I invite you to learn about the ArrayTrack software for microarray data management, analysis, and interpretation at the FDA/NCTR’s Center for Toxicoinformatics.

 

 

DNA Microarrays - A technology that is reshaping molecular biology

It is widely believed that thousands of genes and their products (i.e., RNA and proteins) in a given living organism function in a complicated and orchestrated way that creates the mystery of life. However, traditional methods in molecular biology generally work on a "one gene in one experiment" basis, which means that the throughput is very limited and the "whole picture" of gene function is hard to obtain. In the past several years, a new technology, called DNA microarray, has attracted tremendous interests among biologists. This technology promises to monitor the whole genome on a single chip so that researchers can have a better picture of the interactions among thousands of genes simultaneously.

Terminologies that have been used in the literature to describe this technology include, but not limited to: biochip, DNA chip, DNA microarray, and gene array. Affymetrix, Inc. owns a registered trademark, GeneChip®, which refers to its high density, oligonucleotide-based DNA arrays. However, in some articles appeared in professional journals, popular magazines, and the WWW the term "gene chip(s)" has been used as a general terminology that refers to the microarray technology. Affymetrix strongly opposes such usage of the term "gene chip(s)". More recently, I prefer the term "genome chip", indicating that this technology is meant to monitor the whole genome on a single chip. GenomeChip would also include the increasingly important and feasible protein chip technology.

Base-pairing (i.e., A-T and G-C for DNA; A-U and G-C for RNA) or hybridization is the underlining principle of DNA microarray.

An array is an orderly arrangement of samples. It provides a medium for matching known and unknown DNA samples based on base-pairing rules and automating the process of identifying the unknowns. An array experiment can make use of common assay systems such as microplates or standard blotting membranes, and can be created by hand or make use of robotics to deposit the sample. In general, arrays are described as macroarrays or microarrays, the difference being the size of the sample spots. Macroarrays contain sample spot sizes of about 300 microns or larger and can be easily imaged by existing gel and blot scanners. The sample spot sizes in microarray are typically less than 200 microns in diameter and these arrays usually contains thousands of spots. Microarrays require specialized robotics and imaging equipment that generally are not commercially available as a complete system.

DNA microarray, or DNA chips are fabricated by high-speed robotics, generally on glass but sometimes on nylon substrates, for which probes* with known identity are used to determine complementary binding, thus allowing massively parallel gene expression and gene discovery studies. An experiment with a single DNA chip can provide researchers information on thousands of genes simultaneously - a dramatic increase in throughput. (*Note: In the literature there exist at least two confusing nomenclature systems for referring to hybridization partners. Both use common terms: "probes" and "targets". According to the nomenclature recommended by B. Phimister of Nature Genetics, a "probe" is the tethered nucleic acid with known sequence, whereas a "target" is the free nucleic acid sample whose identity/abundance is being detected. This site follows that recommendation. See Nature Genetics volume 21 supplement pp 1 - 60, 1999, which is freely accessable.

There are two major application forms for the DNA microarray technology: 1) Identification of sequence (gene / gene mutation); and 2) Determination of expression level (abundance) of genes.

There are two variants* of the DNA microarray technology, in terms of the property of arrayed DNA sequence with known identity:

Format I: probe cDNA (500~5,000 bases long) is immobilized to a solid surface such as glass using robot spotting and exposed to a set of targets either separately or in a mixture. This method, "traditionally" called DNA microarray, is widely considered as developed at Stanford University. A recent article by R. Ekins and F.W. Chu (Microarrays: their origins and applications. Trends in Biotechnology, 1999, 17, 217-218) seems to provide some generally forgotten facts.

Format II: an array of oligonucleotide (20~80-mer oligos) or peptide nucleic acid (PNA) probes is synthesized either in situ (on-chip) or by conventional synthesis followed by on-chip immobilization. The array is exposed to labeled sample DNA, hybridized, and the identity/abundance of complementary sequences are determined. This method, "historically" called DNA chips, was developed at Affymetrix, Inc. , which sells its photolithographically fabricated products under the GeneChip® trademark. Many companies are manufacturing oligonucleotide based chips using alternative in-situ synthesis or depositioning technologies.

In the preparation of this Web site, "DNA microarray(s)" and "DNA chip(s)" are used interchangeably. But viewers should aware this technical difference.

* In addition, microfluidics-based chip or laboratory-on-a-chip systems are also listed in this Web site.

The microarray (DNA chip) technology is having a significant impact on genomics study. Many fields, including drug discovery and toxicological research, will certainly benefit from the use of DNA microarray technology. View an example of the microarray image (38K).

For a very well-written introduction on the steps involved in a microarray experiment, visit Jeremy Buhler's Anatomy of a Comparative Gene Expression Study

An excellent collection of Genomics Glossaries (including a Microarrays Glossary) is being maintained by Mary Chitty of Cambridge Healthtech Institute.

Design of a DNA Microarray System

There are several steps in the design and implementation of a DNA microarray experiment. Many strategies have been investigated at each of these steps. 1) DNA types; 2) Chip fabrication; 3) Sample preparation; 4) Assay; 5) Readout; and 6) Software (informatics)

Table 1. Steps in the design and implementation of a DNA microarray experiment

There are so many options and combinations, as can been seen from the number of companies involved in this business. It seems too early to judge who will be the winner(s) in this game. The forecast is further complicated by recent fights among companies on intellectual property issues.

Applications of DNA Microarray Technology

Gene discovery

(Many, many applications, to be listed)

Disease diagnosis

(Many, many applications, to be listed).
Many "microfluidics" devices (Chemical & Engineering News, February 22, 1999, 77(8):27-36; password required) fall in this category. Although they are not the "traditional" gene chip or microarray, I decided to list related links at this site because of their close connection and integration to the gene chip (microarray) technology.

Drug discovery: Pharmacogenomics

Why some drugs work better in some patients than in others? And why some drugs may even be highly toxic to certain patients? My favorite definition (modified): Pharmacogenomics is the hybridization of functional genomics and molecular pharmacology. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients.

Toxicological research: Toxicogenomics

Have you seen anybody using this terminology? Now let's try to give it a definition: Toxicogenomics is the hybridization of functional genomics and molecular toxicology. The goal of toxicogenomics is to find correlations between toxic responses to toxicants and changes in the genetic profiles of the objects exposed to such toxicants. First Preclinical Toxicity Application (Toxicology EXPRESS™ database using Gene Logic's Flow-thru Chip™ technology) between Wyeth-Ayerst Research and Gene Logic
An interesting article: Nuwaysir, E.F., Bittner, M., Trent, J., Barrett, J.C., and Afshari, C.A. Microarray and Toxicology: The Advent of Toxicogenomics. Molecular Carcinogenesis, 24:153-159(1999).
NIEHS sponsored a meeting on the application of DNA microarray in toxicology (EHP 1999).
NIEHS established the National Center for Toxicogenomics (NCT) in June 2000.

Articles on DNA Microarray Technology

1. Jenkins RE, Pennington SR. Arrays for protein expression profiling: towards a viable alternative to two-dimensional gel electrophoresis?

Proteomics. 2001 Jan;1(1):13-29. Review.

