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Genome Technology Contents | Zoom in | Zoom out For navigation instructions please click here Search Issue | Next Page This month in Genome Technology Also inside this month’s Genome Technology • STRUCTURAL VARIATION The latest findings and approaches to under- standing copy number variation regions and what they mean. • METABOLOMICS Work is underway to improve the technology and analytical tools needed to understand phenotype. • CASE STUDY Researchers aim for molecular diagnostics to decipher the mystery of metastatic carcinomas of unknown primary. • CLINICAL Q&A: Gurvaneet Randhawa The genomics advisor opines on evidence- based medicine. LOG ON NOW AT WWW.GENOME-TECHNOLOGY.COM RECENT RESULTS FROM GT POLLS Explore all of our exclusive new resources for molecular biologists: How do you keep up with research in your field? THE DAILY SCAN — Our editors’ daily picks of what’s worth reading on the Web I rely on PubMed. What else THE FORUM — Where scientists can inquire and comment on research, tools, is there? .............................................. 68% and other topics I go online, to community-based sites PODCASTS — Hear the full comments – in their own voices – of researchers like FriendFeed and blogs. ................. 10% interviewed in Genome Technology Magazine I use referrals from other scientists. ...... 4% POLLS — Make your opinions known on topics from the sublime to the ridiculous I stick to the basics: Nature and ARCHIVE — Magazine subscribers can read every word of every article we Science. ................................................ 18% have ever published Contents | Zoom in | Zoom out For navigation instructions please click here Search Issue | Next Page A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS 1000-Series Thermal Cyclers WE THINK YOU SHOULD BE ABLE TO OPTIMIZE ON THE FLY Convenience Is What Happens When You Rethink PCR Change the way you think about PCR with Bio-Rad’s new family of thermal cyclers. Wouldn’t you rather optimize your reactions in minutes and not days? With Bio-Rad’s new 1000-series thermal cyclers, optimizing on the fl y is just the beginning. Q Easily interchangeable reaction modules meet any experimental or throughput need Q Reduced-mass sample blocks increase ramp rates and reduce run times Q Thermal gradient lets you incubate each row at a different temperature for fast protocol optimization When you rethink PCR, you realize how easy it should be. For more information, visit us on the Web at www.bio-rad.com/pcr Purchase of this instrument conveys a limited non-transferable immunity from suit for the purchaser’s own internal research and development and for use in applied fi elds other than Human In Vitro Diagnostics under one or more of U.S. Patents Nos. 5,656,493, 5,333,675, 5,475,610 (claims 1, 44, 158, 160–163 and 167 only), and 6,703,236 (claims 1–7 only), or corresponding claims in their non-U.S. counterparts, owned by Applera Corporation. No right is conveyed expressly, by implication or by estoppel under any other patent claim, such as claims to apparatus, reagents, kits, or methods such as 5’ nuclease methods. Further information on purchasing licenses may be obtained by contacting the Director of Licensing, Applied Biosystems, 850 Lincoln Centre Drive, Foster City, California 94404, USA. To find your local sales office, visit www.bio-rad.com/contact/ Visit us on the Web at discover.bio-rad.com In the U.S., call toll free at 1-800-4BIORAD (1-800-424-6723) A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS BONUS: ARRAY CGH TECH GUIDE SEPTEMBER 2008 THE ARTOF SPLICING Scientists work to unravel alternative splicing Copy Number Variation Advances in Metabolomics Informatics for Glycomics DIANE LIPSCOMBE OF BROWN AND HARVARD’S MICHAEL WOLFE A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS _________________________________ Seize the Genome NimbleGen Sequence Capture Arrays and Service Maximize the power of next-generation sequencing by capturing and enriching specific regions of interest for targeted resequencing. ■ Target Specific Regions of Interest Capture up to 5 Mb total sequence on a single array with high coverage and specificity. ■ Reduce Cost Significantly reduce time and cost compared to laborious and limiting PCR-based methods. ■ Generate Data with Confidence Ensure system performance prior to sequencing with built-in QC probes. ■ Customize Each Capture Design Specify the array design to capture contiguous genomic regions or thousands of exons in parallel. Figure 1: NimbleGen Sequence Capture Protocol 1. The genomic DNA sample is fragmented. 