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A review on the computational approaches for gene regulatory network construction

Chai LE, Loh SK, Low ST, Mohamad MS, Deris S, Zakaria Z

Comput Biol Med, 2014 May;48:55-65.
PMID: 24637147 DOI: 10.1016/j.compbiomed.2014.02.011

Many biological research areas such as drug design require gene regulatory networks to provide clear insight and understanding of the cellular process in living cells. This is because interactions among the genes and their products play an important role in many molecular processes. A gene regulatory network can act as a blueprint for the researchers to observe the relationships among genes. Due to its importance, several computational approaches have been proposed to infer gene regulatory networks from gene expression data. In this review, six inference approaches are discussed: Boolean network, probabilistic Boolean network, ordinary differential equation, neural network, Bayesian network, and dynamic Bayesian network. These approaches are discussed in terms of introduction, methodology and recent applications of these approaches in gene regulatory network construction. These approaches are also compared in the discussion section. Furthermore, the strengths and weaknesses of these computational approaches are described.
A hybrid of ant colony optimization and minimization of metabolic adjustment to improve the production of succinic acid in Escherichia coli

Chong SK, Mohamad MS, Mohamed Salleh AH, Choon YW, Chong CK, Deris S

Comput Biol Med, 2014 Jun;49:74-82.
PMID: 24763079 DOI: 10.1016/j.compbiomed.2014.03.011

This paper presents a study on gene knockout strategies to identify candidate genes to be knocked out for improving the production of succinic acid in Escherichia coli. Succinic acid is widely used as a precursor for many chemicals, for example production of antibiotics, therapeutic proteins and food. However, the chemical syntheses of succinic acid using the traditional methods usually result in the production that is far below their theoretical maximums. In silico gene knockout strategies are commonly implemented to delete the gene in E. coli to overcome this problem. In this paper, a hybrid of Ant Colony Optimization (ACO) and Minimization of Metabolic Adjustment (MoMA) is proposed to identify gene knockout strategies to improve the production of succinic acid in E. coli. As a result, the hybrid algorithm generated a list of knockout genes, succinic acid production rate and growth rate for E. coli after gene knockout. The results of the hybrid algorithm were compared with the previous methods, OptKnock and MOMAKnock. It was found that the hybrid algorithm performed better than OptKnock and MOMAKnock in terms of the production rate. The information from the results produced from the hybrid algorithm can be used in wet laboratory experiments to increase the production of succinic acid in E. coli.
Breast cancer detection from MR images through an auto-probing discrete Fourier transform system

Sim KS, Chia FK, Nia ME, Tso CP, Chong AK, Abbas SF, et al.

Comput Biol Med, 2014 Jun;49:46-59.
PMID: 24736203 DOI: 10.1016/j.compbiomed.2014.03.003

A computer-aided detection auto-probing (CADAP) system is presented for detecting breast lesions using dynamic contrast enhanced magnetic resonance imaging, through a spatial-based discrete Fourier transform. The stand-alone CADAP system reduces noise, refines region of interest (ROI) automatically, and detects the breast lesion with minimal false positive detection. The lesions are then classified and colourised according to their characteristics, whether benign, suspicious or malignant. To enhance the visualisation, the entire analysed ROI is constructed into a 3-D image, so that the user can diagnose based on multiple views on the ROI. The proposed method has been applied to 101 sets of digital images, and the results compared with the biopsy results done by radiologists. The proposed scheme is able to identify breast cancer regions accurately and efficiently.
Automated diagnosis of Age-related Macular Degeneration using greyscale features from digital fundus images

Mookiah MR, Acharya UR, Koh JE, Chandran V, Chua CK, Tan JH, et al.

