Abstract: An evolutionary method whose selection and recombination
operations are based on generalization error-bounds of
support vector machine (SVM) can select a subset of potentially
informative genes for SVM classifier very efficiently [7]. In this
paper, we will use the derivative of error-bound (first-order criteria)
to select and recombine gene features in the evolutionary process,
and compare the performance of the derivative of error-bound with
the error-bound itself (zero-order) in the evolutionary process. We
also investigate several error-bounds and their derivatives to compare
the performance, and find the best criteria for gene selection
and classification. We use 7 cancer-related human gene expression
datasets to evaluate the performance of the zero-order and first-order
criteria of error-bounds. Though both criteria have the same strategy
in theoretically, experimental results demonstrate the best criterion
for microarray gene expression data.
Abstract: The goal of Gene Expression Analysis is to understand the processes that underlie the regulatory networks and pathways controlling inter-cellular and intra-cellular activities. In recent times microarray datasets are extensively used for this purpose. The scope of such analysis has broadened in recent times towards reconstruction of gene networks and other holistic approaches of Systems Biology. Evolutionary methods are proving to be successful in such problems and a number of such methods have been proposed. However all these methods are based on processing of genotypic information. Towards this end, there is a need to develop evolutionary methods that address phenotypic interactions together with genotypic interactions. We present a novel evolutionary approach, called Phenomic algorithm, wherein the focus is on phenotypic interaction. We use the expression profiles of genes to model the interactions between them at the phenotypic level. We apply this algorithm to the yeast sporulation dataset and show that the algorithm can identify gene networks with relative ease.
Abstract: Oxidative stress is considered to be the cause for onset
and the progression of type 2 diabetes mellitus (T2DM) and
complications including neuropathy. It is a deleterious process that
can be an important mediator of damage to cell structures: protein,
lipids and DNA. Data suggest that in patients with diabetes and
diabetic neuropathy DNA repair is impaired, which prevents effective
removal of lesions. Objective: The aim of our study was to evaluate
the association of the hOGG1 (326 Ser/Cys) and XRCC1 (194
Arg/Trp, 399 Arg/Gln) gene polymorphisms whose protein is
involved in the BER pathway with DNA repair efficiency in patients
with diabetes type 2 and diabetic neuropathy compared to the healthy
subjects. Genotypes were determined by PCR-RFLP analysis in 385
subjects, including 117 with type 2 diabetes, 56 with diabetic
neuropathy and 212 with normal glucose metabolism. The
polymorphisms studied include codon 326 of hOGG1 and 194, 399
of XRCC1 in the base excision repair (BER) genes. Comet assay was
carried out using peripheral blood lymphocytes from the patients and
controls. This test enabled the evaluation of DNA damage in cells
exposed to hydrogen peroxide alone and in the combination with the
endonuclease III (Nth). The results of the analysis of polymorphism
were statistically examination by calculating the odds ratio (OR) and
their 95% confidence intervals (95% CI) using the ¤ç2-tests. Our data
indicate that patients with diabetes mellitus type 2 (including those
with neuropathy) had higher frequencies of the XRCC1 399Arg/Gln
polymorphism in homozygote (GG) (OR: 1.85 [95% CI: 1.07-3.22],
P=0.3) and also increased frequency of 399Gln (G) allele (OR: 1.38
[95% CI: 1.03-1.83], P=0.3). No relation to other polymorphisms
with increased risk of diabetes or diabetic neuropathy. In T2DM
patients complicated by neuropathy, there was less efficient repair of
oxidative DNA damage induced by hydrogen peroxide in both the
presence and absence of the Nth enzyme. The results of our study
suggest that the XRCC1 399 Arg/Gln polymorphism is a significant
risk factor of T2DM in Polish population. Obtained data suggest a
decreased efficiency of DNA repair in cells from patients with
diabetes and neuropathy may be associated with oxidative stress.
Additionally, patients with neuropathy are characterized by even
greater sensitivity to oxidative damage than patients with diabetes,
which suggests participation of free radicals in the pathogenesis of
neuropathy.