2. The sample is To seize command of your sequencing project, hybridized to a custom NimbleGen Sequence Capture array. 3. Unbound fragments are removed. 4. The target-enriched visit www.nimblegen.com/seqcap pool is eluted and amplified. 5. The enriched sample is ready or call (877) NimbleGen / (608) 218-7600 for processing in the GS FLX sample processing workflow. Roche Diagnostics Roche Applied Science 454, 454 LIFE SCIENCES, and 454 SEQUENCING are trademarks of 454 Life Sciences Corporation, Indianapolis, Indiana Branford, CT, USA, a Roche company. © 2008 Roche Diagnostics. All rights reserved. A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS SEPTEMBER 2008 Contents “We’ve long thought that the expression of different splice isoforms probably underlies a lot of the differential effects of drugs in different pathways.” Diane Lipscombe, Page 41 Metabolomics Structural Alternative Taming Metabolites variation splicing Metabolomics studies inch scientists ever closer Counting on A Complexity that to understanding phenotype. Copy Number Goes Beyond Genes But to really make progress, Research into copy number Most genes are subject pioneers are working on variation is highlighting just to alternative splicing, but improving the technology how complex genomic differ- it’s still early days in under- and analytical tools ences are. A glimpse at the standing the phenomenon of the field. latest findings and approaches across pathways or on a BY CIARA CURTIN to understanding CNV regions genome-wide scale. A look and what they mean. at some pioneers in the field BY MEREDITH SALISBURY and the technologies they’ve commandeered to make sense of it. 31 BY JEANENE SWANSON 37 40 On The Cover 40 The Art of Splicing 37 Copy Number Variation 31 Advances in Metabolomics 25 Informatics for Glycomics COVER AND TOP RIGHT PHOTOS: SAM RILEY SEPTEMBER 2008 GENOME TECHNOLOGY 3 A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS OPEN TO: Putting genomic variation in your sights. Growing numbers of scientists are turning to Copy Number Variants (CNVs) to gain a greater understanding of the links between genetic variation and disease. Agilent’s proven CGH platform, combined with a newly expanded and validated probe database, enables you to interrogate CNV regions with greater sensitivity and specifi city. DNA Analytics software provides you with a valuable new way to explore and visualize patterns of human genetic variation. Look into Agilent CNV microarrays— and see the whole picture on structural variation. Visualize patterns 155.398 Mb of variation q33 with Learn what CNVs can mean q33.2 DNA Analytics to your research by visiting q34 155.418 Mb CNV_Locus 0409 CNV_Locus 0409 www.opengenomics.com/cnv 55.439 Mb © Agilent Technologies, Inc. 2008 A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS A Genome Technology Previous Page | Contents | Zoom in | Zoom out | Front Cover | Search Issue | Next Page BEF MaGS SEPTEMBER 2008 Contents 10 28 61 Markers In every issue Upstream GWAS ................................................10 PRIMER ..............................................7 SEQUENCING..................................49 NHGRI issues $31M to The simple life? Not for us Barcode of Life project follow-up SNP research leans on sequencing WHERE ARE THEY NOW?................9 SAMPLE PREP..................................11 ImmunoPCR, microarray PROTEOMICS ..................................51 Marziali’s tech for DNA diagnostics, and a whole Satoris to launch purification tackles the new breed of institute Alzheimer’s test worst of contamination ZEITGEIST ........................................18 RNA INTERFERENCE ....................53 GENE EXPRESSION........................12 Something to talk about Tacere evaluates new Cancer consortium traces drug opportunities signature for lung cancer CAREERS ........................................20 recurrence Savvy strategies in a BIOINFORMATICS ..........................55 budget crunch Scientists debate publishing MICROFLUIDICS..............................13 future RainDance readies to ship INFORMATICS INSIDER ................23 early-access version of Homology: genealogy for genes
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