**The Third**

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**MicroArray Quality Control**

**Project Meeting**

December 1-2, 2005

Palo Alto, California

<http://edkb.fda.gov/MAQC/>

> *Co-sponsored by:*
>
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>
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> **Contents of the Meeting Handout:**

1.  Meeting Agenda

2.  Introduction to the MAQC Project

    -   Overview

    -   Implementation and progress

    -   Participating organizations

    -   Publication plan

    -   Timeline

3.  List of Registered Meeting Participants

**Notes:**

1.  The results to be presented at the MAQC project meeting should be
    considered preliminary and do not necessarily represent the final
    conclusions of the MAQC project.

2.  The main objectives of the MAQC project meeting are:

    -   To allow participants an opportunity to review the datasets,
        exchange ideas about data analysis and QC metrics/thresholds
        based on the preliminary analysis results;

    -   To decide on the next phase of the MAQC project (rat or mouse);

    -   To discuss the proposed publication plan and to decide
        additional analyses that need to be performed for each
        manuscript.

3.  The entire MAQC project meeting (including discussion sessions) will
    be recorded.

4.  Information presented at the MAQC meeting should be considered
    confidential and should not be distributed beyond participants of
    the MAQC meeting.

**The MAQC Project Meeting Agenda**

December 1-2, 2005, Cyprus Room, Crowne Plaza Cabana, Palo Alto, CA

+---------+-------------------------------+---------------------------+
| **[Day  |                               |                           |
| One:    |                               |                           |
| Th      |                               |                           |
| ursday, |                               |                           |
| D       |                               |                           |
| ecember |                               |                           |
| 1,      |                               |                           |
| 2005]{. |                               |                           |
| mark}** |                               |                           |
|         |                               |                           |
| Chair:  |                               |                           |
| Yvonne  |                               |                           |
| Dragan  |                               |                           |
| (FD     |                               |                           |
| A/NCTR) |                               |                           |
+---------+-------------------------------+---------------------------+
| 8:00 am | Chair's remarks               | Yvonne Dragan             |
+---------+-------------------------------+---------------------------+
| 8:05 am | Welcome                       | Ronald Davis (Stanford)   |
+---------+-------------------------------+---------------------------+
| 8:10 am | Overview of the MAQC project  | Leming Shi (FDA/NCTR)     |
+---------+-------------------------------+---------------------------+
| 8:20 am | MAQC reference RNA samples    | James Fuscoe (FDA/NCTR)   |
+---------+-------------------------------+---------------------------+
| **Seven |                               |                           |
| Mic     |                               |                           |
| roarray |                               |                           |
| P       |                               |                           |
| latform |                               |                           |
| s[\*]{. |                               |                           |
| mark}** |                               |                           |
| Co-     |                               |                           |
| chairs: |                               |                           |
| Mike    |                               |                           |
| Wilson  |                               |                           |
| (Am     |                               |                           |
| bion)/F |                               |                           |
| ederico |                               |                           |
| G       |                               |                           |
| oodsaid |                               |                           |
| (CDER)  |                               |                           |
+---------+-------------------------------+---------------------------+
| 8:30 am | Inter-site reproducibility    | Xu Guo (Affymetrix)       |
+---------+-------------------------------+---------------------------+
| 8:45 am | Cross-site performance of     | Jim Collins (Agilent)     |
|         | one- and two-color platforms  |                           |
+---------+-------------------------------+---------------------------+
| 9:00 am | ABI expression array data     | Yongming Sun (Applied     |
|         | comparison                    | Biosystems)               |
+---------+-------------------------------+---------------------------+
| 9:15 am | DualChip platform: concept    | Francoise de Longueville  |
|         |                               | (Eppendorf)               |