2. D. D. Shoemaker, E. E. Schadt, C. D. Armour, Y. D., He, P. Garrett-Engele, P. D. McDonagh, P. M. Loer ..., Experimental annotation of the human genome using microarray technology, Nature Volume 409 Number 6822 Page 922 - 927 (2001)
3. Kane MD, Jatkoe TA, Stumpf CR, Lu J, Thomas JD, Madore SJ, Assessment of the sensitivity and specificity of oligonucleotide (50mer) microarrays. Nucleic Acids Res 2000 Nov 15;28(22):4552-7. Abstract
4. G. MacBeath and S.L. Schreiber, Printing Proteins as Microarrays for High-Throughput Function Determination, Science 2000 September 8; 289(5485): p. 1760-1763. Abstract (New! Protein chip)
5. Taton TA, Mirkin CA, Letsinger RL.[Northwestern U.] Scanometric DNA array detection with nanoparticle probes.  Science. 2000 Sep 8; 289(5485):1757-60. Seem to offer great selectivity and sensitivity. Abstract
6. Jörg Reichert et al., Chip-Based Optical Detection of DNA Hybridization by Means of Nanobead Labeling, Anal. Chem., 72 (24), 6025 -6029, 2000. Abstract
7. Reinke V, Smith HE, Nance J, Wang J, Van Doren C, Begley R, Jones SJ, Davis EB, Scherer S, Ward S, Kim SK [Stanford] A global profile of germline gene expression in C. elegans. Mol Cell 2000 Sep;6(3):605-16. URL
8. Marx J. DNA Arrays Reveal Cancer in Its Many Forms. Science2000 September 8; 289: 1670-1672. (in News Focus)
9. DJ Lockhart and EA Winzeler. Genomics, gene expression and DNA arrays. Nature, 2000, 405(6788):827-836.
10. Cortese JD, The Array of Today: Biomolecule arrays become the 21st century's test tube, The Scientist 14[17]:25, Sep. 4, 2000 URL
11. Cortese JD, Array of Options: Instrumentation to exploint the DNA microarray explosion, The Scientist 14[11]:26, May. 29, 2000 URL
12. Fritz J, Baller MK, Lang HP, Rothuizen H, Vettiger P, Meyer E, Guntherodt H, Gerber C, Gimzewski JK. Translating biomolecular recognition into nanomechanics. Science. 2000 Apr 14;288(5464):316-8. [Medline]
13. Mark Schena (Ed.),  Microarray Biochip Technology, $49.95, Eaton Publishing Company, Distributed by TeleChem / arrayit.com
14. Scherf U, Ross DT, Waltham M, Smith LH, Lee JK, Tanabe L, Kohn KW, Reinhold WC, Myers TG, Andrews DT, Scudiero DA, Eisen MB, Sausville EA, Pommier Y, Botstein D, Brown PO, Weinstein JN. A gene expression database for the molecular pharmacology of cancer. Nat Genet. 2000 Mar;24(3):236-44. [Medline] [Authors' Web site]
15. Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van De Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D, Brown PO.  Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet. 2000 Mar;24(3):227-35. [Medline] [Authors' Web site]
16. Walt DR. Bead-based Fiber-Optic Arrays. Science, 2000 January 21; 287: 451-452. (in Tech.Sight)
17. Afshari CA, Nuwaysir EF, Barrett JC [NIEHS] Application of complementary DNA microarray technology to carcinogen identification, toxicology, and drug safety evaluation. Cancer Res 1999 Oct 1;59(19):4759-60
18. Gwynne P. and Page G. Microarray analysis: the next revolution in molecular biology. Science, 1999 August 6. (special advertising supplement; has a list of microarray-related companies)
19. Baldwin D, Crane V, Rice D. A comparison of gel-based, nylon filter and microarray techniques to detect differential RNA expression in plants. Curr Opin Plant Biol1999 Apr;2(2):96-103
20. Pollack JR, Perou CM, Alizadeh AA, Eisen MB, Pergamenschikov A, Williams CF, Jeffrey SS, Botstein D, Brown PO [Stanford] Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nat Genet 1999 Sep;23(1):41-6
21. Khan J, Saal LH, Bittner ML, Chen Y, Trent JM, Meltzer PS. Expression profiling in cancer using cDNA microarrays. Electrophoresis 1999 Feb;20(2):223-9
22. Gerhold D, Rushmore T, Caskey CT [Merck]. DNA chips: promising toys have become powerful tools. Trends Biochem Sci 1999 May;24(5):168-73
23. Ekins R. and Chu F.W. Microarrays: their origins and applications. Trends in Biotechnology, 1999, 17, 217-218.
24. Nuwaysir, E.F., Bittner, M., Trent, J., Barrett, J.C., and Afshari, C.A. Microarray and Toxicology: The Advent of Toxicogenomics. Molecular Carcinogenesis, 1999, 24:153-159.
25. Sinclair, B. Everything's Great When It Sits on a Chip - A bright future for DNA arrays, The Scientist, 1999 May 24, 13(11), 18-20.
26. Nature Genetics published a special issue (January 1999 Supplement), The Chipping Forecast. It's a collection of more than 10 reviews (60 pages) on different aspects of microarray analysis. All the reviews are freely available online.
27. Biochips: From Technologies to Markets, 2nd Edition, (IBC's D&MD Report , March 1999, 200+ Pages, 25+ Exhibits, 20+ Companies Profiled, $4,950!)
28. Schena, M. and Davis, R.W. Genes, Genomes and Chips. In DNA Microarrays: A Practical Approach (ed. M. Schena), Oxford University Press, Oxford, UK, 1999.
29. Marton MJ, DeRisi JL, Bennett HA, Iyer VR, Meyer MR, Roberts CJ, Stoughton R, Burchard J, Slade D, Dai H, Bassett DE Jr, Hartwell LH, Brown PO, Friend SH [Rosetta/Stanford]. Drug target validation and identification of secondary drug target effects using DNA microarrays. Nat Med. 1998 Nov;4(11):1293-301. [Medline] (convincing results on the utility of microarray technology for drug target validation and identification.)
30. Wang DG, Fan JB, ..., Lander ES, et al [MIT] Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 1998 May 15;280(5366):1077-82
31. Schena, M. and R.W. Davis. Parallel Analysis with Biological Chips. in PCR Methods Manual (eds. M. Innis, D. Gelfand, J. Sninsky), Academic Press, San Diego, 1998. (Sorry, I haven't seen it yet.)
32. Lemieux, B., Aharoni, A., and M. Schena. Overview of DNA Chip Technology.  Molecular Breeding 1998, 4, 277-289.
33. Schena, M., Heller, R.A., Theriault, T.P., Konrad, K., Lachenmeier, E., and Davis, R.W. Microarrays: biotechnology's discovery platform for functional genomics. Trends in Biotechnology 1998, 16, 301-306.
34. Service, R.F. Microchip arrays put DNA on the spot. Science 1998, 282(5388), 396-399.
35. Service, R.F. Coming soon: the pocket DNA sequencer. Science 1998, 282(5388), 399-401.
36. Kricka, L. Revolution on a Square Centimeter. Nature Biotechnology 1998, 16, 513.
37. Housman, D.; Ledley, F. Why pharmacogenomics? Why now? Nature Biotechnology 1998, 16(6), 492-493.
38. Ramsay, G. DNA chips - states-of-the-art. Nature Biotechnology 1998, 16(1), 40-44.
39. Marshall, A.; Hodgson, J.  DNA chips - an array of possibilities. Nature Biotechnology 1998, 16(1), 27-31.
40. Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998 Jul;4(7):844-847
41. Blanchard, A.P. (1998) Synthetic DNA Arrays; in Genetic Engineering, Vol. 20, pp. 111-123, edited by J.K. Setlow, Plenum Press, New York.
42. Proudnikov D, Timofeev E, Mirzabekov A [Argonne]. Immobilization of DNA in polyacrylamide gel for the manufacture of DNA and DNA-oligonucleotide microchips. Anal Biochem 1998 May 15;259(1):34-41
43. Chen JJ, Wu R, Yang PC, Huang JY, Sher YP, Han MH, Kao WC, Lee PJ, Chiu TF, Chang F, Chu YW, Wu CW, Peck K Profiling expression patterns and isolating differentially expressed genes by cDNA microarray system with colorimetry detection. Genomics 1998 Aug 1;51(3):313-24.
44. Wallace, R. W.  DNA on a chip - serving up the genome for diagnostics and research. Molecular Medicine Today 1997, 3, 384-389.
45. Covacci, A.; Kennedy, G. C.; Cormack, B.; Rappuoli, R.; Falkow, S. From microbial genomics to meta-genomics. Drug Development Research 1997, 41, 180-192.
46. Forozan, F.; Karhu, R.; Kononen, J.; Kallioniemi, A.; Kallioniemi, O. P. Genome screening by comparative genomic hybridization. Trends in Genetics 1997, 13, 405-409.
47. Sapolsky, Ronald J.;  Winzeler, Elizabeth A. The Functional Analysis Of Genomes: Recent Research In The Laboratory Of Dr. Ronald Davis (at Stanford University)
48. Blanchard, A.P. &  L. Hood.  Sequence to array: probing the genome's secrets. Nature Biotechnology  14:1649, 1996
49. Blanchard, A.P., R.J.Kaiser, L.E.Hood.  High-Density Oligonucleotide Arrays. Biosensors & Bioelectronics 11:687-690, 1996
50. DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM [Stanford and NIH] Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet 1996 Dec;14(4):457-60
51. Shalon D, Smith SJ, Brown PO [Stanford] A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. Genome Res 1996 Jul;6(7):639-45
52. Schena M, Shalon D, Heller R, Chai A, Brown PO, Davis RW [Stanford] Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proc Natl Acad Sci U S A 1996 Oct 1;93(20):10614-9
53. Schena M, Shalon D, Davis RW, Brown PO [Stanford] Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science1995 Oct 20;270(5235):467-70

        See also Andreas Matern's home page on DNA Microarrays.

