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Engineering a Scalable Placement Heuristic for DNA Probe Arrays



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Engineering a Scalable Placement Heuristic for DNA Probe Arrays A B Kahng I I Mandoiu P Pevzner S Reda all UCSD A Zelikovsky GSU Outline DNA probe arrays and unwanted illumination Synchronous array design 2 D placement Asynchronous array design 3 D placement Experimental results Extensions Conclusions Outline DNA probe arrays and unwanted illumination Synchronous array design 2 D placement Asynchronous array design 3 D placement Experimental results Extensions Conclusions DNA Probe Arrays Used in wide range of genomic analyses Gene expression monitoring SNP mapping sequencing by hybridization Arrays with up to 1000x1000 probes in commercial use 108 probes envisioned for next generation arrays Highly scalable algorithms required for array design Simplified DNA Array Flow Probe Selection Mask Design Placement Embedding Mask Manufacturing Array Manufacturing Hybridization Experiment Analysis of Hybridization Intensities Gene sequences position of SNPs etc Soft Computational Domain Hard Biochemistry Domain Array Manufacturing Process Very Large Scale Immobilized Polymer Synthesis 1 Treat substrate with chemically protected linker molecules creating rectangular array 2 Selectively expose array sites to light 3 Light deprotects exposed molecules activating further synthesis Flush chip surface with solution of protected A C G T 4 Site size approx 10x10 microns Binding occurs at previously deprotected sites Repeat steps 2 3 until desired probes are synthesized Photo Deprotection Step Our concern diffraction unwanted illumination yield decrease CG AC G AC ACG AG CG AG C Placed probes Nucleotide deposition sequence ACG Probe Synthesis G M3 C M2 A M1 CG AC CG AG AC ACG G AG C CG AC G AC ACG AG CG AG C Placed probes Nucleotide deposition sequence ACG Measuring Unwanted Illumination G M3 C M2 border A M1 Unwanted illumination border length CG AC CG AG AC ACG G AG C Synchronous vs Asynchronous Synthesis 4 group a periodic deposition sequence T G C G G b Synchronous embedding of



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