+---------+-------------------------------+---------------------------+
| 9:30 am | GEH:                          | Richard Shippy (GE        |
|         |                               | Healthcare)               |
+---------+-------------------------------+---------------------------+
| 9:45 am | Performance metrics for       | Eugene Chudin (Illumina)  |
|         | cross-platform studies        |                           |
+---------+-------------------------------+---------------------------+
| 10:00   | Analysis of NCI home brew     | Ernest Kawasaki (NCI)     |
| am      | 70mer arrays                  |                           |
+---------+-------------------------------+---------------------------+
| 10:15   | **Break**                     |                           |
| am      |                               |                           |
+---------+-------------------------------+---------------------------+
| **Three |                               |                           |
| Alte    |                               |                           |
| rnative |                               |                           |
| Tec     |                               |                           |
| hnology |                               |                           |
| P       |                               |                           |
| latform |                               |                           |
| s[\*]{. |                               |                           |
| mark}** |                               |                           |
| Co-     |                               |                           |
| chairs: |                               |                           |
| F       |                               |                           |
| ederico |                               |                           |
| Goodsa  |                               |                           |
| id/Mike |                               |                           |
| Wilson  |                               |                           |
+---------+-------------------------------+---------------------------+
| 10:30   | TaqMan^®^ gene expression     | Kathy Lee (Applied        |
| am      | assays for microarray         | Biosystems)               |
|         | validation                    |                           |
+---------+-------------------------------+---------------------------+
| 10:45   | Cross-platform comparison     | Yuling Luo (Genospectra)  |
| am      | based on 245 genes            |                           |
+---------+-------------------------------+---------------------------+
| 11:00   | Numerical calibration of 205  | James Willey (Gene        |
| am      | genes                         | Express)                  |
+---------+-------------------------------+---------------------------+
| 11:15   | 1.  Quality of data from your | **Panel**: Shawn Baker,   |
| am      |     test sites                | Jim Collins, Francoise de |
| **Discu |                               | Longueville, Xu Guo,      |
| ssion** | 2.  Lessons learned:          | Ernest Kawasaki, Kathy    |
| (10     |     challenges & pitfalls     | Lee, Yuling Luo, Richard  |
| p       |                               | Shippy, Yongming Sun,     |
| latform | 3.  Cost (\$ & time) and      | James Willey              |
| pro     |     value to your org.        |                           |
| viders) |                               |                           |
|         | 4.  Suggestions for the MAQC  |                           |
|         |     project                   |                           |
|         |                               |                           |
|         | 5.  Comments from external    |                           |
|         |     test sites                |                           |
+---------+-------------------------------+---------------------------+
| 12:00   | **Lunch** (on your own)       |                           |
| pm      |                               |                           |
+---------+-------------------------------+---------------------------+
| **Ten   |                               |                           |
| Data    |                               |                           |
| A       |                               |                           |
| nalysis |                               |                           |
| Sites   |                               |                           |
| (I      |                               |                           |
| )[\*]{. |                               |                           |
| mark}** |                               |                           |
| Co-     |                               |                           |
| chairs: |                               |                           |
| R       |                               |                           |
| oderick |                               |                           |
| Jensen  |                               |                           |
| (UM     |                               |                           |
| B)/Marc |                               |                           |
| Salit   |                               |                           |
| (NIST)  |                               |                           |
+---------+-------------------------------+---------------------------+