Academic Links

1. Many academic organizations have set up their mciroarray core facilities in order to make this technology accessible to their reserchers.  Dr. Wentian Li of Rockefeller University maintains a list of such core facilities.
2. DNA Microarray (Genome Chip) homepage (this site, created by Dr. Leming Shi), is a good starting point and contains a lot of useful links and background information. This site was reviewed by Science magazine.
3. Science magazine maintains an excellent collection of information on functional genomics. (www.sciencegenomics.org)
4. Dr. Ruth Alscher (ralscher@vt.edu) at Virginia Tech maintains an excellent Web site GRID IT on DNA Microarrays (http://www.bsi.vt.edu/ralscher/gridit).
5. Gene-Arrays mailing list (maintained by Chandi Griffin at San Francisco General Hospital/UCSF). To subscribe, send a one line e-mail message to listserv@listserv.ucsf.edu; the single line message should be: subscribe Gene-Arrays your-first-name your-last-name. This is a very good place to ask all kinds of questions regarding gene chips and DNA microarrays. To post a question to the whole mailing list, send email to http://www.gene-chips.com/GENE-ARRAYS@ITSSRV1.UCSF.EDU. You may leave the list at any time by sending a "SIGNOFF GENE-ARRAYS" command to listserv@listserv.ucsf.eduFAQ in PDF
6. PlantArrays Mailing List To subscribe send the word "subscribe" to mailto://plantarrays-request@genome.stanford.edu
7. Tim Tranbarger maintains the Plant-Array Website in the context of the WWW Virtual Library ( http://www.w3.org/vl/).
8. A microarrays newsgroup was recently made available at http://www.egroups.com/group/microarray/ (maintained by Philippe Marc).
9. The Association of Biomolecular Resource Facilities (ABRF)'s Microarray Research Group (MARG) conducted a survey on the current status of the microarray technology.  The results is presented in a poster: "THE STATE OF THE ART OF MICROARRAY ANALYSIS: A PROFILE OF MICROARRAY LABORATORIES."
10. The Microarray Site of Nature Genetics
11. Nobel Laureate Martin L. Perl's group at the Stanford Linear Accelerator Center (SLAC) is investigating if their new drop-on-demand inkjet technology originally designed for the searching of certain hypothetical types of elementary particles would be of use in the production of DNA microarrays.
12. Stanford University's Dr. Patrick Brown, one of the major players in this field. This group has a complete guide for researchers to build their own microarrayer, at a fraction of the price of commercial products
13. DNA Microarray Protocols of Dr. Mark Schena: very detailed and useful information on performing DNA microarray experiments.
14. Dr. Mark Schena Home Page
15. NIST ATP Awards 1998: Tools for DNA Diagnostics (7 of the 29 proposals were awarded)  Check project manager Dr. Stanley Abramowitz's overview talk on this field
16. CGAP (Cancer Genome Anatomy Project) at the National Cancer Institute (NCI), NIH.
17. Microarray Project at the National Human Genome Research Institute (NHGRI), NIH
18. The NIEHS cDNA Microarray Center: Human ToxChip v 1.0, Human Discovery Chip, Yeast Chip, Rat Chip, Xenopus Chip v 1.0, and Mouse Chip.
19. Dr. John N. Weinstein at the National Cancer Institute (NCI) developed an "information-intensive" anticancer drug discovery approach that integrates chemical structure information and anticancer activity patterns of >70,000 screened compounds with gene expression (microarray) data of the 60 human cancer cell lines
20. Dr. Alan Robinson's web resource on Gene Expression and Microarray Technologies, at EBI. (highly recommended) links to public sources of expression data, informatics, analysis tools, ...
21. Andreas Matern's home page on DNA Microarrays
22. PhRMA's Microarrays and "DNA chips" site
23. Anatomy of a Comparative Gene Expression Study (by Jeremy Buhle). It's a very nice description of the microarray technology, also includes a Glossary of Microarray-related Biotechnology Terms
24. Whitehead Institute for Biomedical Research/MIT Center for Genome Research
25. Dr. Geoffrey Childs, Functional Genomics at AECOM, Department of Molecular Genetics, Albert Einstein College of Medicine
26. Computational Genomics at Harvard University (Dr. George M. Church, a lot of very useful links)
27. Human Genome Project Information at the Oak Ridge National Laboratory, U.S. Department of Energy
28. National Human Genome Research Institute (NHGRI) is developing "Tissue Chip" to Illuminate the Cancer Development Process. NIH Clinical Study: 97-C-0178: Fludarabine Treatment of Chronic Lymphocytic Leukemia: cDNA Microarray Gene Expression Analysis, and Preclinical Bone Marrow Transplant/Immunotherapy Studies
29. Garner Lab at UTSW - Gene Networks
30. DNA Microarray Technology to identify genes controlling spermatogenesis, Sam Ward at the University of Arizona
31. Vivian Cheung's Lab at The Children's Hospital of Philadelphia focuses on the development of Direct Identical-by-Descent (IBD) Mapping, which is a DNA microarray-based mapping technique that allows isolation and mapping of DNA fragments shared IBD between individuals.
32. University of Washington, Dr. Lee Hood,  Java-based Array Image Spot Finding and Quantification Software (CrazyQuant)
33. Dr. Bernd Weisshaar's listing of DNA microarray links (plants), Max-Planck-Institut für Züchtungsforschung
34. Dr. Landers' Group at the University of Pittsburgh is developing microcolumn technology for clinical diagnostics. This capillary-based Integrated Diagnostic (ID) Chip may have great potential in clinical diagnostics.
35. Dr. Claude Jacq's group at ENS, France. They also maintain a discussion list: pucesadn@ens.fr
36. Toxicogenomics homepage at the Chemical Industry Institute of Toxicology (CIIT): discusses how the DNA microarray technology is impacting toxicological research.
37. Dr. Kent Vrana's Gene Expression Technology Group at the Wake Forest University School of Medicine.
38. The Vanderbilt University Microarray Core Facility (microarrays.com) offers microarray-based products and services.
39. MRC Toxicology Unit DNA Microarray Pages maintained by Dr Timothy W. Gant.
40. The Nylon MicroArrays site provides detailed information on the use of nylon microarrays (allowing expression profiling with small amounts of unamplified RNA) and a number of useful utilities for choosing and checking IMAGE clones representing given genes. contact: jordan@ciml.univ-mrs.fr
41. Arabidopsis Functional Genomics Consortium (AFGC) at Stanford University, funded by NSF: microarrays, knockouts, and plant-specific genes.
42. Dr. Eiichiro Ichiishi of Kyoto Prefectural Univ. of Medicine maintains a Web site on DNA chip technology (in Japanese).
43. Dr. Michael C. Pirrung at Duke University is developing novel methods to cleave DNA strands into the shorter fragments for DNA chip analysis and DNA chip computation.
44. ArrayNL platform©: DNA-chips and microarrays in the Netherlands, maintained at the Department of Human and Clinical Genetics, Leiden University Medical Center.
45. The Microarray Centre at The Ontario Cancer Institute.
46. Links to DNA Microarray protocols , maintained by Longcheng Li at UCSF
47. Biochip Research & Development Center, Tsinghua Univeristy, Beijing, China. Director: Dr. Jing Cheng.
48. Natl. Lab. of Molecular and Biomolecular Elecctronics, Southeast Univ., Nanjing, China.
49. Zicai Liang at Karolinska Institutet.
50. KIChip: Karolinska Institute cDNA Micro-Array Core Facility
51. Dr. Gerhard M. Kreshach maintains a list of more than 1000 links to to Life Science News, Resources & Databases, including DNA, Oligonucleotide, and Protein Arrays
52. Fission yeast functional genomics group at The Sanger Centre headed by Dr. Jurg Bahler.
53. The Xenopus Microarray Project at Rockefeller Univ., includes protocols, software, and links.
54. The U.S. Environmental Protection Agency Microarray Consortium (EPAMAC) (Great!)
55. The Center for Bioelectronics, Biosensors and Biochips at Virgnia Commonwealth University and the Medical Colleage of Virginia Health System focuses on next generation microarrays, integrated molecular electronic devices using biologically active molecules and neurochips.
56. St. George's Hospital Medical School's microarray facility on Bacterial Microarrays.
57. UCLA Human Genetics DNA Microarray Core Facility
58. Cornell Weill Medical College DNA Microarray Core Facility (Dr. Jenny Z. Xiang)
59. Baylor College of Medicine Microarray Core Facility
60. ORNL's Links to the Genetic World
61. Scottish Centre for Genomic Technology and Informatics, Scotland University of Edinburgh.
62. Prof. Andreas Manz of the Imperial College, UK, developed a novel concept for Miniaturized Total Analysis Systems (u-TAS): sampling, any sample pretreatment, separation, and detection steps are all performed in an integrated microsystem.
63. Dr. Michael Weller's group works on protein chips.
64. Prof. Dave Stahl's group at the Univ. of Washington is working on the Phylochip project: developing 16S rRNA-based microchips for determinative, phylogenetic and environmental studies.

Industry Links (Companies are listed alphabetically.)

A good summary of available Human arrays can be found at the September 4, 2000 issue of The Scientist. (by Jorge D. Cortese)

