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NCI - R01s, SPORE DOE DARPA Whitaker Foundation P.O’B Montgomery Distinguished Chair Hewlett-Packard Texas Instruments Beckman Instruments.
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NCI - R01s, SPORE DOE DARPA Whitaker Foundation P.O’B Montgomery Distinguished Chair Hewlett-Packard Texas Instruments Beckman Instruments John Minna, M.D., Ron Butow, Ph.D., Roger Schultz, Ph.D.Stephen Johnston, Ph.D., Sandy Williams, M.D. Ralph Shohet,, M.D, Jonathan Uhr, M.D., Ward Wakeland,Ph.D…... Jonathan Wren, Trey Fondon, Ashwini Pande, Kari Kukanskis, Greg Miller, Varshal Dave’, Robert Balog, Walker Hale, Chuck Epstein, Nikki Dossman,Tiffany Murphy, Gina Mele, David Mittleman, & a lot of summer interns, etc. Funders Collaborators and Doers
3p21.3 Allelotyping Markers (POMPOUS) 1.1* P1.2† 1.2* P1.3¥ 11.1* 20.2† 17.1† 1.3* 19.1* 6.3† 13.4^ 22* 7.1∆ P1.4¥ 11.2* 17.2¥ 12.1* 19.2† P1.5* 7.2† 4.1* 11.4^ 17.4† 2.1* 8.1* 4.2† 2.2* P1.6† 8.2* 4.3¥ P1.7~ 8.3^ 4.4* 1 2 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 22 P3938 5 Centromeric Telomeric 750 kb * dinucleotide repeat ^ trinucleotide repeat † tetranucleotide repeat ¥ pentanucleotide repeat ∆ hexanucleotide repeat ~ 10mer repeat
PANORAMA Integrated Analysis on The WWW BLAST CpG islands GenScan Repeats POMPOUS …….. SNooP (soon)
Gene expression and re-sequencing analysis Virtual Expression Arrays Array Readout, Databasing & Analysis Custom Array Design Custom Array Fabrication Other Input - Including Commercial collections MerMade, GenePix, ScanArray 3000, MAGNA & DOC ARID ORACLE, Excel Macros, AI based tools VEA
40 slides/day, $35k Plans/software on the web Spotted Array Construction and Readout MerMade Oligo Synthesizer Hyperspectral Imaging Sequencer, Array Reader, Microscope
Mouse Cardiac - Yeast Array Cross Hybridization 2:1 ReducedExpression (<~ 1400) Normal Heart mRNA 1:1 0.5:1 Increased Expression (<~500) Hypertrophic Heart mRNA
Hyperspectral Imaging (used in UTSW’s sequencer, array scanner and microscope) is prominent in earth orbit satellites. MISTI
Hyperspectral Imaging Cytogenetics Microscope • Olympus inverted microscope • ARC imaging spectrograph/Photometrix camera • Ar+, HeNe, SS, Pulsed N2 doubled dye lasers, Hg burner • Mac acquisition system • Scanalytics slide mover • UTSW custom ‘C’ software • UTSW custom fluorescent probes
Detection of Blood Born Cancer Cells with Fluorescent Labels - 5 colors
UTSW’s Next Generation Arrays - Digital Optical Chemistry The DOC Device is a machine capable of projecting UV light so that patterns of photochemical reactions of great detail can be done. This prototype machine has demonstrated the ability to make proof-of-principle oligonucleotide arrays, like those on Affymetix GeneChips that can be used to perform a large number of sequence or expression analysis on a single chip. - A marriage of Affymetrix and Texas Instruments Technologies
How an image is created Light Source Light Source Light Source Light Source Light Source Light Source Light Source Projection Lens Projection Lens Projection Lens Projection Lens Projection Lens Projection Lens Projection Lens Light Absorber Light Absorber Light Absorber Light Absorber Light Absorber Light Absorber Light Absorber 3 DMD Micromirrors 3 DMD Micromirrors 3 DMD Micromirrors 3 DMD Micromirrors 3 DMD Micromirrors 3 DMD Micromirrors 3 DMD Micromirrors (Actual Top View) (Actual Top View) (Actual Top View) (Actual Top View) (Actual Top View) (Actual Top View) (Actual Top View)
Digital Optical Chemistry -Custom Oligonucleotide Arrays Cy5 labeled 2-mer • Prototype demonstrated • TI DMD/DLP based projection system • Automated production unit beginning testing • ~480,000 oligos max. in first prototype • Yeast ORFs test array • Array design software in development 192 microns
The Future • Informatics - • GeneXpert, Array Designer • Array Technology • Exploit MAGNA • DOC applications • DOC preparative synthesis • Technology for Custom Cancer Vaccines - genomics/expression approach