| 1:15 pm | Intra-platform,               | Walter Liggett (NIST)     |
|         | inter-laboratory variation    |                           |
+---------+-------------------------------+---------------------------+
| 1:30 pm | Correlation estimation from a | Sheng Zhong (UIUC)        |
|         | random effects model          |                           |
+---------+-------------------------------+---------------------------+
| 1:45 pm | Assessing consistency of the  | Wenjun Bao/Tzu-Ming Chu   |
|         | MAQC platforms                | (SAS)                     |
+---------+-------------------------------+---------------------------+
| 2:00 pm | Repeatability,                | Wendell Jones (Expr.      |
|         | reproducibility, and          | Analysis)                 |
|         | inter-platform consistency    |                           |
+---------+-------------------------------+---------------------------+
| 2:15 pm | Integrating the MAQC project  | Hanlee Ji (Stanford)      |
|         | into clinical diagnostic      |                           |
|         | applications: Lessons from    |                           |
|         | the clinical laboratories     |                           |
+---------+-------------------------------+---------------------------+
| 2:30 pm | QRI image analysis of         | Cecilie Boysen (ViaLogy)  |
|         | Affymetrix GeneChip .DAT      |                           |
|         | files                         |                           |
+---------+-------------------------------+---------------------------+
| 2:45 pm | An extensive survey of        | *Lisa Croner (Biogen      |
|         | analysis methods              | Idec)*                    |
+---------+-------------------------------+---------------------------+
| 3:00 pm | QC metrics/thresholds &       | Leming Shi/Weida Tong     |
|         | analysis methods              | (FDA/NCTR)                |
+---------+-------------------------------+---------------------------+
| 3:15 pm | **Break**                     |                           |
+---------+-------------------------------+---------------------------+
| **Ten   |                               |                           |
| Data    |                               |                           |
| A       |                               |                           |
| nalysis |                               |                           |
| Sites   |                               |                           |
| (II     |                               |                           |
| )[\*]{. |                               |                           |
| mark}** |                               |                           |
| Co-     |                               |                           |
| chairs: |                               |                           |
| Marc    |                               |                           |
| Salit/R |                               |                           |
| oderick |                               |                           |
| Jensen/ |                               |                           |
+---------+-------------------------------+---------------------------+
| 3:30 pm | Cross-platform probe mapping  | Roderick Jensen (UMB)     |
|         | and quality metrics for the   |                           |
|         | 1000 chosen genes             |                           |
+---------+-------------------------------+---------------------------+
| 3:45 pm | Mapping probes to RefSeq      | Damir Herman (NCBI)       |
|         | transcripts                   |                           |
+---------+-------------------------------+---------------------------+
| 4:00 pm | Probe design and alternative  | *Jean Thierry-Mieg        |
|         | splicing on data consistency  | (NCBI)*                   |
+---------+-------------------------------+---------------------------+
| 4:15 pm | 1.  Probe-target mapping &    | **Panel**: Wenjun Bao,    |
| **Discu |     master indices            | Cecilie Boysen, Lisa      |
| ssion** |                               | Croner, Damir Herman,     |
| (10     | 2.  Performance metrics and   | Walter Liggett, Roderick  |
| a       |     thresholds                | Jensen, Hanlee Ji, Wendel |
| nalysis |                               | Jones, Jean Thierry-Mieg, |
| sites)  | 3.  Normalization & gene      | Weida Tong, Chunlin Xiao, |
|         |     selection methods         | Sheng Zhong               |
|         |                               |                           |
|         | 4.  Flagged spots and outlier |                           |
|         |     arrays                    |                           |
|         |                               |                           |
|         | 5.  Future directions of data |                           |
|         |     analysis                  |                           |
|         |                               |                           |
|         | 6.  Biogen Idec's request for |                           |
|         |     data access               |                           |
+---------+-------------------------------+---------------------------+
| 5:00 pm | Adjourn                       |                           |
+---------+-------------------------------+---------------------------+

