GenSo-FDSS: a neural-fuzzy decision support system for pediatric ALL cancer subtype identification using gene expression data

OBJECTIVE Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood, representing nearly one third of all pediatric cancers. Currently, the treatment of pediatric ALL is centered on tailoring the intensity of the therapy applied to a patient's risk of relapse, which is linked to the type of leukemia the patient has. Hence, accurate and correct diagnosis of the various leukemia subtypes becomes an important first step in the treatment process. Recently, gene expression profiling using DNA microarrays has been shown to be a viable and accurate diagnostic tool to identify the known prognostically important ALL subtypes. Thus, there is currently a huge interest in developing autonomous classification systems for cancer diagnosis using gene expression data. This is to achieve an unbiased analysis of the data and also partly to handle the large amount of genetic information extracted from the DNA microarrays. METHODOLOGY Generally, existing medical decision support systems (DSS) for cancer classification and diagnosis are based on traditional statistical methods such as Bayesian decision theory and machine learning models such as neural networks (NN) and support vector machine (SVM). Though high accuracies have been reported for these systems, they fall short on certain critical areas. These included (a) being able to present the extracted knowledge and explain the computed solutions to the users; (b) having a logical deduction process that is similar and intuitive to the human reasoning process; and (c) flexible enough to incorporate new knowledge without running the risk of eroding old but valid information. On the other hand, a neural fuzzy system, which is synthesized to emulate the human ability to learn and reason in the presence of imprecise and incomplete information, has the ability to overcome the above-mentioned shortcomings. However, existing neural fuzzy systems have their own limitations when used in the design and implementation of DSS. Hence, this paper proposed the use of a novel neural fuzzy system: the generic self-organising fuzzy neural network (GenSoFNN) with truth-value restriction (TVR) fuzzy inference, as a fuzzy DSS (denoted as GenSo-FDSS) for the classification of ALL subtypes using gene expression data. RESULTS AND CONCLUSION The performance of the GenSo-FDSS system is encouraging when benchmarked against those of NN, SVM and the K-nearest neighbor (K-NN) classifier. On average, a classification rate of above 90% has been achieved using the GenSo-FDSS system.

[1]  Ramon López de Mántaras,et al.  Approximate Reasoning Models , 1990 .

[2]  S. Dudoit,et al.  Comparison of Discrimination Methods for the Classification of Tumors Using Gene Expression Data , 2002 .

[3]  S. Schor STATISTICS: AN INTRODUCTION. , 1965, The Journal of trauma.

[4]  Whye Loon. Tung A generalized framework for fuzzy neural architecture. , 2004 .

[5]  Cornelius T. Leondes Fuzzy systems, neural networks, and expert systems , 2003 .

[6]  Roger E. Kirk,et al.  Statistics: An Introduction , 1998 .

[7]  S. Grossberg,et al.  Adaptive pattern classification and universal recoding: I. Parallel development and coding of neural feature detectors , 1976, Biological Cybernetics.

[8]  Richard S. Sutton,et al.  Introduction to Reinforcement Learning , 1998 .

[9]  Ruowei Zhou,et al.  POPFNN-AAR(S): a pseudo outer-product based fuzzy neural network , 1999, IEEE Trans. Syst. Man Cybern. Part B.

[10]  Chin-Teng Lin,et al.  An On-Line Self-Constructing Neural Fuzzy Inference Network and Its Applications , 1998 .

[11]  Geoffrey E. Hinton,et al.  Learning internal representations by error propagation , 1986 .

[12]  James M. Keller,et al.  Neural network implementation of fuzzy logic , 1992 .

[13]  Hiok Chai Quek,et al.  A novel approach to the derivation of fuzzy membership functions using the Falcon-MART architecture , 2001, Pattern Recognit. Lett..

[14]  Hamid R. Berenji,et al.  Learning and tuning fuzzy logic controllers through reinforcements , 1992, IEEE Trans. Neural Networks.

[15]  Ash A. Alizadeh,et al.  Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling , 2000, Nature.

[16]  Senén Barro,et al.  Reasoning with truth values on compacted fuzzy chained rules , 1998, IEEE Trans. Syst. Man Cybern. Part B.

[17]  Wentian Li,et al.  How Many Genes are Needed for a Discriminant Microarray Data Analysis , 2001, physics/0104029.

[18]  T. Pavlidis,et al.  Fuzzy sets and their applications to cognitive and decision processes , 1977 .

[19]  Chin-Teng Lin,et al.  An online self-constructing neural fuzzy inference network and its applications , 1998, IEEE Trans. Fuzzy Syst..

[20]  Chai Quek,et al.  PACL-FNNS: A Novel Class of Falcon-Like Fuzzy Neural Networks Based on Positive and Negative Exemplars , 2002 .

[21]  H. Carter Fuzzy Sets and Systems — Theory and Applications , 1982 .

[22]  I. Turksen,et al.  An approximate analogical reasoning schema based on similarity measures and interval-valued fuzzy sets , 1990 .

[23]  Liya Ding,et al.  Approximate case-based reasoning on neural networks , 1994, Int. J. Approx. Reason..

[24]  David Elashoff,et al.  Mapping single and multigenetic traits in S. cerevisiae by genomic mismatch scanning and DNA microarrays , 1999, Nature Genetics.

[25]  R. Gelber,et al.  Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. , 2001, Blood.

[26]  Ronald R. Yager,et al.  Modeling and formulating fuzzy knowledge bases using neural networks , 1994, Neural Networks.

[27]  Hiok Chai Quek,et al.  Pseudo-outer product based fuzzy neural network fingerprint verification system , 2001, Neural Networks.

[28]  Hiok Chai Quek,et al.  MCES: A Novel Monte Carlo Evaluative Selection Approach for Objective Feature Selections , 2007, IEEE Transactions on Neural Networks.