Abstract: Yeast cells live in a constantly changing environment that requires the continuous adaptation of their genomic program in order to sustain their homeostasis, survive and proliferate. Due to the advancement of high throughput technologies, there is currently a large amount of data such as gene expression, gene deletion and protein-protein interactions for S. Cerevisiae under various environmental conditions. Mining these datasets requires efficient computational methods capable of integrating different types of data, identifying inter-relations between different components and inferring functional groups or 'modules' that shape intracellular processes. This study uses computational methods to delineate some of the mechanisms used by yeast cells to respond to environmental changes. The GRAM algorithm is first used to integrate gene expression data and ChIP-chip data in order to find modules of coexpressed and co-regulated genes as well as the transcription factors (TFs) that regulate these modules. Since transcription factors are themselves transcriptionally regulated, a three-layer regulatory cascade consisting of the TF-regulators, the TFs and the regulated modules is subsequently considered. This three-layer cascade is then modeled quantitatively using artificial neural networks (ANNs) where the input layer corresponds to the expression of the up-stream transcription factors (TF-regulators) and the output layer corresponds to the expression of genes within each module. This work shows that (a) the expression of at least 33 genes over time and for different stress conditions is well predicted by the expression of the top layer transcription factors, including cases in which the effect of up-stream regulators is shifted in time and (b) identifies at least 6 novel regulatory interactions that were not previously associated with stress-induced changes in gene expression. These findings suggest that the combination of gene expression and protein-DNA interaction data with artificial neural networks can successfully model biological pathways and capture quantitative dependencies between distant regulators and downstream genes.
Abstract: The study of proteomics reached unexpected levels of
interest, as a direct consequence of its discovered influence over
some complex biological phenomena, such as problematic diseases
like cancer. This paper presents a new technique that allows for an
accurate analysis of the human interactome network. It is basically
a two-step analysis process that involves, at first, the detection of
each protein-s absolute importance through the betweenness centrality
computation. Then, the second step determines the functionallyrelated
communities of proteins. For this purpose, we use a community
detection technique that is based on the edge betweenness
calculation. The new technique was thoroughly tested on real biological
data and the results prove some interesting properties of those proteins that are involved in the carcinogenesis process. Apart from its
experimental usefulness, the novel technique is also computationally
effective in terms of execution times. Based on the analysis- results, some topological features of cancer mutated proteins are presented
and a possible optimization solution for cancer drugs design is suggested.
Abstract: Formaldehyde is the illegal chemical substance used
for food preservation in fish and vegetable. It can promote
carcinogenesis. Superoxide dismutases are the important
antioxidative enzymes that catalyze the dismutation of superoxide
anion into oxygen and hydrogen peroxide. The resultant level of
oxidative stress in formaldehyde-treated lymphocytes was
investigated. The formaldehyde concentrations of 0, 20, 40, 60, 80
and 120μmol/L were treated in human lymphocytes for 12 hours.
After 12 treated hours, the superoxide dismutase activity change was
measured in formaldehyde-treated lymphocytes. The results showed
that the formaldehyde concentrations of 60, 80 and 120μmol/L
significantly decreased superoxide dismutase activities in
lymphocytes (P < 0.05). The change of superoxide dismutase
activity in formaldehyde-treated lymphocytes may be the biomarker
for detect cellular injury, such as damage to DNA, due to
formaldehyde exposure.
Abstract: Ultrasound is useful in demonstrating bone mineral
density of regenerating osseous tissue as well as structural alterations.
A proposed ultrasound method, which included ultrasonography and
acoustic parameters measurement, was employed to evaluate its
efficacy in monitoring the bone callus changes in a rabbit tibial
distraction osteogenesis (DO) model.
The findings demonstrated that ultrasonographic images depicted
characteristic changes of the bone callus, typical of histology findings,
during the distraction phase. Follow-up acoustic parameters
measurement of the bone callus, including speed of sound, reflection
and attenuation, showed significant linear changes over time during
the distraction phase. The acoustic parameters obtained during the
distraction phase also showed moderate to strong correlation with
consolidated bone callus density and micro-architecture measured by
micro-computed tomography at the end of the consolidation phase.