Comput Biol Med, 2014 Oct;53:55-64.
PMID: 25127409 DOI: 10.1016/j.compbiomed.2014.07.015

Age-related Macular Degeneration (AMD) is one of the major causes of vision loss and blindness in ageing population. Currently, there is no cure for AMD, however early detection and subsequent treatment may prevent the severe vision loss or slow the progression of the disease. AMD can be classified into two types: dry and wet AMDs. The people with macular degeneration are mostly affected by dry AMD. Early symptoms of AMD are formation of drusen and yellow pigmentation. These lesions are identified by manual inspection of fundus images by the ophthalmologists. It is a time consuming, tiresome process, and hence an automated diagnosis of AMD screening tool can aid clinicians in their diagnosis significantly. This study proposes an automated dry AMD detection system using various entropies (Shannon, Kapur, Renyi and Yager), Higher Order Spectra (HOS) bispectra features, Fractional Dimension (FD), and Gabor wavelet features extracted from greyscale fundus images. The features are ranked using t-test, Kullback-Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance (CBBD), Receiver Operating Characteristics (ROC) curve-based and Wilcoxon ranking methods in order to select optimum features and classified into normal and AMD classes using Naive Bayes (NB), k-Nearest Neighbour (k-NN), Probabilistic Neural Network (PNN), Decision Tree (DT) and Support Vector Machine (SVM) classifiers. The performance of the proposed system is evaluated using private (Kasturba Medical Hospital, Manipal, India), Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) datasets. The proposed system yielded the highest average classification accuracies of 90.19%, 95.07% and 95% with 42, 54 and 38 optimal ranked features using SVM classifier for private, ARIA and STARE datasets respectively. This automated AMD detection system can be used for mass fundus image screening and aid clinicians by making better use of their expertise on selected images that require further examination.
Computerized segmentation and measurement of chronic wound images

Ahmad Fauzi MF, Khansa I, Catignani K, Gordillo G, Sen CK, Gurcan MN

Comput Biol Med, 2015 May;60:74-85.
PMID: 25756704 DOI: 10.1016/j.compbiomed.2015.02.015

An estimated 6.5 million patients in the United States are affected by chronic wounds, with more than US$25 billion and countless hours spent annually for all aspects of chronic wound care. There is a need for an intelligent software tool to analyze wound images, characterize wound tissue composition, measure wound size, and monitor changes in wound in between visits. Performed manually, this process is very time-consuming and subject to intra- and inter-reader variability. In this work, our objective is to develop methods to segment, measure and characterize clinically presented chronic wounds from photographic images. The first step of our method is to generate a Red-Yellow-Black-White (RYKW) probability map, which then guides the segmentation process using either optimal thresholding or region growing. The red, yellow and black probability maps are designed to handle the granulation, slough and eschar tissues, respectively; while the white probability map is to detect the white label card for measurement calibration purposes. The innovative aspects of this work include defining a four-dimensional probability map specific to wound characteristics, a computationally efficient method to segment wound images utilizing the probability map, and auto-calibration of wound measurements using the content of the image. These methods were applied to 80 wound images, captured in a clinical setting at the Ohio State University Comprehensive Wound Center, with the ground truth independently generated by the consensus of at least two clinicians. While the mean inter-reader agreement between the readers varied between 67.4% and 84.3%, the computer achieved an average accuracy of 75.1%.
Computer-aided diagnosis of Myocardial Infarction using ultrasound images with DWT, GLCM and HOS methods: A comparative study

Vidya KS, Ng EY, Acharya UR, Chou SM, Tan RS, Ghista DN

Comput Biol Med, 2015 Jul;62:86-93.
PMID: 25912990 DOI: 10.1016/j.compbiomed.2015.03.033