1. ACLARA BioSciences, Inc., (used to be called Soane Biosciences) Hayward, California (Plastic chips and microfluidic systems based on "Lab-On-A-Chip" microfluidics US Patent 5,750,015: "Method and device for moving molecules by the application of a plurality of electrical fields") Wins NIST ATP Award in "Tools for DNA Diagnostics" for Project: Multiplexed Sample Preparation Microsystem for DNA Diagnostics
2. Advanced Array Technology S.A. (Belgium),  BIO-CD™: compact disc platform for DNA detection
3. Affymetrix, Inc., Santa Clara, California (The technology leader; manufactures the widely used GeneChip^®arrays, including HIV, p450, p53, Rat Toxicology U34 arrays, etc.)
4. Agilent Technologies, Inc. (Palo Alto, California), a subsidiary of Hewlett-Packard Company, plans to expand its presence in the life science market through the introduction of a new DNA microarray program. It uses inkjet printing technology to manufacture its oligo-based DNA microarrays. Licensed from Ed Southern/OGT. LabChip™-based DNA and RNA bioanalyzer.
5. Alexion Pharmaceuticals Inc., New Haven, Connecticut
6. Alpha Innotech Corp., San Leandro, CA. Alpha Innotech provides innovation bioinformatic imaging solutions for genetic discovery designed to acquire, manage, and analyze fluorescence, chemiluminescence, or colorimetric microarray slides, plates, gels, blots, or films.
7. AlphaGene, Inc., Woburn, Massachusetts (full length cDNA FLEX™ and MicroFLEX library construction; High Throughput Gene Expression Profiling; High Throughput DNA Sequencing; Bioinformatics)
8. Applied Precision, Inc., Issaquah, Washington. ArrayWoRx is a wide field light source based microarray scanner, combines limitless wavelength possibilities with automation and image processing software.
9. Asper Ltd.,  Estonia. Arrayed Primer Extension (APEX) and Asper ChipReader 003
10. AVIVA Biosciences Corp., San Diego, CA. Dedicated to the application of breakthrough multiple-force biochip technology for genomics and proteomics. The company is developing an integrated sample-to-result AVIChip™ system with an emphasis on biological sample preparation and chip-based molecular manipulation. The AVIChip™ system will separate and transport a variety of mRNA, or other molecules from crude biological samples and simultaneously perform a wide range of biological and biochemical analyses. AVIVA's technology allows fast, accurate, automated, and high-throughput biological analysis on integrated biochip systems and provides novel approaches to both drug development and clinical diagnostics.
11. Axon Instruments, Inc., Foster City, California (GenePix 4000 Integrated Microarray Scanner and Analysis Software, simultaneously scans microarray slides at two wavelengths using a dual laser scanning system, displays images from two wavelengths and a ratio image as they are acquired in real time; US$50,000)
12. AxyS Pharmaceuticals, La Jolla, California: Wins NIST ATP Award in "Tools for DNA Diagnostics" Project: Liquid Array Technology Development
13. Beckman-Coulter
14. Beecher Instruments, Silver Spring, MD. Tissue array technology for high-throughput analysis of tissue specimens.
15. BioArray Solutions, LLC, Piscataway, NJ. Light-controlled Electrokinetic Assembly of Particles near Surfaces (LEAPS), enables  computer controlled assembly of beads and cells into planar arrays within a miniaturized, enclosed fluid compartment on the surface of a semiconductor wafer.
16. BioChip Technologies
17. bioDevice Partners, Cohasset, MA. Provides consulting services to the microarraying community in the area of optics and instrumentation
18. BioDiscovery, Inc., Los Angeles, California (ImaGene™, special image processing and data extraction software; CloneTracker: Databases clones, plates, and slides, and offers array design tool and interfaces to arrayers; GeneSight: Powerful expression analysis software which features statistical methods as well a visualization tools.
19. Biodot
20. Biomedical Photometrics, Inc., (MACROscope™  for reading genetic microarrays, in collaboration with Canadian Genetic Microarray Consortium)
21. bioMerieux, in vitro diagnostics
22. BioRobotics Ltd.,  Comberton, Cambridge, UK (MicroGrid, for arraying oligonucleotides or cDNA clones on glass slides and plastic chips)
23. Brax, Cambridge, UK
24. Cadus Pharmaceutical Corp., Tarrytown, New York (yeast living chip)
25. Caliper Technologies Corp., Palo Alto, California: LabChips™ based on microfluidics. Awarded $2 million contract by NIST to develop high-throughput DNA diagnostic platform. Project: Reference Laboratory LabChip™ DNA Diagnostics System
26. Capital Biochip Corp., Beijing, China. Co-founded on 30th September 2000 by Tsinghua University, Huazhong University of Science and Technology, Chinese Academy of Medical Sciences and Academy of Military Medical Sciences. The registered capital for  Capital Biochip is RMB $390 million with RMB $240 million contributed by the four institutional founding members and RMB $150 million from international venture capital firms. (Note: 1 US dollar = ~8.2 RMB).  It is backed by funds from the Chinese governmental agencies to developed and commercialize various biochip technologies.  It is recruiting qualified researchers from the world.
27. Cartesian Technologies, Inc., Irvine, CA. PixSys PA Series: for Automated liquid handling system for creating high-density arrays for genomics research. Scan Array 3000: A Fluorescent Imaging System for microarray biochips.
28. Celera, Rockville, Maryland (Everyone knows this company!)
29. Cellomics, Inc., Pittsburgh, Pennsylvania (ArrayScan™, cell-based "High Content Screening" (HCS) for drug discovery)
30. Cepheid  Sunnyvale, California (microfluidics)
31. Clinical Micro Sensors, Inc., Pasadena, California. Now part of Motorola. DNA microchip-based medical diagnostics; detection of directly detect DNA via electron transfer. Wins NIST ATP Award in "Tools for DNA Diagnostics" Project: DNA Diagnostics for the Point of Care Using Electronic Nucleic Acid Detection
32. Clondiag Chip Technologies, Jena, Germany. Working on generation and application of DNA microarrays. Current products: Iconoclust (imaging tool), Partisan ArrayLIMS (LIMS for bioarrays).
33. Clontech's Atlas^TM human cDNA array (nylon-membrane based)
34. CombiMatrix Corporation, Burlingame, CA.
35. Compugen's LEADS^TM drug discovery platform for identifying drug targets based on the analysis of EST (Expressed Sequence Tag) and genomic databases, expression results from chips and proteomics, and polymorphism detection and qualification; DNA chip design and analysis. LabOnWeb.com
36. Corning Science Products Division, Acton, MA provides the (Corning Microarray Technology) CMT-GAPS amino silane coated slides and CMT-Hybridization chamber.
37. Corvas International, Inc., (2D gel, proteomics)
38. Cruachem Ltd, U.K. manufactures the phosphoramidite building blocks for the synthesis of DNA. Its expertise in DNA technology provides an efficient service for the supply of DNA oligonucleotides. Cruachem Ltd is enthusiastically looking for partners with which to collaborate in the area of DNA chip technology.
39. CuraGen Corp., New Haven, Connecticut.  GeneCalling™ and Quantitative Expression Analysis (QEA™), CuraMode, CuraTox
40. diaDexus, LLC, Santa Clara, California. joint venture between SmithKline Beecham Corp. and Incyte Pharmaceuticals, Inc.. Specialized in using microarray technology for molecular diagnostics
41. Display Systems Biotech, Inc, Vista, CA and Copenhagen, Denmark. discoveryARRAY slides (over 2400 expressed cDNA fragments); will soon offer over 40,000 arrayed mouse and human genes; GEE-NOME BioInformatic system.
42. DNAmicroarray.com. offers complete "made to order" high density DNA microarray synthesis and analysis services. Prices, availability, and turnaround time seem impressive.
43. Erie Scientific Company, Portsmouth, NH, manufactures microslides for microarrays.
44. Eurogentec, Seraing, Belgium. Sells yeast and Bacillus subtilis genomic membranes.
45. Expression Analysis Inc., RTP, NC., was formed to provide GeneChip processing and gene expression analysis using Affymetrix GeneChip microarrays.
46. Gel biochip
47. First Genetic Trust, Inc., Deerfield, IL. Acting as a third-party intermediary among researchers, health care providers and patients. Its goal is to build a comprehensive, high-security, independent "genetic bank".
48. Gene Logic, Inc., Columbia, Maryland (Flow-thru Chip^TM: has hundreds of thousands of discrete microscopic channels that pass completely through it. Probe molecules are attached to the inner surface of these channels, and target molecules flow through the channels, coming into close proximity to the probes. This proximity facilitates hybridization. READS™, Restriction Enzyme Analysis of Differentially-expressed Sequences, for capturing and analyzing the overall gene expression profile of a given cell or tissue type to identify drug targets).
49. Geneka Biotechnology Inc., Montreal, Canada. Oligonucleotide-based microarray slide, the P.R.O.M. (Proteomic Regulatory Oligonucleotide Microarray). 35-45-mers.
50. Genemachines Genomic Instrumentation Services, Inc., Menlo Park, California (OmniGrid, glass slides or nylon membranes, similar to Dr. Pat Brown's)
51. General Scanning Inc., Watertown, Massachusetts (laser scanning and micropositioning, manufactures MicroArray Biochip Scanning System: ScanArray^TM). Now called GSI Lumonics
52. GeneScreen, Inc.,  The Genetics Profiling Company
53. Genisphere, Oakland, New Jersey. Provides fluorescently-labeled kits for gene expression arrays. (uses highly branched nucleic acids - dendrimer technology)
54. GeneTrace Systems
55. Genetic Analysis Technology Consortium (GATC)
56. Genetic MicroSystems Inc., Woburn, Massachusetts (instrumentation for DNA microarray-based analysis) Acquired by Affymetrix.
57. Genetix Ltd., Christchurch, Dorset, UK (Q-Bot, Q-Pix)

Genicon Sciences Corp, San Diego, CA. Developed an ultra-sensitive signal generation and detection platform technology based on Resonance Light Scattering (RLS) for the simple and efficient detection, measurement and analysis of biological interactions.

