Modeling and Estimation for Real-Time Microarrays

Microarrays are used for collecting information about a large number of different genomic particles simultaneously. Conventional fluorescent-based microarrays acquire data after the hybridization phase. During this phase, the target analytes (e.g., DNA fragments) bind to the capturing probes on the array and, by the end of it, supposedly reach a steady state. Therefore, conventional microarrays attempt to detect and quantify the targets with a single data point taken in the steady state. On the other hand, a novel technique, the so-called real-time microarray, capable of recording the kinetics of hybridization in fluorescent-based microarrays has recently been proposed. The richness of the information obtained therein promises higher signal-to-noise ratio, smaller estimation error, and broader assay detection dynamic range compared to conventional microarrays. In this paper, we study the signal processing aspects of the real-time microarray system design. In particular, we develop a probabilistic model for real-time microarrays and describe a procedure for the estimation of target amounts therein. Moreover, leveraging on system identification ideas, we propose a novel technique for the elimination of cross hybridization. These are important steps toward developing optimal detection algorithms for real-time microarrays, and to understanding their fundamental limitations.

[1]  D. Botstein,et al.  A gene expression database for the molecular pharmacology of cancer , 2000, Nature Genetics.

[2]  J. Barrett,et al.  Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. , 1999, Cancer research.

[3]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[4]  I. Shmulevich,et al.  Computational and Statistical Approaches to Genomics , 2007, Springer US.

[5]  Dan V. Nicolau,et al.  Microarray technology and its applications , 2005 .

[6]  P. Brown,et al.  A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. , 1996, Genome research.

[7]  Jaakko Astola,et al.  Microarray quality control , 2004 .

[8]  P. Brown,et al.  Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Shirley Dex,et al.  JR 旅客販売総合システム(マルス)における運用及び管理について , 1991 .

[10]  Wei Zhang,et al.  Microarray Quality Control: Zhang/Microarray Quality Control , 2005 .

[11]  J Marx,et al.  DNA Arrays Reveal Cancer in Its Many Forms , 2000, Science.

[12]  J. Baldeschwieler,et al.  Real-time detection of DNA hybridization and melting on oligonucleotide arrays by using optical wave guides. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  G. Grinstein,et al.  Modeling of DNA microarray data by using physical properties of hybridization , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  L. Penland,et al.  Use of a cDNA microarray to analyse gene expression patterns in human cancer , 1996, Nature Genetics.

[15]  D. Kelso,et al.  Real-time measurements of DNA hybridization on microparticles with fluorescence resonance energy transfer. , 1999, Analytical biochemistry.

[16]  Signal Processing for Real-Time DNA Microarrays , 2007, 2007 Conference Record of the Forty-First Asilomar Conference on Signals, Systems and Computers.

[17]  Thomas Kailath,et al.  ESPRIT-estimation of signal parameters via rotational invariance techniques , 1989, IEEE Trans. Acoust. Speech Signal Process..

[18]  R. D. DeGroat,et al.  Exponential parameter estimation In the presence of known components and noise , 1994 .

[19]  Gordon K. Smyth,et al.  A Modified Prony Algorithm for Exponential Function Fitting , 1995, SIAM J. Sci. Comput..

[20]  Babak Hassibi,et al.  A statistical model for microarrays, optimal estimation algorithms, and limits of performance , 2006, IEEE Transactions on Signal Processing.

[21]  Aaas News,et al.  Book Reviews , 1893, Buffalo Medical and Surgical Journal.

[22]  G. Gibson,et al.  Microarray Analysis , 2020, Definitions.

[23]  R. Stoughton,et al.  Experimental annotation of the human genome using microarray technology , 2001, Nature.

[24]  M. Bittner,et al.  Expression profiling in cancer using cDNA microarrays , 1999, Electrophoresis.

[25]  M Schena,et al.  Microarrays: biotechnology's discovery platform for functional genomics. , 1998, Trends in biotechnology.

[26]  J. Kononen,et al.  Tissue microarrays for high-throughput molecular profiling of tumor specimens , 1998, Nature Medicine.

[27]  T. Owa [Drug target validation and identification of secondary drug target effects using DNA microarrays]. , 2007, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[28]  J. SantaLucia,et al.  A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[29]  A. Blanchard,et al.  Sequence to array: Probing the genome's secrets , 1996, Nature Biotechnology.

[30]  Christian A. Rees,et al.  Systematic variation in gene expression patterns in human cancer cell lines , 2000, Nature Genetics.

[31]  A. Blanchard,et al.  High-density oligonucleotide arrays , 1996 .

[32]  J. SantaLucia,et al.  The thermodynamics of DNA structural motifs. , 2004, Annual review of biophysics and biomolecular structure.

[33]  Y. Tu,et al.  Quantitative noise analysis for gene expression microarray experiments , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[34]  A. Swindlehurst,et al.  Subspace-based signal analysis using singular value decomposition , 1993, Proc. IEEE.