The results support the preferred use of ultrasound imaging in the
early monitoring of bone callus changes during DO treatment.
Abstract: MicroRNAs are an important class of gene expression
regulators that are involved in many biological processes including
embryogenesis. miR-125b is a conserved microRNA that is enriched
in the nervous system. We have previously reported the function of
miR-125b in neuronal differentiation of human cell lines. We also
discovered the function of miR-125b in regulating p53 in human and
zebrafish. Here we further characterize the brain defects in zebrafish
embryos injected with morpholinos against miR-125b. Our data
confirm the essential role of miR-125b in brain morphogenesis
particularly in maintaining the balance between proliferation, cell
death and differentiation. We identified lunatic fringe (lfng) as an
additional target of miR-125b in human and zebrafish and suggest
that lfng may mediate the function of miR-125b in neurogenesis.
Together, this report reveals new insights into the function of miR-
125b during neural development of zebrafish.
Abstract: Radiolabeled cyclic RGD peptides targeting integrin αvβ3 are reported as promising agents for the early diagnosis of metastatic tumors. With an aim to improve tumor uptake and retention of the peptide, cyclic RGD peptide dimer E[c (RGDfK)] 2 (E = Glutamic acid, f = phenyl alanine, K = lysine) coupled to the bifunctional chelator DOTA was custom synthesized and radiolabelled with 68Ga. Radiolabelling of cyclic RGD peptide dimer with 68Ga was carried out using HEPES buffer and biological evaluation of the complex was done in nude mice bearing HT29 tumors.
Abstract: Biclustering aims at identifying several biclusters that
reveal potential local patterns from a microarray matrix. A bicluster is
a sub-matrix of the microarray consisting of only a subset of genes
co-regulates in a subset of conditions. In this study, we extend the
motif of subspace clustering to present a K-biclusters clustering (KBC)
algorithm for the microarray biclustering issue. Besides minimizing
the dissimilarities between genes and bicluster centers within all
biclusters, the objective function of the KBC algorithm additionally
takes into account how to minimize the residues within all biclusters
based on the mean square residue model. In addition, the objective
function also maximizes the entropy of conditions to stimulate more
conditions to contribute the identification of biclusters. The KBC
algorithm adopts the K-means type clustering process to efficiently
make the partition of K biclusters be optimized. A set of experiments
on a practical microarray dataset are demonstrated to show the
performance of the proposed KBC algorithm.
Abstract: Many digital signal processing, techniques have been used to automatically distinguish protein coding regions (exons) from non-coding regions (introns) in DNA sequences. In this work, we have characterized these sequences according to their nonlinear dynamical features such as moment invariants, correlation dimension, and largest Lyapunov exponent estimates. We have applied our model to a number of real sequences encoded into a time series using EIIP sequence indicators. In order to discriminate between coding and non coding DNA regions, the phase space trajectory was first reconstructed for coding and non-coding regions. Nonlinear dynamical features are extracted from those regions and used to investigate a difference between them. Our results indicate that the nonlinear dynamical characteristics have yielded significant differences between coding (CR) and non-coding regions (NCR) in DNA sequences. Finally, the classifier is tested on real genes where coding and non-coding regions are well known.
Abstract: Dexamethasone (Dex) is a synthetic glucocorticoid
that is used in therapy. However prolonged treatments with high
doses are often required. This causes side effects that interfere with
the activity of several endocrine systems, including the gonadotropic
axis.
The aim of our study is to determine the effect of Dex on testicular
function in prepubertal Wistar rats.
Newborn Wistar rats are submitted to intraperitoneal injection of
Dex (1μg of Dex dissolved in NaCl 0.9% / 5g bw) for 20 days and
then sacrificed at the age of 40days. A control group received NaCl
0.9%. The rat is weighed daily. The plasmatic levels of testosterone,
LH and FSH were measured by radioimmunoassay. A histomorphometric
study was performed on sections of testis.