58. Genome Systems Inc., St. Louis, MO, a wholly owned subsidiary of Incyte Pharmaceuticals, Inc., GDA: Gene Discovery Array
59. Genometrix Inc., The Woodlands, Texas (Bioscanner™, GeneView®, Universal Arrays™, Risk-Tox)
60. Genomic Solutions, Ann Arbor, Michigan (Flexys™ modular robotic system, GeneTAC™ and Genomic Integrator™ array analysis products automates the imaging and analysis of gene microarrays.)
61. GENPAK Inc, Stony Brook, NY. genpakARRAY 21 robotic microarrayer system and genSTATION 3XL manual microarrayer system.
62. GENSET, Paris, France (specialized in pharmacogenomics)
63. Genemed Synthesis Inc., South San Francisco, CA. Supplies oligos.
64. GenomeWeb,  print and electronic provider of news and information on the business and technology of genomics and bioinformatics worldwide.
65. GeSiM, Germany. The Nano-Plotter is based on piezoelectric pipetting principle.
66. Genzyme Molecular Oncology (SAGE^®: Serial Analysis of Gene Expression)
67. HP GeneArray Scanner (used by Affymetrix and others)
68. Hypromatrix, Inc. , Millbury, MA. Hypromatrix AntibodyArray TM is designed to detect protein-protein interactions, post-translational modification and protein expression.
69. Hyseq Inc., Sunnyvale, California (Sequencing By Hybridization. HyX platform and Gene Discovery, HyGnostics, and HyChip™ modules)
70. Illumina, Inc., San Diego, California. utilizes fiber optics, microfabrication, and advanced information processing to create arrays where 250,000 discrete sensors fit on a probe the diameter of the head of a pin.
71. I.M.A.G.E. Consortium: "Sharing resources to achieve a common goal - the discovery of all genes"
72. Incyte Genomics, Inc., Palo Alto, California (GEM Microarrays, GeneJet^TM array, LifeSeq^® Database with estimated 100,000 genes, and LifeArray Microarray Software)
73. IntegriDerm, Inc., Huntsville, AL. Produces DermArray DNA microarrays for dermatologic research.
74. Intelligent Bio-Instruments, Cambridge, Massachusetts
75. JMAR's Precision Systems, Inc., Chatsworth, CA. Designer and manufacturer of UV exposure and mask aligner systems specifically designed for bio-chip manufacturers. Also produces custom micropositioning systems for micro-spotting equipment and high resolution dimensional metrology and defect inspection systems for quality assurance of bio-chips and DNA microarrays.
76. Lab-on-a-Chip.com, provides focused information on all Lab-on-a-Chip technologies. It includes published papers, news, events, new products, suppliers, research links, jobs and discussion forums.
77. Labman Automation Ltd., North Yorkshire, TS9 5JY, UK (HDMS: Labman High-Density Microarray Spotter)
78. Lifecodes Corp., Stamford, Connecticut (Lifecodes MicroArray System: LMAS)
79. Lynx , Megasort™ is a bead-based process providing differential DNA analysis.
80. Medway SA, Mezzovico, Switzerland. MEDWAY designs, develops, manufactures and commercialises medical devices for diagnostics, robotic systems, optical instruments, fluorescent molecular markers, sieving microchips. Offers GMO testing.
81. Mergen Ltd., San Leandro, CA. ExpressChip™ oligonucleotide microarray. Offers a full range of services.
82. MetriGenix Inc., Gaithersburg, MD. The 4D Array utilizes a patented flow through design that optimizes the surface area to volume ratio, has shorter hybridization times, provides larger binding/signal capacity, and is more readily automated than flat biochips.
83. Micralyne Inc., (formerly Alberta Microelectronic Corp.) Edmonton, Alberta, Canada.  Fabricates micromachined glass, silicon and thin film components for use in microfluidics.
84. MicroFab Technologies, Inc., Plano, TX. manufactures piezoelectric drop-on-demand ink-jet printing technology for

microdispensing fluids.

85. Micronics, Inc., Redmond, Washington. microfluidics based systems for application to clinical laboratory diagnostics: Microcytometer™, H-Filter™, T-Sensor™, and O.R.C.A. µFluidics.
86. Molecular Dynamics, Inc., Sunnyvale, California (Storm® and FluorImager®)
87. Molecular Tool, Inc., Baltimore, Maryland. Genetic Bit Analysis, GBA^®, Genomatic™. Acquired by Orchid Biocomputer on September 14, 1998.
88. Mosaic Technologies, Inc., Waltham, MA. EZ-RAYS^TM activated slide kits for DNA microarrays.
89. Motorola BioChip Systems. Licensed a 3-D gel pad technology from Argonne National Laboratory.
90. Nanolytics is developing Custom Array Synthesis Technology
91. Nanogen, San Diego, California (Electronic Addressing, Concentration, and Hybridization)
92. NEN Life Science Products, Boston, MA (MICROMAX™ Human cDNA Microarray System I for differential gene expression analysis)
93. Oncormed Inc., (acquired by Gene Logic in July, 1998) characterizes genes to establish their clinical relevancy and provides molecular profiling of patients for pharmacogenomic and therapeutic purposes
94. Operon Technologies, Inc., Alameda, CA. Low density (320 or 370 genes, 70-mers) OpArrays^TM microarrays.
95. Orchid BioSciences, Inc., Princeton, New Jersey (a Sarnoff company) microfluidic chips; applying microfabrication processes in glass, silicon, and other materials to create three dimensional structures.  Contained within these devices are small capillary channels less than a millimeter wide. Wins NIST ATP Award in "Tools for DNA Diagnostics" Project: Polymerase Signaling Assay for DNA Variation Detection on Universal Processor Arrays It also has a Web site on single nucleotide polymorphisms (SNPs).
96. OriGene Technologies Inc., Rockville, MD.  Offers SmartArray™  chips (Huamn), including nuclear hormone receptors, homeobox/b-zip/HLH transciption factors, tissue-specific/inducible transcription factors , and phosphotyrosine Kinases.
97. Oxford Gene Technology Ltd (Ed Southern) Oligo-based microarray
98. Packard Instrument Company, Meriden, Connecticut. (BioChip Arrayer)
99. PamGene B.V., The Netherlands. flow-through technology for microarray.
100. PE Applied Biosystems, Wins NIST ATP Award in "Tools for DNA Diagnostics" for project: Integrated, Micro-Sample Preparation System for Genetic Analysis
101. PharmaSeq, Inc., Monmouth Junction (near Princeton), NJ. Developer of microtransponder-based technology for DNA diagnostic assays. Wins NIST ATP Award in "Tools for DNA Diagnostics" for project: Multiplex DNA Diagnostic Assay Based on Microtransponders
102. Phase-1 Molecular Toxicology, Inc., Santa Fe, New Mexico. Molecular and high throughput toxicology using gene chips (Licensed from Xenometrix)
103. Proligo LLC, Boulder, CO.  Nucleic acid supplier.
104. Protogene Laboratories, Palo Alto, California (Surface tension array on glass substrate; "Printing" reagents using drop-on-demand technology)
105. R&D Systems, Minneapolis, M. Cytokine Expression Array allows one to determine the RNA level for approximately 400 cytokines and related factors in one standard hybridization experiment. (charged nylon membrane)
106. Radius Biosciences, Medfield, Massachusetts.  Custom DNA, RNA, PNA, and Protein MicroArray Chips.
107. RELAB AG, Germany, is developing BioChip arrays for diagnostic applications (oncology). The GeneStick platform with arrays on plastic sticks and a new chemiluminescence imager.
108. Research Genetics, Huntsville, Alabama (GeneFilter)
109. RoboDesign International Inc., Carlsbad, CA. Its RoboArrayer is integrated with a vision system to allow for real-time quantification of spot size and spot volume during the printing process.
110. Rosetta Inpharmatics, Kirkland, Washington. FlexJet™ DNA oligonucleotides microarrays (in-situ synthesized on a glass support via ink-jet printing process); Resolver™ Expression Data Analysis System.
111. SciMatrix, Inc., Durham, NC. Offers ArrayWorks^TM, a complete line of custom microarray services, for the production, processing, and analysis of microarrays, using PixSys^TM arrayers from Cartesian Technologies. It also provides customized ArrayEngine^TM microarray systems.
112. Sequana Therapeutics (merged with Arris Pharmaceutical to become AxyS Pharmaceuticals), La Jolla, California
113. Sequenom, Hamburg, Germany, and San Diego, California (DNA MassArray, BiomassPROBE, Biomass SIZE, BiomassSEQUENCE, BiomassSCAN, BiomassINDEX, and SpectroChip)
114. Sigma-Genosys Ltd., The Woodlands, Texas (Panorama™E. coli Gene Arrays, 4,290 genes per array)
115. SuperArray Inc., Bethesda, MD. Their gene expression array (GEArray™ ) systems (Human and mouse) are designed for pathway-specific gene expression profiling.  Also offers ChoiceGEArray to meet customer's specific requirements.
116. SurModics, Inc., Eden Prairie, Minnesota. Manufactures 3D-Link^TM activated slides for the production of microarrays.  Uses amine-modified DNA to hybridize on the surface of the slide.
117. Synteni, Inc., Fremont, California (acquired by Incyte Pharmaceuticals, Inc. in January 1998) (UniGEM™ Gene Expression Microarray)
118. The German Cancer Institute, Heidelberg, Germany
119. TeleChem International, Sunnyvale, California (offers whole system parts: ChipMaker, SmartChips, ArrayIt, Hybridization Cassette, ScanArray 3000, ImaGene Quantification Software, and Super Microarray Substrates)
120. Third Wave Technologies, Inc., Madison, WI. Develops and commercializes simple, low-cost nucleic acid platform technologies to fundamentally alter disease discovery, diagnosis and treatment. Invader^® assay and CFLP^® Technology
121. Tissue Array, for expression study of protein and in situ screening of mRNA.
122. V&P Scientific, Inc., San Diego, CA. Supplies inexpensive replicators ($3000 or so) that will make macroarrays on membranes, or microarrays on slides.
123. Virtek Vision International Inc. (Ontario, Canada) ChipReader™ is a high-sensitivity laser confocal system for rapid imaging of the DNA microarrays.
124. Vysis, Inc., Downers Grove, Illinois (CGH-Comparative Genomic Hybridization; The GenoSensor Microarray System includes genomic microarrays, reagents, instrumentation and analysis software.)
125. Xanthon, Research Triangle Park, North Carolina, has developed a multiplexed, microplate-based electrochemical detection system for high-throughput screening of compounds for their effects on gene expression.  Based on measurement of the oxidation of guanine on an electrode.
126. Xenometrix, Inc., Boulder, CO (Gene Profile Assay and bioinformatics for gene induction profile analysis; a demo is available)
127. XENOPORE Corp., Hawthorne, NJ.  Manufacturer of coated microscope slides, including silanated, silylated, epoxy, streptavidin, nickel chelate, and many other surfaces.