[\*Each speaker has 10 minutes for presentation and 5 minutes for
questions/discussion.]{.mark}

+---------+------------------------------------+-----------------------+
| **[Day  |                                    |                       |
| Two:    |                                    |                       |
| Friday, |                                    |                       |
| D       |                                    |                       |
| ecember |                                    |                       |
| 2,      |                                    |                       |
| 2005]{. |                                    |                       |
| mark}** |                                    |                       |
|         |                                    |                       |
| Chair:  |                                    |                       |
| William |                                    |                       |
| S       |                                    |                       |
| likker, |                                    |                       |
| Jr.     |                                    |                       |
| (FD     |                                    |                       |
| A/NCTR) |                                    |                       |
+---------+------------------------------------+-----------------------+
| 8:00 am | Chair's remarks                    | William Slikker, Jr.  |
+---------+------------------------------------+-----------------------+
| 8:10 am | **Keynote address**: Data quality  | Ronald Davis          |
|         | in genomics                        |                       |
+---------+------------------------------------+-----------------------+
| **      |                                    |                       |
| Invited |                                    |                       |
| P       |                                    |                       |
| resenta |                                    |                       |
| tions** |                                    |                       |
| Chair:  |                                    |                       |
| William |                                    |                       |
| S       |                                    |                       |
| likker, |                                    |                       |
| Jr.     |                                    |                       |
+---------+------------------------------------+-----------------------+
| 8:50 am | ERCC: The External RNA Controls    | Janet Warrington      |
|         | Consortium                         | (Affymetrix)          |
+---------+------------------------------------+-----------------------+
| 9:00 am | The Metrology for Gene Expression  | Marc Salit (NIST)     |
|         | Program                            |                       |
+---------+------------------------------------+-----------------------+
| 9:10 am | Array standardization and the MfB  | Carole Foy (LGC, UK)  |
|         | Programme                          |                       |
+---------+------------------------------------+-----------------------+
| 9:20 am | Rat reference RNAs for proficiency | Karol Thompson        |
|         | testing                            | (FDA/CDER)            |
+---------+------------------------------------+-----------------------+
| 9:30 am | Study design and analysis of       | Winston Kuo (Harvard) |
|         | multiple platforms (mouse)         |                       |
+---------+------------------------------------+-----------------------+
| 9:40 am | Proficiency testing using MTRRM    | Laura Reid (Expr.     |
|         | and MAQC samples                   | Analysis)             |
+---------+------------------------------------+-----------------------+
| 9:50 am | 10^th^ Anniversary of *Science*    | Mark Schena (TeleChem |
|         | 95' paper                          | ArrayIt)              |
+---------+------------------------------------+-----------------------+
| 10:00   | MAQC rat mini pilot project:       | Hongzhu Ren (EPA)     |
| am      | preliminary data                   |                       |
+---------+------------------------------------+-----------------------+
| 10:05   | Preliminary results using rat RNA  | James Fuscoe (FDA)    |
| am      | samples                            |                       |
+---------+------------------------------------+-----------------------+
| 10:10   | **MAQC for rat and/or mouse?**     | Federico Goodsaid     |
| am      |                                    |                       |
|         | 1.  Survey of interest: platform   |                       |
|         |     providers, test sites          |                       |
|         |                                    |                       |
|         | 2.  RNA samples                    |                       |
|         |                                    |                       |
|         | 3.  Experimental design            |                       |
|         |                                    |                       |
|         | 4.  Timeline                       |                       |
+---------+------------------------------------+-----------------------+
| 10:30   | **Break**                          |                       |
| am      |                                    |                       |
+---------+------------------------------------+-----------------------+
| **Reg   |                                    |                       |
| ulatory |                                    |                       |
| P       |                                    |                       |
| erspect |                                    |                       |
| ives:** |                                    |                       |
| Co-     |                                    |                       |
| chairs: |                                    |                       |
| Yvonne  |                                    |                       |
| D       |                                    |                       |
| ragan/F |                                    |                       |
| ederico |                                    |                       |
| G       |                                    |                       |