Treated groups showed a significant decrease in body weight (p
Abstract: The aim of this study was to estimate the frequency of
EBV infection in Hodgkin's lymphoma (HL) and non-Hodgkin's
lymphoma (NHL) occurring in Jordanian patients. A total of 55
patients with lymphoma were examined in this study. Of 55 patients,
30 and 25 were diagnosed as HL and NHL, respectively. The four
HL subtypes were observed with the majority of the cases exhibited
the mixed cellularity (MC) subtype followed by the nodular sclerosis
(NS). The high grade was found to be the commonest subtype of
NHL in our sample, followed by the low grade. The presence of EBV
virus was detected by immunostating for expression of latent
membrane protein-1 (LMP-1). The frequency of LMP-1 expression
occurred more frequent in patients with HL (60.0%) than in patients
with NHL (32.0%). The frequency of LMP-1 expression was also
higher in patients with MC subtype (61.11%) than those patients with
NS (28.57%). No age or gender difference in occurrence of EBV
infection was observed among patient with HL. By contrast, the
prevalence of EBV infection in NHL patients aged below 50 was
lower (16.66%) than in NHL patients aged 50 or above (46.15%). In
addition, EBV infection was more frequent in females with NHL
(38.46%) than in male with NHL (25%). In NHL cases, the
frequency of EBV infection in intermediate grade (60.0%) was high
when compared with frequency of low (25%) or high grades (25%).
In conclusion, analysis of LMP-1 expression indicates an important
role for this viral oncogene in the pathogenesis of EBV-associated
malignant lymphomas. These data also support the previous findings
that people with EBV may develop lymphoma and that efforts to
maintain low lymphoma should be considered for people with EBV
infection.
Abstract: A gene network gives the knowledge of the regulatory
relationships among the genes. Each gene has its activators and
inhibitors that regulate its expression positively and negatively
respectively. Genes themselves are believed to act as activators and
inhibitors of other genes. They can even activate one set of genes and
inhibit another set. Identifying gene networks is one of the most
crucial and challenging problems in Bioinformatics. Most work done
so far either assumes that there is no time delay in gene regulation or
there is a constant time delay. We here propose a Dynamic Time-
Lagged Correlation Based Method (DTCBM) to learn the gene
networks, which uses time-lagged correlation to find the potential
gene interactions, and then uses a post-processing stage to remove
false gene interactions to common parents, and finally uses dynamic
correlation thresholds for each gene to construct the gene network.
DTCBM finds correlation between gene expression signals shifted in
time, and therefore takes into consideration the multi time delay
relationships among the genes. The implementation of our method is
done in MATLAB and experimental results on Saccharomyces
cerevisiae gene expression data and comparison with other methods
indicate that it has a better performance.
Abstract: A number of competing methodologies have been developed
to identify genes and classify DNA sequences into coding
and non-coding sequences. This classification process is fundamental
in gene finding and gene annotation tools and is one of the most
challenging tasks in bioinformatics and computational biology. An
information theory measure based on mutual information has shown
good accuracy in classifying DNA sequences into coding and noncoding.
In this paper we describe a species independent iterative
approach that distinguishes coding from non-coding sequences using
the mutual information measure (MIM). A set of sixty prokaryotes is
used to extract universal training data. To facilitate comparisons with
the published results of other researchers, a test set of 51 bacterial
and archaeal genomes was used to evaluate MIM. These results
demonstrate that MIM produces superior results while remaining
species independent.