[29]  Hiok Chai Quek,et al.  DIC: A Novel Discrete Incremental Clustering Technique for the Derivation of Fuzzy Membership Functions , 2002, PRICAI.

[30]  Hiok Chai Quek,et al.  GenSoFNN: a generic self-organizing fuzzy neural network , 2002, IEEE Trans. Neural Networks.

[31]  George S. Moschytz,et al.  A CNN-based Fingerprint Verification System , 2006 .

[32]  Preston Hunter,et al.  Genome-directed primers for selective labeling of bacterial transcripts for DNA microarray analysis , 2000, Nature Biotechnology.

[33]  Nikola K. Kasabov,et al.  Evolving connectionist systems for knowledge discovery from gene expression data of cancer tissue , 2003, Artif. Intell. Medicine.

[34]  Michel Pasquier,et al.  Fuzzylot: a novel self-organising fuzzy-neural rule-based pilot system for automated vehicles , 2001, Neural Networks.

[35]  Hiok Chai Quek,et al.  GenSo-EWS: a novel neural-fuzzy based early warning system for predicting bank failures , 2004, Neural Networks.

[36]  Stephen Grossberg,et al.  Adaptive pattern classification and universal recoding: II. Feedback, expectation, olfaction, illusions , 1976, Biological Cybernetics.

[37]  R. Fullér On fuzzy reasoning schemes , 1999 .

[38]  George J. Klir,et al.  Fuzzy sets and fuzzy logic - theory and applications , 1995 .

[39]  Richard S. Sutton,et al.  Reinforcement Learning: An Introduction , 1998, IEEE Trans. Neural Networks.

[40]  Lotfi A. Zadeh,et al.  Fuzzy logic, neural networks, and soft computing , 1993, CACM.

[41]  L. Zadeh Calculus of fuzzy restrictions , 1996 .

[42]  C. Rosenow,et al.  Monitoring gene expression using DNA microarrays. , 2000, Current opinion in microbiology.

[43]  Ruowei Zhou,et al.  Antiforgery: a novel pseudo-outer product based fuzzy neural network driven signature verification system , 2002, Pattern Recognit. Lett..

[44]  Nikola K. Kasabov,et al.  DENFIS: dynamic evolving neural-fuzzy inference system and its application for time-series prediction , 2002, IEEE Trans. Fuzzy Syst..

[45]  Chin-Teng Lin,et al.  An ART-based fuzzy adaptive learning control network , 1997, IEEE Trans. Fuzzy Syst..

[46]  Simon Lin,et al.  Methods of microarray data analysis III , 2002 .

[47]  Danh V. Nguyen,et al.  Tumor classification by partial least squares using microarray gene expression data , 2002, Bioinform..

[48]  Michael Q. Zhang,et al.  Current Topics in Computational Molecular Biology , 2002 .

[49]  J. Mendel Uncertain Rule-Based Fuzzy Logic Systems: Introduction and New Directions , 2001 .

[50]  Michel Pasquier,et al.  POPFNN-CRI(S): pseudo outer product based fuzzy neural network using the compositional rule of inference and singleton fuzzifier , 2003, IEEE Trans. Syst. Man Cybern. Part B.

[51]  Jyh-Shing Roger Jang,et al.  ANFIS: adaptive-network-based fuzzy inference system , 1993, IEEE Trans. Syst. Man Cybern..

[52]  GrossbergS. Adaptive pattern classification and universal recoding , 1976 .

[53]  Philipp Slusallek,et al.  Introduction to real-time ray tracing , 2005, SIGGRAPH Courses.

[54]  W. Hiddemann,et al.  Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. , 2000, Blood.

[55]  Zohar Yakhini,et al.  Clustering gene expression patterns , 1999, J. Comput. Biol..

[56]  Hiroshi Motoda,et al.  Feature Selection for Knowledge Discovery and Data Mining , 1998, The Springer International Series in Engineering and Computer Science.

[57]  Philip M. Long,et al.  Optimal gene expression analysis by microarrays. , 2002, Cancer cell.

[58]  C. S. George Lee,et al.  Neural fuzzy systems: a neuro-fuzzy synergism to intelligent systems , 1996 .

[59]  Xizhao Wang,et al.  On the handling of fuzziness for continuous-valued attributes in decision tree generation , 1998, Fuzzy Sets Syst..

[60]  Ruowei Zhou,et al.  POPFNN: A Pseudo Outer-product Based Fuzzy Neural Network , 1996, Neural Networks.

[61]  J. Downing,et al.  Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. , 2002, Cancer cell.

[62]  Didier Dubois,et al.  Fuzzy sets and systems ' . Theory and applications , 2007 .

[63]  Detlef Nauck,et al.  Foundations Of Neuro-Fuzzy Systems , 1997 .

[64]  Nello Cristianini,et al.  Support vector machine classification and validation of cancer tissue samples using microarray expression data , 2000, Bioinform..

[65]  Kai Keng Ang,et al.  Improved MCMAC with momentum, neighborhood, and averaged trapezoidal output , 2000, IEEE Trans. Syst. Man Cybern. Part B.

[66]  C. Pui,et al.  Acute lymphoblastic leukemia. , 1998, The New England journal of medicine.

[67]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[68]  Philippe Vincke,et al.  Acute leukemia diagnosis aid using multicriteria fuzzy assignment methodology , 2001, Comput. Methods Programs Biomed..

[69]  Roded Sharan,et al.  Algorithmic approaches to clustering gene expression data , 2001 .

[70]  Nikola K. Kasabov,et al.  On-line learning, reasoning, rule extraction and aggregation in locally optimized evolving fuzzy neural networks , 2001, Neurocomputing.