| oodsaid |                                    |                       |
+---------+------------------------------------+-----------------------+
| 10:45   | Hybridization standards for        | Federico Goodsaid     |
| am      | regulatory review                  |                       |
+---------+------------------------------------+-----------------------+
| 10:55   | 1.  Expected uses of the MAQC      | **Panel**:            |
| am      |     datasets                       |                       |
|         |                                    | Yvonne Dragan,        |
|         | 2.  Proficiency tests              | Federico Goodsaid,    |
|         |                                    | Francis Kalush, Scott |
|         | 3.  External spike-in controls     | Pine, Hongzhu Ren,    |
|         |                                    | Weida Tong            |
|         | 4.  Remaining challenges (prior to |                       |
|         |     RNA)                           |                       |
|         |                                    |                       |
|         | 5.  Guidance on QC and data        |                       |
|         |     analysis                       |                       |
+---------+------------------------------------+-----------------------+
| **P     |                                    |                       |
| lanning |                                    |                       |
| for     |                                    |                       |
| MAQC    |                                    |                       |
| Manusc  |                                    |                       |
| ripts** |                                    |                       |
| Chair:  |                                    |                       |
| Leming  |                                    |                       |
| Shi     |                                    |                       |
+---------+------------------------------------+-----------------------+
| 11:30   | 1.  Editorial                      | Janet Woodcock/Dan    |
| am      |                                    | Casciano              |
|         | 2.  FDA's VGDS and IPRG            |                       |
|         |                                    | Felix                 |
|         | 3.  MAQC main manuscript           | Fr                    |
|         |                                    | ueh/Federico/Sponsors |
|         | 4.  Reference RNA samples          |                       |
|         |                                    | Leming Shi (MAQC      |
|         | 5.  Sequence-based cross-platform  | Team)                 |
|         |     mapping                        |                       |
|         |                                    | James Fuscoe/Mike     |
|         | 6.  Normalization & gene selection | Wilson                |
|         |     methods                        |                       |
|         |                                    | Damir Herman/Roderick |
|         | 7.  Validation by alternative      | Jensen                |
|         |     technologies                   |                       |
|         |                                    | Leming Shi/Jim Chen   |
|         | 8.  Titration datasets             |                       |
|         |                                    | Federico Goodsaid     |
|         | 9.  Inter-laboratory variations    |                       |
|         |                                    | Richard Shippy        |
|         | 10. Cross-hybridization            |                       |
|         |                                    | Walter Liggett/Marc   |
|         | 11. One-color versus two-color     | Salit                 |
|         |     platforms                      |                       |
|         |                                    | Zoltan                |
|         | 12. Informatics tools for          | Szallasi/Roderick     |
|         |     regulatory review              | Jensen                |
|         |                                    |                       |
|         | 13. *Other topics to be suggested* | Tucker Patterson/Jim  |
|         |                                    | Collins               |
|         | Manuscript-drafting teams          |                       |
|         |                                    | Weida Tong            |
|         | Timeline                           |                       |
|         |                                    | *Participants*        |
|         | Journal                            |                       |
+---------+------------------------------------+-----------------------+
| 12:55   | Concluding remarks                 | Leming Shi            |
| pm      |                                    |                       |
+---------+------------------------------------+-----------------------+
| 1:00 pm | Adjourn                            |                       |
+---------+------------------------------------+-----------------------+
| *The    |                                    |                       |
| Cyprus  |                                    |                       |
| con     |                                    |                       |
| ference |                                    |                       |
| room    |                                    |                       |
| will be |                                    |                       |
| av      |                                    |                       |
| ailable |                                    |                       |
| until   |                                    |                       |
| 4:00 pm |                                    |                       |
| for     |                                    |                       |
| parti   |                                    |                       |
| cipants |                                    |                       |
| to      |                                    |                       |
| c       |                                    |                       |
| ontinue |                                    |                       |
| discu   |                                    |                       |
| ssion.* |                                    |                       |
+---------+------------------------------------+-----------------------+