Abstract: The phylogenetic analysis using the most conservative
portions of 18S rRNA gene revealed the phylogenetic relationship
among the two populations where DNA divergence showed that the
nucleotides diversity value were -0.00838 for the Tanjung Dawai,
Kedah and -0.00708 for the Cherating, Pahang populations
respectively. The net nucleotide divergence among populations (Da)
was -0.0073 indicating a low polymorphism among the populations
studied. Total number of mutations in the Tanjung Dawai, Kedah
samples was higher than Cherating, Pahang samples, which are 73 and
59 respectively while shared mutations across the populations were 8,
and reveal the evolutionary in the genome of Malaysian T. gigas. The
tree topology of both populations inferred using Neigbour-joining
method by comparing 1791 bp of partial 18S rRNA sequence revealed
that T. gigas haplotypes were clustered into seven clades, suggesting
that they are genetically diverse among populations which derived
from a common ancestor.
Abstract: Rainbow trout homogametic males, (XX or YY sex genotype), can be obtained, respectively, through masculinisation of genetic females or induced androgenesis. Aim of this study was to compare reproductive potential of neo-males (XX) and super-males (YY) with heterogametic males (XY). We measured spermatozoa motility parameters, sperm concentration, osmolality and characterized protein profiles in samples of stripped and testicular sperm obtained from XY and YY males, and testicular sperm of XX males. The motile spermatozoa, as measured by both subjective method and CASA, showed no differences between testicular sperm of XX males and stripped sperm of XY and YY males whereas testicular sperm of XY and YY males had significantly lower sperm motility. Result of protein densitometry showed similarities in protein profile between seminal plasma of XY and YY males and testicular fluids of XX males. Testis of XX males showed specific histological structures of cysts consists hypertrophied Sertoli cells.
Abstract: The minimal condition for symmetry breaking in morphogenesis of cellular population was investigated using cellular automata based on reaction-diffusion dynamics. In particular, the study looked for the possibility of the emergence of branching structures due to mechanical interactions. The model used two types of cells an external gradient. The results showed that the external gradient influenced movement of cell type-I, also revealed that clusters formed by cells type-II worked as barrier to movement of cells type-I.
Abstract: Using Dynamic Bayesian Networks (DBN) to model genetic regulatory networks from gene expression data is one of the major paradigms for inferring the interactions among genes. Averaging a collection of models for predicting network is desired, rather than relying on a single high scoring model. In this paper, two kinds of model searching approaches are compared, which are Greedy hill-climbing Search with Restarts (GSR) and Markov Chain Monte Carlo (MCMC) methods. The GSR is preferred in many papers, but there is no such comparison study about which one is better for DBN models. Different types of experiments have been carried out to try to give a benchmark test to these approaches. Our experimental results demonstrated that on average the MCMC methods outperform the GSR in accuracy of predicted network, and having the comparable performance in time efficiency. By proposing the different variations of MCMC and employing simulated annealing strategy, the MCMC methods become more efficient and stable. Apart from comparisons between these approaches, another objective of this study is to investigate the feasibility of using DBN modeling approaches for inferring gene networks from few snapshots of high dimensional gene profiles. Through synthetic data experiments as well as systematic data experiments, the experimental results revealed how the performances of these approaches can be influenced as the target gene network varies in the network size, data size, as well as system complexity.
Abstract: Microarray data profiles gene expression on a whole
genome scale, therefore, it provides a good way to study associations
between gene expression and occurrence or progression of cancer.
More and more researchers realized that microarray data is helpful
to predict cancer sample. However, the high dimension of gene
expressions is much larger than the sample size, which makes this
task very difficult. Therefore, how to identify the significant genes
causing cancer becomes emergency and also a hot and hard research
topic. Many feature selection algorithms have been proposed in
the past focusing on improving cancer predictive accuracy at the
expense of ignoring the correlations between the features. In this
work, a novel framework (named by SGS) is presented for stable gene
selection and efficient cancer prediction . The proposed framework
first performs clustering algorithm to find the gene groups where
genes in each group have higher correlation coefficient, and then
selects the significant genes in each group with Bayesian Lasso and
important gene groups with group Lasso, and finally builds prediction
model based on the shrinkage gene space with efficient classification
algorithm (such as, SVM, 1NN, Regression and etc.). Experiment
results on real world data show that the proposed framework often
outperforms the existing feature selection and prediction methods,
say SAM, IG and Lasso-type prediction model.