 Table 2. The main features of some hybridization microarray formats currently available*

Company	Product name	Arraying method	Hybridization step	Readout	Main focus
Affymetrix, Inc., Santa Clara, California	GeneChip®	In situ (on-chip) photolithographic synthesis of ~20-25-mer oligos onto silicon wafers, which are diced into 1.25 cm2or 5.25 cm2 chips	10,000-260,000 oligo features probed with labeled 30-40 nucleotide fragments of sample cDNA or antisense RNA	Fluorescence	Expression profiling, polymorphism analysis, and diagnostics
Brax, Cambridge, UK		Short synthetic oligo, synthesized off-chip	1000 oligos on a "universal chip" probed with tagged nucleic acid	Mass spectrometry	Diagnostics, expression profiling, novel gene identification
Gene Logic, Inc., Columbia, Maryland	READSTM
Genometrix Inc., The Woodlands, Texas	Universal Arrays™
GENSET, Paris, France
Hyseq Inc., Sunnyvale, California	HyChip™	500-2000 nt DNA samples printed onto 0.6 cm2 (HyGnostics) or ~18 cm2 (Gene Discovery) membranes      Fabricated 5-mer oligos printed as 1,15 cm2 arrays onto glass (HyChip)	64 sample cDNA spots probed with 8,000 7-mer oligos (HyGnostics) or <=55,000 sample cDNA spots probed with 300 7-mer oligo (Gene Discovery)  Universal 1024 oligo spots probed 10 kb sample cDNAs, labeled 5-mer oligo, and ligase	Radioisotope         Fluorescence	Expression profiling, novel gene identification, and large-scale sequencing (Gene Discovery array), polymorphism analysis and diagnostics (HyGnostics/HyChip arrays), and large-sample sequencing (HyChip array)
Incyte Pharmaceuticals, Inc., Palo Alto, California	GEM	Piezoelectric printing for spotting PCR fragments and on-chip synthesis of oligos	<=1000 (eventually 10,000) oligo/PCR fragment spots probed with labeled RNA	Fluorescence and radioisotope	Expression profiling, polymorphism analysis, and diagnostics
Molecular Dynamics, Inc., Sunnyvale, California	Storm®  FluorImager®	500-5000 nt cDNAs printed by pen onto ~10 cm2 on glass slide	~10,000 cDNA spots probed with 200-400 nt labeled sample cDNAs	Fluorescence	Expression profiling and novel gene identification
Nanogen, San Diego, California	Semiconductor Microchip	Prefabricated ~20-mer oligos, captured onto electroactive spots on silicon wafers, which are diced into <=1 cm2 chips	25, 64, 400 (and eventually 10,000) oligo spots polarized to enhance hybridization to 200-400 nt labeled sample cDNAs	Fluorescence	Diagnostics and short tandem repeat identification
Protogene Laboratories, Palo Alto, California		On-chip synthesis of 40-50-mer oligos onto 9 cm2 glass chip via printing to a surface-tension array	<=8,000 oligo spots probed with 200-400 nt labeled sample nucleic acids	Fluorescence	Expression profiling and polymorphism analysis
Sequenom, Hamburg, Germany, and San Diego, California	MassArray  SpectroChip	Off-set printing of array; around 20-25-mer oligos	250 locations per SpectroChip interrogated by laser desorbtion and mass spectrometry	Mass spectrometry	Novel gene identification, candidate gene validation, diagnostics, and mapping
Synteni, Inc., Fremont, California (acquired by Incyte Pharmaceuticals, Inc.)	UniGEM™	500-5,000 nt cDNAs printed by tip onto ~4 cm2 glass chip	<=10,000 cDNA spots probed with 200-400 nt labeled sample cDNAs	Fluorescence	Expression profiling and novel gene identification
The German Cancer Institute, Heidelberg, Germany		Prototypic PNA macrochip with on-chip synthesis of probes using f-moc or t-moc chemistry	Around 1,000 spots on a 8 x 12 cm chip	Fluorescence/mass spectrometry	Expression profiling and diagnostics

 * to be updated... Modified from Marshall, A.; Hodgson, J.  DNA chips - an array of possibilities. Nature Biotechnology1998, 16(1), 27-31.

Data Mining: Making Sense of Gene Expression Data

Schema of Array Databases and On-line Tools:

1. A comprehensive list of is gene expression database and analysis tools is available at NCGR's GeneX site.
2. Microarray Gene Expression Database (MGED) Group, was formed to facilitate the adoption of standards for DNA-array experiment annotation and data representation, as well as the introduction of standard experimental controls and data normalisation methods.
3. Microarrays databases on the WWW (by Bernard MARTIN and Philippe MARC)
4. NCBI's Gene Expression Omnibus (GEO) public gene expression repository in development - contact Alex Lash - lash@ncbi.nlm.nih.gov
5. ArrayDB (http://genome.nhgri.nih.gov/arraydb/schema.html) at the National Human Genome Research Institute (NHGRI)
6. µArray Center at the National Cancer Institute's is in the final stages of reviewing/implementing a complete, robust schema.
7. expressDB of George Church Lab's at Harvard Medical School: a relational database containing yeast RNA expression data. As of July, 1999 it contains 17.5 million pieces of information loaded from 11 published and in-house expression studies.
8. MAT (Microarray Analysis Tool) at Albert Einstein College of Medicine: based on Java, JDBC, and Sybase SQL.
9. GATC consortium's published schema
10. GeneX: a Collaborative Internet Database and Toolset for Gene Expression Data at the National Center for Genome Resources.
11. GenEx^TM of Silicon Genetics is a public web database that allows scientists to freely distribute and visualize gene expression data (text and image) from microarrays, Affymetrix chips, and related technologies. It can also dynamically generate several graphs from the data being viewed, such as: scatter plots, trees, overlays, ordered lists, line graphs, or physical position graphs. It is designed to store annotations and interpretations on finished experiments, and can access data from SQL databases like GATC or even from flat text files.
12. Stanford MicroArray Database (Oracle)
13. The Arabidopsis Functional Genomics Consortium (AFGC)'s Arabidopsis cDNA Microarray Results
14. ArrayExpress, being developed at the European Bioinformatics Institute, will be a public array-based gene expression data repository. An international meeting on Microarray Gene Expression Databases, November 14-15, 1999.
15. Dr. John Weinstein's Genomics and Bioinformatics Group at the NCI has made some microarray data and tools available online.
16. Michael Eisen
17. Dr. Peter Lemkin at the NCI developed a Java applet, MicroArray Explorer (MAExplorer), which is currently being used in the Mammary Genome Anatomy Program
18. Dr. Leif Peterson's CLUSFAVOR: Partitioning Large-sample Microarray-based Gene Expression Profiles Using Principal Components Analysis
19. SAGEmap: A Public Gene Expression Resource, Alex E. Lash et al., Genome Res. 2000 July 1; 10(7): p. 1051-1060
20. J-Express: Java program for analyzing microarray data. SOM and PCA implemented, by Bjarte Dysvik.
21. MicroArray Informatics at the EBI

 

"House Keeping Genes": http://www.hugeindex.org/;     Khan et al, Cancer Research 58, Nov. 1998, p.5009-5013

Software Providers:

1. Applied Maths, Belgium. GenExplore™ :  2-way cluster analysis, principal component analysis, discriminant analysis, self-organizing maps.
2. BioDiscovery, Inc., Los Angeles, California (ImaGene™, special image processing and data extraction software, powered by MatLab®; GeneSight: hierarchical clustering, artificial neural network (SOM?), principal component analysis, time series; AutoGene™; CloneTracker™)
3. Cose, France. XDotsReader software
4. GeneData AG (Basel, Switzerland), analysis of genomics and proteomics data: GeneData WorkBench, GeneData Expressionist.
5. Gene Network Inference from Large-Scale Gene Expression Data (Patrik D'haeseleer, University of New Mexico).
6. Gene Network Sciences, Ithaca, NY 14850. Accelerates the drug discovery process by creating dynamic computer models of living cells. BioMine for microarray data analysis.
7. Molecular Pattern Recognition web site at MIT's Whitehead Genome Center. Focuses on computational methodologies for the analysis and interpretation of large-scale expression data sets generated by DNA micro-array experiments.
8. Imaging Research, Inc., St. Catharines, Ontario, Canada. The company writes software, develops detection technologies, and integrates systems for image analysis. Its PC-based ArrayVision^TMsystem has been widely used for rapid and automated analysis of genome arrays.
9. LION Bioscience AG's arraySCOUT™is a new software for analyzing gene expression data. arraySCOUT™ is able to link all expression data to internal and external biological databases via SRS. This link provides information on the function, structure and metabolic pathways of genes from up to 400 databases. arrayTAG - cDNA collections specifically tailored to chip technology; arrayBASE - cDNA annotations in a comprehensive database.
10. Molecular Applications Group, Palo Alto, CA. Stingray™ is integrated software and database products for gene expression, gene function, and gene sequence analysis from microarray data. It is integrated with and dependent upon the use of Affymetrix's  GeneChip^® system and its Expression Data Mining Tool (EDMT) software. [Its ownership of and rights to Stingray™ were sold to Affymetrix in December, 1999.] No longer a corporate entity.
11. MolecularWare, Inc.: ArrayAnalyzerDB
12. Partek, Inc., St. Peters, Missouri. Provider of pattern recognition and data visualization software for science and engineering. Its Partek Pro 2000 system has been used by companies to analyze microarray gene expression data.
13. Rosetta Inpharmatics, Kirkland, Washington. Resolver™ Expression Data Analysis System.
14. Scanalytics, Inc. , Fairfax, VA. Its MicroArray Suite enables researchers to acquire, visualize, process, and analyze gene expression microarray data. Developed by scientists at the NIH's National Human Genome Research Institute.
15. Silicon Genetics' GeneSpring^TM workbench for analyzing experiments based upon genomic expression experiments.
16. Spotfire, Inc., Cambridge, Massachusetts. Offers advanced data visualization capabilities including the ability to perform gene cluster analysis and metabolic pathway mapping. The Spotfire Array Explorer is particularly attractive to experimentalists performing microarray analysis.
17. Media Cybernetics, L.P., Silver Spring, MD: Array-Pro(R).
18. Microarray Software developed by Stanford University
19. Synomics Ltd., Cambridge, UK  (bioinformatics)
20. TIGR (The Institute for Genome Research) offers software tools (free for academic institutions) for array analysis.
21. Dr. Terry Speed's Microarray Data Analysis Group Page: very good resource on statistics aspects of microarray data [Berkeley]
22. GCG's SeqArray Improves MicroArray Data Analysis, Visualization, and Management
23. PREMIER Biosoft International, Palo Alto, CA. Array Designer - designs PCR primers and oligonucleotide probes for microarrays
24. OmniViz, Inc., Columbus, OH, a subsidiary of Battelle.  Provides information visualization and data mining solutions for life and chemical sciences.  Product: OmniViz Pro
25. ViaLogy Corp., utilizes quantum interferometric computing to analyze biochips
26. Xpogen Inc., Cambridge, MA. Web-based tools for organizing, sharing, analyzing, and interpreting gene expression microarray data and associated annotation. "relevance networks".

Articles on Microarray Datamining:

Wentian Li of  Rockefeller University maintains a list of papers on data analysis: http://linkage.rockefeller.edu/wli/microarray/

On-line Information

The International Society for Computational Biology (ISCB).

Plaid models for microarrays and DNA expression at Stanford University

Patrik D'haeseleer [University of New Mexico]: Gene Network Inference from Large-Scale Gene Expression  good discussions and a list of articles. [with Incyte, NIH]

Michael P. S. Brown, William Noble Grundy, David Lin, Nello Cristianini, Charles Sugnet, Terrence S. Furey, Manuel Ares, Jr., David Haussler [UCSC]. Knowledge-based Analysis of Microarray Gene Expression Data Using Support Vector Machines. (SVMs are considered a supervised computer learning method.)

Pacific Symposium on Biocomputing 2000
Pacific Symposium on Biocomputing 1999

The Nature of GED (Gene Expression data); Experimental Variables (Dimensionality); Quality (Reproducibility) of GED; Extracting Signal from Noise; Statistical Approach; Artificial Intelligence-Based Approach; Interpretation of Results; Publicly Available GED (GEO, EBI, SAGE, ...)

Protein Chips (Protein Arrays)

The idea of protein microarray is not new.  In fact, the basics and theoretical considerations of protein microarrays were done in the 1980's by Roger Ekins and coleagues. See, e.g., Ekins R.P., J Pharm Biomed Anal 1989. 7: 155; Ekins R.P. and Chu F.W., Clin Chem 1991. 37: 1955; Ekins R.P. and Chu F.W, Trends in Biotechnology, 1999, 17, 217-218.

The are two main objectives for proteomic research: 1. quantification of all the proteins expressed in a cell; 2. functional study of thousands of proteins in parallel.  For quantification purpose, the standard method is 2D gel separation followed by MS identification.  For protein function study, microarray-based assays are being used to study protein-protein and protein-ligand interations.

News: Gavin MacBeath and Stuart L. Schreiber of Harvard University just published a paper on protein microarray - more than 10,000 protein spots were printed on a glass slide.  The chip was used to identify protein-protein and protein-drug interactions.  I believe it's a truly breakthrough for proteomics and for drug discovery.  G. MacBeath and S.L. Schreiber, Printing Proteins as Microarrays for High-Throughput Function Determination, Science 2000 September 8; 289(5485): p. 1760-1763. Abstract   The question is how to get thousands of pure proteins and keep them in their natural conformation.

Articles

1. BioInsights recently finished a strategic report on protein chips: sales of protein chips are likely to balloon from $45 million in 2000 to almost $500 million in 2006. Press release.
2. MacBeath G. and Schreiber SL, Printing Proteins as Microarrays for High-Throughput Function Determination, Science 2000 September 8; 289(5485): p. 1760-1763. Abstract
3. de Wildt RM, Mundy CR, Gorick BD, Tomlinson IM. Antibody arrays for high-throughput screening of antibody-antigen interactions. Nat Biotechnol. 2000 Sep;18(9):989-994
4. Irving RA, Hudson PJ. Proteins emerge from disarray. Nat Biotechnol., 2000 Sep;18(9):932-933.
5. Aled M. Edwards, Cheryl H. Arrowsmith, and Bertrand des Pallieres, Proteomics: New tools for a new era, Modern Drug Discovery, 2000, Sept., 3(7) 34-44.
6. Kollol Pal, The Keys to chemical genomics, Modern Drug Discovery, 2000, Sept., 3(7) 46-55.
7. Joos TO, Schrenk M, Hopfl P, Kroger K, Chowdhury U, Stoll D, Schorner D, Durr M, Herick K, Rupp S, Sohn K, Hammerle H, A microarray enzyme-linked immunosorbent assay for autoimmune diagnostics. Electrophoresis, 2000 Jul;21(13):2641-50 [Mdeline]
8. Walter G, Bussow K, Cahill D, Lueking A, Lehrach H., Protein arrays for gene expression and molecular interaction screening, Curr Opin Microbiol. 2000 Jun;3(3):298-302.
9. Arenkov P.;Kukhtin A.;Gemmell A.;Voloshchuk S.;Chupeeva V.;Mirzabekov A., Protein Microchips: Use for Immunoassay and Enzymatic Reactions, Analytical Biochemistry, 2000, 278, 2, 123-131
10. Emili AQ and Cagney G. Large-scale functional analysis using peptide or protein arrays. Nat Biotechnol. 2000 Apr;18(4):393-7. Review. [Medline]
11. Ge H., UPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactions. Nucleic Acids Res. 2000 Jan 15;28(2):e3
12. Lueking A, Horn M, Eickhoff H, Bussow K, Lehrach H, Walter G [Max Planck] Protein microarrays for gene expression and antibody screening. Anal. Biochem. 1999 May 15;270(1):103-111
13. Zong Q, Schummer M, Hood L, Morris DR. Messenger RNA translation state: the second dimension of high-throughput expression screening. Proc Natl Acad Sci U S A 1999 Sep 14;96(19):10632-6.
14. Mendoza LG, McQuary P, Mongan A, Gangadharan R, Brignac S, Eggers M. [Genometrix] High-throughput microarray-based enzyme-linked immunosorbent assay (ELISA). Biotechniques 1999 Oct;27(4):778-80, 782-6, 788. [Medline]
15. Brett D. Martin,* Bruce P. Gaber, Charles H. Patterson, and David C. Turner,  Direct Protein Microarray Fabrication Using a Hydrogel "Stamper", Langmuir, 14 (15), 3971 -3975, 1998.

Related sites

• Dr. Konrad Büssow at Max-Planck-Institut für Molekulare Genetik
• Large Scale Proteomics Corporation, Rockville, MD, a subsidiary of Large Scale Biology Corporation.
• Ciphergen Biosystems, Palo Alto, California. ProteinChip™ Arrays for the investigation of proteins on the femtomole scale directly from their "native" environments. Based on Surface-Enhanced Laser Desorption/Ionization (SELDI™).
• NMI (Natural and Medical Sciences Institute), a protein array for autoimmune diagnostics.
• Proteome, Inc.
• Proteome Systems Ltd.,
• SenseTherapeutic Ltd., Cambridge, UK. COVET™ protein microarrays (Cloned Open reading frames for the Validation of Experimental Targets).
• ExPASy (Expert Protein Analysis System) proteomics server of the Swiss Institute of Bioinformatics (SIB).
• GeneBio (Geneva Bioinformatics S.A.)
• LumiCytes, Inc., Fremont, CA. SELDI BioChip based molecular profiling platform.
• Cambridge Healthtech Institute's conference on Human Proteome Project, April 2-4, 2001, McLean, VA.