**Location**:

The meeting will be held on December 1-2, 2005 at the **Cyprus Room**,
Crowne Plaza Cabana, 4290 El Camino Real, Palo Alto, CA 94306.
Telephone: 650-857-0787; FAX: 650-496-1939; Website:
<http://www.cppaloalto.crowneplaza.com/>. Please note the change of
meeting venue.

**Registration**:

Registration is free but required. Contact Leming Shi, National Center
for Toxicological Research, US FDA, 3900 NCTR Road, Jefferson, AR 72079.
Tel: 870-543-7387; <leming.shi@fda.hhs.gov>.

**Conference Call**:

A conference call has been set up to allow interested people to join the
meeting by telephone throughout the entire MAQC meeting. [**Dial-in
number: 888-566-5020** (international: +1-210-795-9594), **Passcode:
33297**]{.mark}. In fairness to the expected large audience in the Palo
Alto conference room, callers are asked to minimize the number and
length of their questions/comments because the audio quality may be less
than satisfactory. However, callers are encouraged to send their
questions/comments by e-mailing <weida.tong@fda.hhs.gov> and
<leming.shi@fda.hhs.gov>. We reserve the right to disconnect the
conference call if the audience in the Palo Alto conference room decides
that there is too much disruption by the calls. Thanks in advance for
your understanding.

**MAQC**:

<http://edkb.fda.gov/MAQC/> or

<http://www.fda.gov/nctr/science/centers/toxicoinformatics/maqc/>.

**ArrayTrack**:

<http://www.fda.gov/nctr/science/centers/toxicoinformatics/ArrayTrack/>

**Genomics \@FDA**:

<http://www.fda.gov/cder/genomics/>

**Stanford Genome Technology Center (SGTC)**:

<http://med.stanford.edu/sgtc/>

**ERRC (The External RNA Controls Consortium)**:

<http://www.cstl.nist.gov/biotech/ERCC/testplan.htm>

**NIST's Metrology for Gene Expression Program**:

<http://www.cstl.nist.gov/biotech/Cell&TissueMeasurements/GeneExpression.htm>

**Co-sponsors**: The MAQC (MicroArray Quality Control) project meeting
is co-sponsored by the US Food and Drug Administration and Stanford
Genome Technology Center of Stanford University.

![](media/image5.png)

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height="0.2569444444444444in"}

![](media/image4.png){width="2.9069444444444446in"
height="0.22777777777777777in"}

**The MAQC Project: Establishing Calibrated RNA Samples, Reference
Datasets, and QC Metrics/Thresholds for Microarray Quality Control**

FDA's Critical Path Initiative
(<http://www.fda.gov/oc/initiatives/criticalpath/>) identifies
pharmacogenomics as a key opportunity in advancing medical product
development and personalized medicine. FDA issued the "*Guidance for
Industry: Pharmacogenomic Data Submissions*"
(<http://www.fda.gov/cder/guidance/6400fnl.pdf>) to facilitate
scientific progress in the field of pharmacogenomics and to facilitate
the use of pharmacogenomic data in drug development and medical
diagnostics. Microarrays represent a core technology in
pharmacogenomics; however, before this technology can successfully and
reliably be applied in clinical practice and regulatory decision-making,
standards and quality measures need to be developed.

The MicroArray Quality Control (MAQC) project involves six FDA Centers,
major providers of microarray platforms and RNA samples, government
agencies, academic laboratories, and other stakeholders. The MAQC
project (Figure 1) aims to evaluate QC metrics and thresholds for
objectively assessing the performance achievable by various microarray
platforms and evaluating the advantages and disadvantages of various
data analysis methods. Two RNA samples will be selected for three
species (*i.e*., human, rat, and mouse), and differential gene
expression levels between the two samples will be calibrated with
microarrays and other technologies (*e.g*., QRT-PCR). The resulting
microarray datasets will be used for assessing the precision and
cross-platform/laboratory comparability of microarrays, and the QRT-PCR
datasets will enable evaluation of the nature and magnitude of any
systematic biases that may exist between microarrays and QRT-PCR. The
availability of the calibrated RNA samples and the resulting microarray
and QRT-PCR datasets, which will be made readily accessible to the
microarray community, will allow individual laboratories to more easily
identify and correct procedural failures. The implementation and
progress of the MAQC project is shown in Figure 2. The MAQC project will
help improve the microarray technology and foster its proper
applications in discovery, development and review of FDA regulated
products.

