposed method
achieves 100% accuracy in all the three datasets and the results are
compared with previous works.
Abstract: Microarray gene expression data play a vital in biological processes, gene regulation and disease mechanism. Biclustering in gene expression data is a subset of the genes indicating consistent patterns under the subset of the conditions. Finding a biclustering is an optimization problem. In recent years, swarm intelligence techniques are popular due to the fact that many real-world problems are increasingly large, complex and dynamic. By reasons of the size and complexity of the problems, it is necessary to find an optimization technique whose efficiency is measured by finding the near optimal solution within a reasonable amount of time. In this paper, the algorithmic concepts of the Particle Swarm Optimization (PSO), Shuffled Frog Leaping (SFL) and Cuckoo Search (CS) algorithms have been analyzed for the four benchmark gene expression dataset. The experiment results show that CS outperforms PSO and SFL for 3 datasets and SFL give better performance in one dataset. Also this work determines the biological relevance of the biclusters with Gene Ontology in terms of function, process and component.
Abstract: Microarrays are made it possible to simultaneously monitor the expression profiles of thousands of genes under various experimental conditions. It is used to identify the co-expressed genes in specific cells or tissues that are actively used to make proteins. This method is used to analysis the gene expression, an important task in bioinformatics research. Cluster analysis of gene expression data has proved to be a useful tool for identifying co-expressed genes, biologically relevant groupings of genes and samples. In this work K-Means algorithms has been applied for clustering of Gene Expression Data. Further, rough set based Quick reduct algorithm has been applied for each cluster in order to select the most similar genes having high correlation. Then the ACV measure is used to evaluate the refined clusters and classification is used to evaluate the proposed method. They could identify compact clusters with feature selection method used to genes are selected.
Abstract: The DNA microarray technology concurrently monitors the expression levels of thousands of genes during significant biological processes and across the related samples. The better understanding of functional genomics is obtained by extracting the patterns hidden in gene expression data. It is handled by clustering which reveals natural structures and identify interesting patterns in the underlying data. In the proposed work clustering gene expression data is done through an Advanced Nelder Mead (ANM) algorithm. Nelder Mead (NM) method is a method designed for optimization process. In Nelder Mead method, the vertices of a triangle are considered as the solutions. Many operations are performed on this triangle to obtain a better result. In the proposed work, the operations like reflection and expansion is eliminated and a new operation called spread-out is introduced. The spread-out operation will increase the global search area and thus provides a better result on optimization. The spread-out operation will give three points and the best among these three points will be used to replace the worst point. The experiment results are analyzed with optimization benchmark test functions and gene expression benchmark datasets. The results show that ANM outperforms NM in both benchmarks.
Abstract: Identification of cancer genes that might anticipate
the clinical behaviors from different types of cancer disease is
challenging due to the huge number of genes and small number of
patients samples. The new method is being proposed based on
supervised learning of classification like support vector machines
(SVMs).A new solution is described by the introduction of the
Maximized Margin (MM) in the subset criterion, which permits to
get near the least generalization error rate. In class prediction
problem, gene selection is essential to improve the accuracy and to
identify genes for cancer disease. The performance of the new
method was evaluated with real-world data experiment. It can give
the better accuracy for classification.
Abstract: Inferring the network structure from time series data
is a hard problem, especially if the time series is short and noisy.
DNA microarray is a technology allowing to monitor the mRNA
concentration of thousands of genes simultaneously that produces
data of these characteristics. In this study we try to investigate the
influence of the experimental design on the quality of the result.
More precisely, we investigate the influence of two different types of
random single gene perturbations on the inference of genetic networks
from time series data. To obtain an objective quality measure for
this influence we simulate gene expression values with a biologically
plausible model of a known network structure. Within this framework
we study the influence of single gene knock-outs in opposite to
linearly controlled expression for single genes on the quality of the
infered network structure.
Abstract: The most important property of the Gene Ontology is
the terms. These control vocabularies are defined to provide
consistent descriptions of gene products that are shareable and
computationally accessible by humans, software agent, or other
machine-readable meta-data. Each term is associated with
information such as definition, synonyms, database references, amino
acid sequences, and relationships to other terms. This information has
made the Gene Ontology broadly applied in microarray and
proteomic analysis. However, the process of searching the terms is
still carried out using traditional approach which is based on keyword
matching. The weaknesses of this approach are: ignoring semantic
relationships between terms, and highly depending on a specialist to
find similar terms. Therefore, this study combines semantic similarity
measure and genetic algorithm to perform a better retrieval process
for searching semantically similar terms. The semantic similarity
measure is used to compute similitude strength between two terms.
Then, the genetic algorithm is employed to perform batch retrievals
and to handle the situation of the large search space of the Gene
Ontology graph. The computational results are presented to show the
effectiveness of the proposed algorithm.
Abstract: A dissimilarity measure between the empiric
characteristic functions of the subsamples associated to the different
classes in a multivariate data set is proposed. This measure can be
efficiently computed, and it depends on all the cases of each class. It
may be used to find groups of similar classes, which could be joined
for further analysis, or it could be employed to perform an
agglomerative hierarchical cluster analysis of the set of classes. The
final tree can serve to build a family of binary classification models,
offering an alternative approach to the multi-class SVM problem. We
have tested this dendrogram based SVM approach with the oneagainst-
one SVM approach over four publicly available data sets,
three of them being microarray data. Both performances have been
found equivalent, but the first solution requires a smaller number of
binary SVM models.
Abstract: Segmentation, filtering out of measurement errors and
identification of breakpoints are integral parts of any analysis of
microarray data for the detection of copy number variation (CNV).
Existing algorithms designed for these tasks have had some successes
in the past, but they tend to be O(N2) in either computation time or
memory requirement, or both, and the rapid advance of microarray
resolution has practically rendered such algorithms useless. Here we
propose an algorithm, SAD, that is much faster and much less thirsty
for memory – O(N) in both computation time and memory requirement
-- and offers higher accuracy. The two key ingredients of SAD are the
fundamental assumption in statistics that measurement errors are
normally distributed and the mathematical relation that the product of
two Gaussians is another Gaussian (function). We have produced a
computer program for analyzing CNV based on SAD. In addition to
being fast and small it offers two important features: quantitative
statistics for predictions and, with only two user-decided parameters,
ease of use. Its speed shows little dependence on genomic profile.
Running on an average modern computer, it completes CNV analyses
for a 262 thousand-probe array in ~1 second and a 1.8 million-probe
array in 9 seconds
Abstract: Analysis and visualization of microarraydata is veryassistantfor biologists and clinicians in the field of diagnosis and treatment of patients. It allows Clinicians to better understand the structure of microarray and facilitates understanding gene expression in cells. However, microarray dataset is a complex data set and has thousands of features and a very small number of observations. This very high dimensional data set often contains some noise, non-useful information and a small number of relevant features for disease or genotype. This paper proposes a non-linear dimensionality reduction algorithm Local Principal Component (LPC) which aims to maps high dimensional data to a lower dimensional space. The reduced data represents the most important variables underlying the original data. Experimental results and comparisons are presented to show the quality of the proposed algorithm. Moreover, experiments also show how this algorithm reduces high dimensional data whilst preserving the neighbourhoods of the points in the low dimensional space as in the high dimensional space.