Myocardial Infarction (MI) or acute MI (AMI) is one of the leading causes of death worldwide. Precise and timely identification of MI and extent of muscle damage helps in early treatment and reduction in the time taken for further tests. MI diagnosis using 2D echocardiography is prone to inter-/intra-observer variability in the assessment. Therefore, a computerised scheme based on image processing and artificial intelligent techniques can reduce the workload of clinicians and improve the diagnosis accuracy. A Computer-Aided Diagnosis (CAD) of infarcted and normal ultrasound images will be useful for clinicians. In this study, the performance of CAD approach using Discrete Wavelet Transform (DWT), second order statistics calculated from Gray-Level Co-Occurrence Matrix (GLCM) and Higher-Order Spectra (HOS) texture descriptors are compared. The proposed system is validated using 400 MI and 400 normal ultrasound images, obtained from 80 patients with MI and 80 normal subjects. The extracted features are ranked based on t-value and fed to the Support Vector Machine (SVM) classifier to obtain the best performance using minimum number of features. The features extracted from DWT coefficients obtained an accuracy of 99.5%, sensitivity of 99.75% and specificity of 99.25%; GLCM have achieved an accuracy of 85.75%, sensitivity of 90.25% and specificity of 81.25%; and HOS obtained an accuracy of 93.0%, sensitivity of 94.75% and specificity of 91.25%. Among the three techniques presented DWT yielded the highest classification accuracy. Thus, the proposed CAD approach may be used as a complementary tool to assist cardiologists in making a more accurate diagnosis for the presence of MI.
Local configuration pattern features for age-related macular degeneration characterization and classification

Mookiah MR, Acharya UR, Fujita H, Koh JE, Tan JH, Noronha K, et al.

Comput Biol Med, 2015 Aug;63:208-18.
PMID: 26093788 DOI: 10.1016/j.compbiomed.2015.05.019

Age-related Macular Degeneration (AMD) is an irreversible and chronic medical condition characterized by drusen, Choroidal Neovascularization (CNV) and Geographic Atrophy (GA). AMD is one of the major causes of visual loss among elderly people. It is caused by the degeneration of cells in the macula which is responsible for central vision. AMD can be dry or wet type, however dry AMD is most common. It is classified into early, intermediate and late AMD. The early detection and treatment may help one to stop the progression of the disease. Automated AMD diagnosis may reduce the screening time of the clinicians. In this work, we have introduced LCP to characterize normal and AMD classes using fundus images. Linear Configuration Coefficients (CC) and Pattern Occurrence (PO) features are extracted from fundus images. These extracted features are ranked using p-value of the t-test and fed to various supervised classifiers viz. Decision Tree (DT), Nearest Neighbour (k-NN), Naive Bayes (NB), Probabilistic Neural Network (PNN) and Support Vector Machine (SVM) to classify normal and AMD classes. The performance of the system is evaluated using both private (Kasturba Medical Hospital, Manipal, India) and public domain datasets viz. Automated Retinal Image Analysis (ARIA) and STructured Analysis of the Retina (STARE) using ten-fold cross validation. The proposed approach yielded best performance with a highest average accuracy of 97.78%, sensitivity of 98.00% and specificity of 97.50% for STARE dataset using 22 significant features. Hence, this system can be used as an aiding tool to the clinicians during mass eye screening programs to diagnose AMD.
Application of different imaging modalities for diagnosis of Diabetic Macular Edema: A review

Mookiah MR, Acharya UR, Fujita H, Tan JH, Chua CK, Bhandary SV, et al.

Comput Biol Med, 2015 Nov 1;66:295-315.
PMID: 26453760 DOI: 10.1016/j.compbiomed.2015.09.012

Diabetic Macular Edema (DME) is caused by accumulation of extracellular fluid from hyperpermeable capillaries within the macula. DME is one of the leading causes of blindness among Diabetes Mellitus (DM) patients. Early detection followed by laser photocoagulation can save the visual loss. This review discusses various imaging modalities viz. biomicroscopy, Fluorescein Angiography (FA), Optical Coherence Tomography (OCT) and colour fundus photographs used for diagnosis of DME. Various automated DME grading systems using retinal fundus images, associated retinal image processing techniques for fovea, exudate detection and segmentation are presented. We have also compared various imaging modalities and automated screening methods used for DME grading. The reviewed literature indicates that FA and OCT identify DME related changes accurately. FA is an invasive method, which uses fluorescein dye, and OCT is an expensive imaging method compared to fundus photographs. Moreover, using fundus images DME can be identified and automated. DME grading algorithms can be implemented for telescreening. Hence, fundus imaging based DME grading is more suitable and affordable method compared to biomicroscopy, FA, and OCT modalities.
Prediction of recombinant protein overexpression in Escherichia coli using a machine learning based model (RPOLP)

