Application of Wavelet Packet Transform to detect genetic polymorphisms by the analysis of inter-Alu PCR patterns

BackgroundThe analysis of Inter-Alu PCR patterns obtained from human genomic DNA samples is a promising technique for a simultaneous analysis of many genomic loci flanked by Alu repetitive sequences in order to detect the presence of genetic polymorphisms. Inter-Alu PCR products may be separated and analyzed by capillary electrophoresis using an automatic sequencer that generates a complex pattern of peaks. We propose an algorithmic method based on the Haar-Walsh Wavelet Packet Transformation (WPT) for an efficient detection of fingerprint-type patterns generated by PCR-based methodologies. We have tested our algorithmic approach on inter-Alu patterns obtained from the genomic DNA of three couples of monozygotic twins, expecting that the inter-Alu patterns of each twins couple will show differences due to unavoidable experimental variability. On the contrary the differences among samples of different twins are supposed to originate from genetic variability. Our goal is to automatically detect regions in the inter-Alu pattern likely associated to the presence of genetic polymorphisms.ResultsWe show that the WPT algorithm provides a reliable tool to identify sample to sample differences in complex peak patterns, reducing the possible errors and limits associated to a subjective evaluation. The redundant decomposition of the WPT algorithm allows for a procedure of best basis selection which maximizes the pattern differences at the lowest possible scale. Our analysis points out few classifying signal regions that could indicate the presence of possible genetic polymorphisms.ConclusionsThe WPT algorithm based on the Haar-Walsh wavelet is an efficient tool for a non-supervised pattern classification of inter-ALU signals provided by a genetic analyzer, even if it was not possible to estimate the power and false positive rate due to the lacking of a suitable data base. The identification of non-reproducible peaks is usually accomplished comparing different experimental replicates of each sample. Moreover, we remark that, albeit we developed and optimized an algorithm able to analyze patterns obtained through inter-Alu PCR, the method is theoretically applicable to whatever fingerprint-type pattern obtained analyzing anonymous DNA fragments through capillary electrophoresis, and it could be usefully applied on a wide range of fingerprint-type methodologies.

[1]  D. Labuda,et al.  Detection of a mutator phenotype in cancer cells by inter-Alu polymerase chain reaction. , 1996, Cancer research.

[2]  D. Labuda,et al.  Linkage mapping by simultaneous screening of multiple polymorphic loci using Alu oligonucleotide-directed PCR. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D. Labuda,et al.  Genome fingerprinting by simple sequence repeat (SSR)-anchored polymerase chain reaction amplification. , 1994, Genomics.

[4]  D. Valle,et al.  Mobile Interspersed Repeats Are Major Structural Variants in the Human Genome , 2010, Cell.

[5]  W. Coleman,et al.  Alu profiling of primary and metastatic nonsmall cell lung cancer. , 2003, Experimental and molecular pathology.

[6]  Michael Frazier.  Wavelets on ℤ , 2000 .

[7]  Robert R. Klevecz,et al.  Dynamic architecture of the yeast cell cycle uncovered by wavelet decomposition of expression microarray data , 2000, Functional & Integrative Genomics.

[8]  J. Welsh,et al.  Fingerprinting genomes using PCR with arbitrary primers. , 1990, Nucleic acids research.

[9]  Andrew F. Neuwald,et al.  Natural Mutagenesis of Human Genomes by Endogenous Retrotransposons , 2010, Cell.

[10]  M. Cardelli.  Alu PCR. , 2011, Methods in molecular biology.

[11]  International Human Genome Sequencing Consortium.  Initial sequencing and analysis of the human genome , 2001, Nature.

[12]  Pietro Liò,et al.  Wavelets in bioinformatics and computational biology: state of art and perspectives , 2003, Bioinform..

[13]  P. Vos,et al.  AFLP: a new technique for DNA fingerprinting. , 1995, Nucleic acids research.

[14]  S. Sinha,et al.  Aberrant methylation and associated transcriptional mobilization of Alu elements contributes to genomic instability in hypoxia , 2009, Journal of cellular and molecular medicine.

[15]  D. Labuda,et al.  Overall informativity, OI, in DNA polymorphisms revealed by inter-Alu PCR: detection of genomic rearrangements. , 1996, Genomics.

[16]  T. Darden,et al.  Biased distribution of inverted and direct Alus in the human genome: implications for insertion, exclusion, and genome stability. , 2001, Genome research.

[17]  S. Sinha,et al.  Inter‐alu PCR detects high frequency of genetic alterations in glioma cells exposed to sub‐lethal cisplatin , 2005, International journal of cancer.

[18]  C. Burks,et al.  The distribution of interspersed repetitive DNA sequences in the human genome. , 1989, Genomics.

[19]  A. Jensen,et al.  Ripples in Mathematics - The Discrete Wavelet Transform , 2001 .

[20]  Dapeng Zhang,et al.  Inter- and intra-specific variation among five Erythroxylum taxa assessed by AFLP. , 2005, Annals of botany.

[21]  H. Khan,et al.  Use of RAPD fingerprinting for discriminating two populations of Hilsa shad (Tenualosa ilisha Ham.) from inland rivers of Bangladesh. , 2003, Journal of biochemistry and molecular biology.

[22]  Ronald R. Coifman,et al.  IMPROVED LOCAL DISCRIMINANT BASES USING EMPIRICAL PROBABILITY DENSITY ESTIMATION , 1996 .

[23]  K. Livak,et al.  DNA polymorphisms amplified by arbitrary primers are useful as genetic markers. , 1990, Nucleic acids research.

[24]  D. Labuda,et al.  Alumorphs--human DNA polymorphisms detected by polymerase chain reaction using Alu-specific primers. , 1990, Genomics.

[25]  Pietro Liò,et al.  Finding pathogenicity islands and gene transfer events in genome data , 2000, Bioinform..

[26]  Chun-Ting Zhang,et al.  Identification of isochore boundaries in the human genome using the technique of wavelet multiresolution analysis. , 2003, Biochemical and biophysical research communications.

[27]  A. Pardee,et al.  Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. , 1992, Science.

[28]  C. Franceschi,et al.  Increase of homozygosity in centenarians revealed by a new inter-Alu PCR technique , 2001, Experimental Gerontology.

[29]  Ronald R. Coifman,et al.  Entropy-based algorithms for best basis selection , 1992, IEEE Trans. Inf. Theory.

[30]  A. Mighell,et al.  Alu sequences , 1997, FEBS letters.

[31]  D. Ledbetter,et al.  Alu polymerase chain reaction: a method for rapid isolation of human-specific sequences from complex DNA sources. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Srivastava,et al.  Molecular assessment of genetic diversity in mung bean germplasm , 2008, Journal of Genetics.

[33]  Claudio Franceschi,et al.  A polymorphism of the YTHDF2 gene (1p35) located in an Alu-rich genomic domain is associated with human longevity. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[34]  Ingrid Daubechies,et al.  Ten Lectures on Wavelets , 1992 .

[35]  M. Hollingsworth,et al.  Alu‐polymerase chain reaction genomic fingerprinting technique identifies multiple genetic loci associated with pancreatic tumourigenesis , 1997, Genes, chromosomes & cancer.

[36]  Ju Wang,et al.  Normalization of cDNA microarray data using wavelet regressions. , 2004, Combinatorial chemistry & high throughput screening.