![](media/image2.wmf)

**Figure 1: An overview of the MAQC project.**

![](media/image2.wmf)

**Figure 2: The implementation and progress of the MAQC project.**

![](media/image2.wmf)

**Figure 3: Participants in the MAQC project.**

Table 1. An outline of manuscripts proposed as a special journal issue
on Microarray Quality Control ([draft; for discussion only]{.mark})

+---+------------+------------------------------------------+-----------+
| * | *          | **Contents**                             | **M       |
| * | *Tentative |                                          | anuscript |
| N | Title**    |                                          | Team**    |
| o |            |                                          |           |
| . |            |                                          |           |
| * |            |                                          |           |
| * |            |                                          |           |
+---+------------+------------------------------------------+-----------+
| 1 | Pharma     | -   Editorial to this Special Issue on   | **Janet   |
|   | cogenomics |     microarray quality control;          | W         |
|   | and the US |                                          | oodcock** |
|   | FDA's      | -   The importance of pharmacogenomics   | (Deputy   |
|   | Critical   |     in medical product development and   | Comm      |
|   | Path       |     personalized medicine (as stated in  | issioner, |
|   | Initiative |     the FDA's Critical Path Initiative); | FDA)      |
|   | to Medical |                                          |           |
|   | Product    | -   The reliability of technologies is   | Dan       |
|   | De         |     essential to realize the promises of | Casciano  |
|   | velopment: |     pharmacogenomics.                    | (         |
|   | Technol    |                                          | Director, |
|   | ogy-driven |                                          | FDA/NCTR) |
|   | I          |                                          |           |
|   | nnovations |                                          |           |
+---+------------+------------------------------------------+-----------+
| 2 | Impl       | -   Implementation of the VGDS mechanism | **Felix   |
|   | ementation |     at the FDA for sponsors to           | Frueh**   |
|   | of the     |     voluntarily submit genomic data      |           |
|   | FDA's      |     (including data management,          | Federico  |
|   | Voluntary  |     analysis, visualization, and         | Goodsaid  |
|   | Genomic    |     interpretation; training of FDA      |           |
|   | Data       |     reviewers; interactions between FDA  | Weida     |
|   | S          |     and sponsors);                       | Tong      |
|   | ubmissions |                                          |           |
|   | (VGDS)     | -   Lessens learned from several VGDS    | Sponsors  |
|   | Mechanism: |     case studies;                        |           |
|   | Guidelines |                                          |           |
|   | on         | -   Illustration of the challenges in    |           |
|   | microarray |     the regulatory review of             |           |
|   | quality    |     pharmacogenomic data: quality        |           |
|   | control    |     control of microarray experiments    |           |
|   | and data   |     and guidance on data analysis.       |           |
|   | analysis   |                                          |           |
|   | are        |                                          |           |
|   | essential  |                                          |           |
+---+------------+------------------------------------------+-----------+
| 3 | The MAQC   | -   Overview of the MAQC project:        | **Leming  |
|   | Project:   |     Pilot-I; Pilot-II; Main Study        | Shi**     |
|   | Es         |     (\~1000 arrays);                     |           |
|   | tablishing |                                          | Mike      |
|   | Calibrated | -   Uniqueness and deliverables of the   | Wilson    |
|   | RNA        |     MAQC project;                        |           |
|   | Samples,   |                                          | Uwe       |
|   | Reference  | -   Quality control metrics and          | Scherf    |
|   | Datasets,  |     thresholds for assessing the         |           |
|   | and QC     |     performance of each platform;        | Laura     |
|   | Metrics    |                                          | Reid      |
|   | /Threshold | -   Microarray cross-platform            |           |
|   | for        |     comparability;                       |           |
|   | MicroArray |                                          |           |
|   | Quality    | -   Concordance with alternative         |           |
|   | Control    |     technologies (TaqMan, QuantiGene,    |           |
|   |            |     and StaRT-PCR);                      |           |
|   | ("MAQC     |                                          |           |