Habibi N, Norouzi A, Mohd Hashim SZ, Shamsir MS, Samian R

Comput Biol Med, 2015 Nov 1;66:330-6.
PMID: 26476414 DOI: 10.1016/j.compbiomed.2015.09.015

Recombinant protein overexpression, an important biotechnological process, is ruled by complex biological rules which are mostly unknown, is in need of an intelligent algorithm so as to avoid resource-intensive lab-based trial and error experiments in order to determine the expression level of the recombinant protein. The purpose of this study is to propose a predictive model to estimate the level of recombinant protein overexpression for the first time in the literature using a machine learning approach based on the sequence, expression vector, and expression host. The expression host was confined to Escherichia coli which is the most popular bacterial host to overexpress recombinant proteins. To provide a handle to the problem, the overexpression level was categorized as low, medium and high. A set of features which were likely to affect the overexpression level was generated based on the known facts (e.g. gene length) and knowledge gathered from related literature. Then, a representative sub-set of features generated in the previous objective was determined using feature selection techniques. Finally a predictive model was developed using random forest classifier which was able to adequately classify the multi-class imbalanced small dataset constructed. The result showed that the predictive model provided a promising accuracy of 80% on average, in estimating the overexpression level of a recombinant protein.
Regularized logistic regression with adjusted adaptive elastic net for gene selection in high dimensional cancer classification

Algamal ZY, Lee MH

Comput Biol Med, 2015 Dec 1;67:136-45.
PMID: 26520484 DOI: 10.1016/j.compbiomed.2015.10.008

Cancer classification and gene selection in high-dimensional data have been popular research topics in genetics and molecular biology. Recently, adaptive regularized logistic regression using the elastic net regularization, which is called the adaptive elastic net, has been successfully applied in high-dimensional cancer classification to tackle both estimating the gene coefficients and performing gene selection simultaneously. The adaptive elastic net originally used elastic net estimates as the initial weight, however, using this weight may not be preferable for certain reasons: First, the elastic net estimator is biased in selecting genes. Second, it does not perform well when the pairwise correlations between variables are not high. Adjusted adaptive regularized logistic regression (AAElastic) is proposed to address these issues and encourage grouping effects simultaneously. The real data results indicate that AAElastic is significantly consistent in selecting genes compared to the other three competitor regularization methods. Additionally, the classification performance of AAElastic is comparable to the adaptive elastic net and better than other regularization methods. Thus, we can conclude that AAElastic is a reliable adaptive regularized logistic regression method in the field of high-dimensional cancer classification.
On fuzzy semantic similarity measure for DNA coding

Ahmad M, Jung LT, Bhuiyan MA

Comput Biol Med, 2016 Feb 1;69:144-51.
PMID: 26773936 DOI: 10.1016/j.compbiomed.2015.12.017

A coding measure scheme numerically translates the DNA sequence to a time domain signal for protein coding regions identification. A number of coding measure schemes based on numerology, geometry, fixed mapping, statistical characteristics and chemical attributes of nucleotides have been proposed in recent decades. Such coding measure schemes lack the biologically meaningful aspects of nucleotide data and hence do not significantly discriminate coding regions from non-coding regions. This paper presents a novel fuzzy semantic similarity measure (FSSM) coding scheme centering on FSSM codons׳ clustering and genetic code context of nucleotides. Certain natural characteristics of nucleotides i.e. appearance as a unique combination of triplets, preserving special structure and occurrence, and ability to own and share density distributions in codons have been exploited in FSSM. The nucleotides׳ fuzzy behaviors, semantic similarities and defuzzification based on the center of gravity of nucleotides revealed a strong correlation between nucleotides in codons. The proposed FSSM coding scheme attains a significant enhancement in coding regions identification i.e. 36-133% as compared to other existing coding measure schemes tested over more than 250 benchmarked and randomly taken DNA datasets of different organisms.
Application of wavelet techniques for cancer diagnosis using ultrasound images: A Review

Sudarshan VK, Mookiah MR, Acharya UR, Chandran V, Molinari F, Fujita H, et al.

