FM-test: a fuzzy-set-theory-based approach to differential gene expression data analysis

BackgroundMicroarray techniques have revolutionized genomic research by making it possible to monitor the expression of thousands of genes in parallel. As the amount of microarray data being produced is increasing at an exponential rate, there is a great demand for efficient and effective expression data analysis tools. Comparison of gene expression profiles of patients against those of normal counterpart people will enhance our understanding of a disease and identify leads for therapeutic intervention.ResultsIn this paper, we propose an innovative approach, fuzzy membership test (FM-test), based on fuzzy set theory to identify disease associated genes from microarray gene expression profiles. A new concept of FM d-value is defined to quantify the divergence of two sets of values. We further analyze the asymptotic property of FM-test, and then establish the relationship between FM d-value and p-value. We applied FM-test to a diabetes expression dataset and a lung cancer expression dataset, respectively. Within the 10 significant genes identified in diabetes dataset, six of them have been confirmed to be associated with diabetes in the literature and one has been suggested by other researchers. Within the 10 significantly overexpressed genes identified in lung cancer data, most (eight) of them have been confirmed by the literatures which are related to the lung cancer.ConclusionOur experiments on synthetic datasets show that FM-test is effective and robust. The results in diabetes and lung cancer datasets validated the effectiveness of FM-test. FM-test is implemented as a Web-based application and is available for free at http://database.cs.wayne.edu/bioinformatics.

[1]  Sophie Rome,et al.  Microarray Profiling of Human Skeletal Muscle Reveals That Insulin Regulates ∼800 Genes during a Hyperinsulinemic Clamp* 210 , 2003, The Journal of Biological Chemistry.

[2]  Debashis Kushary,et al.  Bootstrap Methods and Their Application , 2000, Technometrics.

[3]  Isaac Kohane,et al.  Differences in Gene Expression Profiles of Diabetic and Nondiabetic Patients Undergoing Cardiopulmonary Bypass and Cardioplegic Arrest , 2004, Circulation.

[4]  Y. Habib,et al.  Serum electrolytes in diabetic patients and the effect of insulin treatment. , 1959, The Journal of the Egyptian Medical Association.

[5]  B. Potter,et al.  Mechanisms involved in alpha6beta1-integrin-mediated Ca(2+) signalling. , 2001, Cellular signalling.

[6]  Anna Maria D'Erchia,et al.  Connecting p63 to Cellular Proliferation: The Example of the Adenosine Deaminase Target Gene , 2006, Cell cycle.

[7]  R A Laskey,et al.  Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions , 2003, British Journal of Cancer.

[8]  A. Berger FUNDAMENTALS OF BIOSTATISTICS , 1969 .

[9]  Ansgar Schmidt,et al.  Differential expression of desmosomal plakophilins in various types of carcinomas: correlation with cell type and differentiation. , 2006, Human pathology.

[10]  Shiladitya Sengupta,et al.  Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. , 2007, Carcinogenesis.

[11]  Michael G. Roper,et al.  Islet secretory defect in insulin receptor substrate 1 null mice is linked with reduced calcium signaling and expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2b and -3. , 2004, Diabetes.

[12]  Sophie Rome,et al.  Microarray profiling of human skeletal muscle reveals that insulin regulates approximately 800 genes during a hyperinsulinemic clamp. , 2003, The Journal of biological chemistry.

[13]  Kay Nieselt,et al.  Progression-specific genes identified by expression profiling of matched ductal carcinomas in situ and invasive breast tumors, combining laser capture microdissection and oligonucleotide microarray analysis. , 2006, Cancer research.

[14]  C. Mitchell,et al.  The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2. , 2005, The international journal of biochemistry & cell biology.

[15]  Jin-Xiong She,et al.  Molecular Pathways Altered by Insulin B9‐23 Immunization , 2004, Annals of the New York Academy of Sciences.

[16]  Shinichiro Wachi,et al.  Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues , 2005, Bioinform..

[17]  Andreas H. Guse,et al.  Mechanisms involved in α6β1-integrin-mediated Ca2+ signalling , 2001 .

[18]  S. Zhao,et al.  Identification and characterization of the human HCG V gene product as a novel inhibitor of protein phosphatase-1. , 1998, Biochemistry.

[19]  R. Houghton,et al.  Multigene real-time PCR detection of circulating tumor cells in peripheral blood of lung cancer patients. , 2006, Anticancer research.

[20]  C. Bogardus,et al.  Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians , 2002, Diabetologia.

[21]  V. Capelozzi,et al.  Expression of p63, keratin 5/6, keratin 7, and surfactant-A in non-small cell lung carcinomas. , 2006, Human pathology.

[22]  U. Krawinkel,et al.  Characterization of eukaryotic protein L7 as a novel autoantigen which frequently elicits an immune response in patients suffering from systemic autoimmune disease. , 1994, Immunobiology.

[23]  D. Harlan,et al.  Oligonucleotide Microarray Analysis of Intact Human Pancreatic Islets: Identification of Glucose-Responsive Genes and a Highly Regulated TGFβ Signaling Pathway , 2002 .

[24]  John R Yates,et al.  Maspin and tumor metastasis , 2006, IUBMB life.

[25]  Alex Mas,et al.  Overexpression of c‐myc in the liver prevents obesity and insulin resistance , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  C. Ronald Kahn Insulin Induces the Phosphorylation of Nucleolin , 1993 .

[27]  S. Grossberg,et al.  Leucine catabolism during the differentiation of 3T3-L1 cells. Expression of a mitochondrial enzyme system. , 1983, The Journal of biological chemistry.

[28]  Robert J Cerfolio,et al.  Differential expression and biodistribution of cytokeratin 18 and desmoplakins in non-small cell lung carcinoma subtypes. , 2002, Lung cancer.

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

[30]  C. Kahn,et al.  Insulin induces the phosphorylation of nucleolin. A possible mechanism of insulin-induced RNA efflux from nuclei. , 1993, The Journal of biological chemistry.

[31]  K. Nair,et al.  Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment. , 2002, Diabetes.

[32]  Yu Shyr,et al.  Significance of p63 amplification and overexpression in lung cancer development and prognosis. , 2003, Cancer research.