Chemical Microarrays

1. Graffinity Pharmaceutical Design GmbH, Heidelberg, Germany. Uses chemical microarrays as screening tools to enhance the understanding of protein binding specificity, based on diversity Label-free Detection
2. Gregory A. Korbel, Gojko Lalic, and Matthew D. Shair*; Reaction Microarrays: A Method for Rapidly Determining the Enantiomeric Excess of Thousands of Samples, Journal of the American Chemical  Society; 2001; 123(2); 361-362.
3. Eric LeProust et al., Digital Light-Directed Synthesis. A Microarray Platform That Permits Rapid Reaction Optimization on a Combinatorial Basis, J. Comb. Chem., 2 (4), 349 -354, 2000.
4. Paul J. Hergenrother, Kristopher M. Depew, and Stuart L. Schreiber*; Small-Molecule Microarrays: Covalent Attachment and Screening of Alcohol-Containing Small Molecules on Glass Slides, Journal of the American Chemical Society; 2000; 122(32); 7849-7850
5. Gavin MacBeath, Angela N. Koehler, and Stuart L. Schreiber*; Printing Small Molecules as Microarrays and Detecting Protein-Ligand Interactions en Masse, Journal of the American Chemical Society; 1999;121(34); 7967-7968

Related Meetings / Workshops

Please suggest new links to be listed here.

• Genome and Biotechnology Meeting Calendar at DOE's Oak Ridge National Laboratory
• IBC's Emerging Microarray Technologies and Applications, March 18-22, 2002, San Diego, CA,

You missed:

• IBC 8th Annual Biochip Technologies Conference - Chips To Hits, October 29 - November 1, 2001, San Diego, CA.
• smallTalk 2001: The Microfluidics, Microarrays, and BioMEMS Conference and Exhibition, August 27-31, 2001, San Diego, California, USA. Sponsored by the Association for Laboratory Automation.
• IBC's 6th Annual Drug Discovery Technology 2001, August 13-17, 2001, Boston, MA, USA
• EuroBiochips: Microarray and Microfluidic Technology Congress, June 5-8, 2001, Hilton Munich Park, Munich, Germany. (IBC)
• 2001 Northwest Microarray Conference, Seattle WA.
• ABRF Microarray Survey: 2000-2001. An analysis of data submitted to this survey will be presented at the ABRF2001 meeting in February 2001
• Bioinformatics Strategies for Application of Genomic Tools to Environmental Health Research, March 5, 2001, National Center for Toxicogenomics (NCT), Raleigh, NC, USA.  Accompanying symposium at NCSU.
• BIOCHIPS 2001 - Technology Development & Application, March 12 - 13, 2001, Brooklyn, New York, USA.
• Protein Microarray Technology, March 21-23, 2001 - San Diego, CA. (IBC). Keynote speaker: Prof. Roger Ekins
• 3rd MGED: The Third International Meeting on Microarray Data Standards, Annotations, Ontologies and Databases, March 29-31, 2001, Stanford University, CA, USA.
• Cambridge Healthtech Institute's conference on Human Proteome Project, April 2-4, 2001, McLean, VA.
• Chemo*Bio Informatics, February 15-16, 2001 - Sheraton San Diego Hotel & Marina, San Diego, CA. (IBC)
• Cambridge Healthtech Institute's Third Annual Integrated Bioinformatics - High-Throughput Interpretation of Pathways and Biology, January 24-26, 2001, Zurich, Switzerland.
• Cambridge Healthtech Institute's Third Annual Lab-on-a-Chip and Microarrays for Biomedical and Biotechnical Applications, January 22-24, 2001, Zurich, Switzerland.
• CAMDA'00 Conference: Critical Assessment of Techniques for Microarray Data Mining, December 18-19, 2000, Duke University, Durham, NC,
• IBC’s 7th Annual Biochip Technologies Conference - Chips To Hits, November 6-9, 2000, Philadelphia, PA.
• IBC's Biomics Congress, November 13-16, 2000, Stuttgart, Germany.
• '2000 International Forum on Biochip Technologies, October 11-14, 2000, Beijing, China.
• The Northwest MicroArray Conference,  September 6-8, 2000, The University of Washington, Seattle, WA.
• Duke Workshop: Functional Genomics and Microarray Data Mining, Aug 3-4, 2000, Duke University, Durham, NC.
• CHI's High Throughput Technologies, June 19-21, 2000, Philadelphia, PA.
• The Second International Meeting on Microarray Data Standards, Annotations, Ontologies and Databases, May 25 - 27, 2000, Heidelberg, Germany.
• smallTalk2000: The Microfluidics and Microarrays Conference, July 8-12, 2000, Hyatt Regency Hotel, San Diego, California, USA. Sponsored by the Association for Laboratory Automation.
• Cambridge Healthtech Institute's first annual Lab-Chips and Microarrays Japan, May 8-9, 2000, Tokyo, Japan.
• Cambridge Healthtech Institute's first annual MACRO RESULTS FROM MICROARRAYS: Establishing Leads for Drug Development, April 3-5, 2000, Cambridge, Massachusetts.
• Genetix Ltd’s International Microarray Users Forum, November 16-18 1999, Burley Manor Hotel, Burley, Hants. UK.
• 7th Conference on Small Genomes, November 14-17, 1999, The Doubletree Hotel, Arlington, Virginia. Sponsored by the U. S. Department of Energy, The Office of Naval Research, and the National Science Foundation. There are some talks on DNA microarrays.
• Microarray Algorithms and Statistical Analysis: Methods and Standards, November 9-12, 1999, Granlibakken at Lake Tahoe, California. This conference will be totally focused on the internals and methods of the mathematical and algorithmic side of sequencing and microarray analysis. It is not a forum for the presentation of new scientific data of a biological nature that is being generated using sequencing or arrays.
• IBC's 6th Annual Biochip Technologies Conference: Chips to Hits '99, November 2-5, 1999, Berkeley, California. This event will certainly be another big success.
• There is a Microarray Technology Workshop being held at George Mason University (IB3, The Institute for Biosciences, Bioinformatics and Biotechnology) at George Mason University on October 12-15, 1999.
• The Microarray Meeting--Technology, Application and Analysis, September 22 - 25, 1999, Mountain Shadows Marriott Resort Scottsdale, Arizona. Confirmed speakers include most major players in this field. call BioEdge.Net (phone: US: +1-800-737-1333; International: +1-402- 996-9185) for information on submitting abstracts.
• Association of Biomolecular Resource Facilities 1999 Meeting: Bioinformatics and Biomolecular Technologies: Linking Genomes, Proteomes and Biochemistry
• Lab Chips and Microarrays for Biotechnical Applications, January 1999  Zurich, Switzerland
• Stanford Bioinformatics Symposium
• IBC's Fifth Annual Conference on  Biochip Technologies
• IBC's conference on Molecular Toxicology , April 29-30, 1999, The Watergate Hotel, Washington, D.C. (many talks on DNA microarrays)
• FDA seminar on microarray technology (July, 1998) (Not accessible from outside of the fda.gov domain)

Stocks

In addition to the numerous inqueries I received on the technical part of DNA microarray I also received many requests from my visitors for investment advices. Unfortunately, I am not a financial adviser. However, I list here some of the stocks that are related to the DNA microarracy technology in one way or another. Warning: This is FYI only and I shall not be held responsible for your investment outcome. If you think this site helped you make a good investment decision you are welcome to make a donation to maintain it and/or send my little kids some Pokemon toys :)-  Good luck!

View All Stocks

Others

• Motorola, Packard Instrument Co., and Argonne National Laboratory to Develop Advanced Biochip Technology
• From DNA Chips to Potato Chips....
• Welcome to BioTech
• Resources at NCBI: BLAST, dbEST, Entrez, GenBank, MMDB, PubMed
• The Genome Database (GDB)
• GeneCards is a database of human genes, their products and their involvement in diseases. It offers concise information about the functions of all human genes that have an approved symbol, as well as selected others. It is especially useful for those who are searching for information about large sets of genes or proteins, e.g. for scientists working in functional genomics and proteomics.
• Myriad's Yeast two-hybrid system pathways

Shoko Kawamoto, Tadashi Ohnishi, Hiroko Kita, Osamu Chisaka, and Kousaku Okubo [Osaka/Kyoto]. Expression Profiling by iAFLP: A PCR-Based Method for Genome-Wide Gene Expression Profiling. Genome Res 1999 Dec;9(12):1305-1312

Wheeler DL, Chappey C, Lash AE, Leipe DD, Madden TL, Schuler GD, Tatusova TA, Rapp BA. Database resources of the National Center for Biotechnology Information, Nucleic Acids Res. 2000 Jan 1;28(1):10-4.

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