Comput Biol Med, 2016 Feb 1;69:97-111.
PMID: 26761591 DOI: 10.1016/j.compbiomed.2015.12.006

Ultrasound is an important and low cost imaging modality used to study the internal organs of human body and blood flow through blood vessels. It uses high frequency sound waves to acquire images of internal organs. It is used to screen normal, benign and malignant tissues of various organs. Healthy and malignant tissues generate different echoes for ultrasound. Hence, it provides useful information about the potential tumor tissues that can be analyzed for diagnostic purposes before therapeutic procedures. Ultrasound images are affected with speckle noise due to an air gap between the transducer probe and the body. The challenge is to design and develop robust image preprocessing, segmentation and feature extraction algorithms to locate the tumor region and to extract subtle information from isolated tumor region for diagnosis. This information can be revealed using a scale space technique such as the Discrete Wavelet Transform (DWT). It decomposes an image into images at different scales using low pass and high pass filters. These filters help to identify the detail or sudden changes in intensity in the image. These changes are reflected in the wavelet coefficients. Various texture, statistical and image based features can be extracted from these coefficients. The extracted features are subjected to statistical analysis to identify the significant features to discriminate normal and malignant ultrasound images using supervised classifiers. This paper presents a review of wavelet techniques used for preprocessing, segmentation and feature extraction of breast, thyroid, ovarian and prostate cancer using ultrasound images.
An integrated index for automated detection of infarcted myocardium from cross-sectional echocardiograms using texton-based features (Part 1)

Sudarshan VK, Acharya UR, Ng EY, Tan RS, Chou SM, Ghista DN

Comput Biol Med, 2016 Apr 1;71:231-40.
PMID: 26898671 DOI: 10.1016/j.compbiomed.2016.01.028

Cross-sectional view echocardiography is an efficient non-invasive diagnostic tool for characterizing Myocardial Infarction (MI) and stages of expansion leading to heart failure. An automated computer-aided technique of cross-sectional echocardiography feature assessment can aid clinicians in early and more reliable detection of MI patients before subsequent catastrophic post-MI medical conditions. Therefore, this paper proposes a novel Myocardial Infarction Index (MII) to discriminate infarcted and normal myocardium using features extracted from apical cross-sectional views of echocardiograms. The cross-sectional view of normal and MI echocardiography images are represented as textons using Maximum Responses (MR8) filter banks. Fractal Dimension (FD), Higher-Order Statistics (HOS), Hu's moments, Gabor Transform features, Fuzzy Entropy (FEnt), Energy, Local binary Pattern (LBP), Renyi's Entropy (REnt), Shannon's Entropy (ShEnt), and Kapur's Entropy (KEnt) features are extracted from textons. These features are ranked using t-test and fuzzy Max-Relevancy and Min-Redundancy (mRMR) ranking methods. Then, combinations of highly ranked features are used in the formulation and development of an integrated MII. This calculated novel MII is used to accurately and quickly detect infarcted myocardium by using one numerical value. Also, the highly ranked features are subjected to classification using different classifiers for the characterization of normal and MI LV ultrasound images using a minimum number of features. Our current technique is able to characterize MI with an average accuracy of 94.37%, sensitivity of 91.25% and specificity of 97.50% with 8 apical four chambers view features extracted from only single frame per patient making this a more reliable and accurate classification.
Data mining framework for identification of myocardial infarction stages in ultrasound: A hybrid feature extraction paradigm (PART 2)

Sudarshan VK, Acharya UR, Ng EY, Tan RS, Chou SM, Ghista DN

Comput Biol Med, 2016 Apr 1;71:241-51.
PMID: 26897481 DOI: 10.1016/j.compbiomed.2016.01.029

Early expansion of infarcted zone after Acute Myocardial Infarction (AMI) has serious short and long-term consequences and contributes to increased mortality. Thus, identification of moderate and severe phases of AMI before leading to other catastrophic post-MI medical condition is most important for aggressive treatment and management. Advanced image processing techniques together with robust classifier using two-dimensional (2D) echocardiograms may aid for automated classification of the extent of infarcted myocardium. Therefore, this paper proposes novel algorithms namely Curvelet Transform (CT) and Local Configuration Pattern (LCP) for an automated detection of normal, moderately infarcted and severely infarcted myocardium using 2D echocardiograms. The methodology extracts the LCP features from CT coefficients of echocardiograms. The obtained features are subjected to Marginal Fisher Analysis (MFA) dimensionality reduction technique followed by fuzzy entropy based ranking method. Different classifiers are used to differentiate ranked features into three classes normal, moderate and severely infarcted based on the extent of damage to myocardium. The developed algorithm has achieved an accuracy of 98.99%, sensitivity of 98.48% and specificity of 100% for Support Vector Machine (SVM) classifier using only six features. Furthermore, we have developed an integrated index called Myocardial Infarction Risk Index (MIRI) to detect the normal, moderately and severely infarcted myocardium using a single number. The proposed system may aid the clinicians in faster identification and quantification of the extent of infarcted myocardium using 2D echocardiogram. This system may also aid in identifying the person at risk of developing heart failure based on the extent of infarcted myocardium.
Novel risk index for the identification of age-related macular degeneration using radon transform and DWT features

Acharya UR, Mookiah MR, Koh JE, Tan JH, Noronha K, Bhandary SV, et al.

Comput Biol Med, 2016 06 01;73:131-40.
PMID: 27107676 DOI: 10.1016/j.compbiomed.2016.04.009

Age-related Macular Degeneration (AMD) affects the central vision of aged people. It can be diagnosed due to the presence of drusen, Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in the fundus images. It is labor intensive and time-consuming for the ophthalmologists to screen these images. An automated digital fundus photography based screening system can overcome these drawbacks. Such a safe, non-contact and cost-effective platform can be used as a screening system for dry AMD. In this paper, we are proposing a novel algorithm using Radon Transform (RT), Discrete Wavelet Transform (DWT) coupled with Locality Sensitive Discriminant Analysis (LSDA) for automated diagnosis of AMD. First the image is subjected to RT followed by DWT. The extracted features are subjected to dimension reduction using LSDA and ranked using t-test. The performance of various supervised classifiers namely Decision Tree (DT), Support Vector Machine (SVM), Probabilistic Neural Network (PNN) and k-Nearest Neighbor (k-NN) are compared to automatically discriminate to normal and AMD classes using ranked LSDA components. The proposed approach is evaluated using private and public datasets such as ARIA and STARE. The highest classification accuracy of 99.49%, 96.89% and 100% are reported for private, ARIA and STARE datasets. Also, AMD index is devised using two LSDA components to distinguish two classes accurately. Hence, this proposed system can be extended for mass AMD screening.
Automated screening system for retinal health using bi-dimensional empirical mode decomposition and integrated index

Acharya UR, Mookiah MR, Koh JE, Tan JH, Bhandary SV, Rao AK, et al.

Comput Biol Med, 2016 08 01;75:54-62.
PMID: 27253617 DOI: 10.1016/j.compbiomed.2016.04.015

Posterior Segment Eye Diseases (PSED) namely Diabetic Retinopathy (DR), glaucoma and Age-related Macular Degeneration (AMD) are the prime causes of vision loss globally. Vision loss can be prevented, if these diseases are detected at an early stage. Structural abnormalities such as changes in cup-to-disc ratio, Hard Exudates (HE), drusen, Microaneurysms (MA), Cotton Wool Spots (CWS), Haemorrhages (HA), Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in PSED can be identified by manual examination of fundus images by clinicians. However, manual screening is labour-intensive, tiresome and time consuming. Hence, there is a need to automate the eye screening. In this work Bi-dimensional Empirical Mode Decomposition (BEMD) technique is used to decompose fundus images into 2D Intrinsic Mode Functions (IMFs) to capture variations in the pixels due to morphological changes. Further, various entropy namely Renyi, Fuzzy, Shannon, Vajda, Kapur and Yager and energy features are extracted from IMFs. These extracted features are ranked using Chernoff Bound and Bhattacharyya Distance (CBBD), Kullback-Leibler Divergence (KLD), Fuzzy-minimum Redundancy Maximum Relevance (FmRMR), Wilcoxon, Receiver Operating Characteristics Curve (ROC) and t-test methods. Further, these ranked features are fed to Support Vector Machine (SVM) classifier to classify normal and abnormal (DR, AMD and glaucoma) classes. The performance of the proposed eye screening system is evaluated using 800 (Normal=400 and Abnormal=400) digital fundus images and 10-fold cross validation method. Our proposed system automatically identifies normal and abnormal classes with an average accuracy of 88.63%, sensitivity of 86.25% and specificity of 91% using 17 optimal features ranked using CBBD and SVM-Radial Basis Function (RBF) classifier. Moreover, a novel Retinal Risk Index (RRI) is developed using two significant features to distinguish two classes using single number. Such a system helps to reduce eye screening time in polyclinics or community-based mass screening. They will refer the patients to main hospitals only if the diagnosis belong to the abnormal class. Hence, the main hospitals will not be unnecessarily crowded and doctors can devote their time for other urgent cases.
Identification of informative genes and pathways using an improved penalized support vector machine with a weighting scheme

Chan WH, Mohamad MS, Deris S, Zaki N, Kasim S, Omatu S, et al.

Comput Biol Med, 2016 10 01;77:102-15.
PMID: 27522238 DOI: 10.1016/j.compbiomed.2016.08.004

Incorporation of pathway knowledge into microarray analysis has brought better biological interpretation of the analysis outcome. However, most pathway data are manually curated without specific biological context. Non-informative genes could be included when the pathway data is used for analysis of context specific data like cancer microarray data. Therefore, efficient identification of informative genes is inevitable. Embedded methods like penalized classifiers have been used for microarray analysis due to their embedded gene selection. This paper proposes an improved penalized support vector machine with absolute t-test weighting scheme to identify informative genes and pathways. Experiments are done on four microarray data sets. The results are compared with previous methods using 10-fold cross validation in terms of accuracy, sensitivity, specificity and F-score. Our method shows consistent improvement over the previous methods and biological validation has been done to elucidate the relation of the selected genes and pathway with the phenotype under study.
Observer performance in characterization of carotid plaque texture and surface characteristics with 3D versus 2D ultrasound

Leong SS, Vijayananthan A, Yaakup NA, Shah N, Ng KH, Acharya UR, et al.

Comput Biol Med, 2016 11 01;78:58-64.
PMID: 27658262 DOI: 10.1016/j.compbiomed.2016.09.006

OBJECTIVE: To determine the reproducibility of three-dimensional (3D) ultrasound (US) over two-dimensional (2D) US in characterizing atherosclerotic carotid plaques using inter- and intra-observer agreement metrics.
METHODS: A Total of 51 patients with 105 carotid artery plaques were screened using 3D and 2D US probes attached to the same US scanner. Two independent observers characterized the plaques based on the morphological features namely echotexture, echogenicity and surface characteristics. The scores assigned to each morphological feature were used to determine intra- and inter-observer performance. The level of agreement was measured using Kappa coefficient.
RESULTS: The first observer with 2D US showed fair (k=0.4-0.59) and very strong (k>0.8) with 3D US intra-observer agreements using three morphological features. The second observer indicated moderate strong (k=0.6-0.79) with 2D US and very strong with 3D US (k>0.8) intra-observer performances. Moderate strong (k=0.6-0.79) and very strong (k>0.8) inter-observer agreements were reported with 2D US and 3D US respectively. The results with 2D and 3D US were correlated 62% using only echotexture and 56% using surface morphology coupled with echogenicity. 3D US gave a lower score than 2D 71% of the time (p=0.005) in disagreement cases.
CONCLUSION: High reproducibility in carotid plaque characterization was obtained using 3D US rather than 2D US. Hence, it can be a preferred imaging modality in routine or follow up plaque screening of patients with carotid artery disease.
Automated characterization of fatty liver disease and cirrhosis using curvelet transform and entropy features extracted from ultrasound images

Acharya UR, Raghavendra U, Fujita H, Hagiwara Y, Koh JE, Jen Hong T, et al.

Comput Biol Med, 2016 12 01;79:250-258.
PMID: 27825038 DOI: 10.1016/j.compbiomed.2016.10.022

Fatty liver disease (FLD) is reversible disease and can be treated, if it is identified at an early stage. However, if diagnosed at the later stage, it can progress to an advanced liver disease such as cirrhosis which may ultimately lead to death. Therefore, it is essential to detect it at an early stage before the disease progresses to an irreversible stage. Several non-invasive computer-aided techniques are proposed to assist in the early detection of FLD and cirrhosis using ultrasound images. In this work, we are proposing an algorithm to discriminate automatically the normal, FLD and cirrhosis ultrasound images using curvelet transform (CT) method. Higher order spectra (HOS) bispectrum, HOS phase, fuzzy, Kapoor, max, Renyi, Shannon, Vajda and Yager entropies are extracted from CT coefficients. These extracted features are subjected to locality sensitive discriminant analysis (LSDA) feature reduction method. Then these LSDA coefficients ranked based on F-value are fed to different classifiers to choose the best performing classifier using minimum number of features. Our proposed technique can characterize normal, FLD and cirrhosis using probabilistic neural network (PNN) classifier with an accuracy of 97.33%, specificity of 100.00% and sensitivity of 96.00% using only six features. In addition, these chosen features are used to develop a liver disease index (LDI) to differentiate the normal, FLD and cirrhosis classes using a single number. This can significantly help the radiologists to discriminate FLD and cirrhosis in their routine liver screening.
Automated diagnosis of congestive heart failure using dual tree complex wavelet transform and statistical features extracted from 2s of ECG signals

Sudarshan VK, Acharya UR, Oh SL, Adam M, Tan JH, Chua CK, et al.

Comput Biol Med, 2017 04 01;83:48-58.
PMID: 28231511 DOI: 10.1016/j.compbiomed.2017.01.019

Identification of alarming features in the electrocardiogram (ECG) signal is extremely significant for the prediction of congestive heart failure (CHF). ECG signal analysis carried out using computer-aided techniques can speed up the diagnosis process and aid in the proper management of CHF patients. Therefore, in this work, dual tree complex wavelets transform (DTCWT)-based methodology is proposed for an automated identification of ECG signals exhibiting CHF from normal. In the experiment, we have performed a DTCWT on ECG segments of 2s duration up to six levels to obtain the coefficients. From these DTCWT coefficients, statistical features are extracted and ranked using Bhattacharyya, entropy, minimum redundancy maximum relevance (mRMR), receiver-operating characteristics (ROC), Wilcoxon, t-test and reliefF methods. Ranked features are subjected to k-nearest neighbor (KNN) and decision tree (DT) classifiers for automated differentiation of CHF and normal ECG signals. We have achieved 99.86% accuracy, 99.78% sensitivity and 99.94% specificity in the identification of CHF affected ECG signals using 45 features. The proposed method is able to detect CHF patients accurately using only 2s of ECG signal length and hence providing sufficient time for the clinicians to further investigate on the severity of CHF and treatments.

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