|   | Main       | -   Correlation of step-by-step QC data  |           |
|   | Ma         |     with overall quality of microarray   |           |
|   | nuscript") |     data;                                |           |
|   |            |                                          |           |
|   |            | -   Relative accuracy based on titration |           |
|   |            |     datasets;                            |           |
|   |            |                                          |           |
|   |            | -   Next steps for the MAQC project:     |           |
|   |            |     mouse and rat; beyond total RNA.     |           |
+---+------------+------------------------------------------+-----------+
| 4 | Es         | -   MAQC Pilot-I: Selection of two RNA   | **Jim     |
|   | tablishing |     samples as the reference materials   | Fuscoe**  |
|   | Well-      |     using six objective criteria (based  |           |
|   | calibrated |     on data from 160 arrays on four      | Mike      |
|   | Reference  |     microarray platforms): (A)           | Wilson    |
|   | RNA        |     Stratagene Universal Human Reference |           |
|   | Samples as |     RNA and (B) Ambion Human Brain       | Gavin     |
|   | an         |     Reference RNA were selected;         | Fischer   |
|   | Efficient  |                                          |           |
|   | Quality    | -   Characteristics of the two RNAs:     |           |
|   | Control    |     quality, purity, stability,          |           |
|   | Tool for   |     availability, and reproducibility;   |           |
|   | Qu         |                                          |           |
|   | antitative | -   Characterization by microarray gene  |           |
|   | Gene       |     expression profiling;                |           |
|   | Expression |                                          |           |
|   | Profiling  | -   Protocols on the applications of the |           |
|   |            |     reference RNA samples.               |           |
+---+------------+------------------------------------------+-----------+
| 5 | Probe      | -   Mapping probe sequences of each      | **Damir   |
|   | Sequence   |     platform to the 9/26/2005 release of | Herman**  |
|   | Based      |     RefSeq database;                     |           |
|   | Mapping    |                                          | Rick      |
|   | across     | -   Statistics on the probe-target       | Jensen    |
|   | Microarray |     mapping;                             |           |
|   | Platforms: |                                          | Scott     |
|   | "Are they  | -   Handling different mapping           | Pine      |
|   | measuring  |     scenarios: (A) one probe -- one      |           |
|   | the same   |     target; (B) multiple probes -- one   | Zoltan    |
|   | things?"   |     target; (C) one probe -- multiple    | Szallasi  |
|   |            |     targets; and (D) multiple probes --  |           |
|   |            |     multiple targets;                    |           |
|   |            |                                          |           |
|   |            | -   Relationship between proximity of    |           |
|   |            |     probes from different platforms and  |           |
|   |            |     cross-platform consistency;          |           |
|   |            |                                          |           |
|   |            | -   Web access to probe sequences and    |           |
|   |            |     cross-platform mapping indices.      |           |
+---+------------+------------------------------------------+-----------+
| 6 | Impact of  | -   Normalization methods: raw; total    | **Leming  |
|   | Nor        |     (mean) intensity; median intensity;  | Shi**     |
|   | malization |     quantile; Affymetrix specific --     |           |
|   | and Gene   |     MAS5, dCHIP, RMA, PLIER, and their   | Xu Guo    |
|   | Selection  |     variants;                            |           |
|   | Methods on |                                          | Wenjun    |
|   | Microarray | -   Gene selection methods: fold change, | Bao       |
|   | Studies    |     *p*-value, fold change + *p*-value,  |           |
|   |            |     SAM, FDR, Others;                    | Rick      |
|   |            |                                          | Jensen    |
|   |            | -   Impact of the different combinations |           |
|   |            |     of normalization and gene selection  | *Lisa     |
|   |            |     methods on the stability of the      | Croner*   |
|   |            |     "significant gene list" from the     |           |
|   |            |     same platform;                       | *Rafael   |
|   |            |                                          | Irizarry* |
|   |            | -   Impact on microarray cross-platform  |           |
|   |            |     comparability;                       | Jim Chen  |
|   |            |                                          |           |
|   |            | -   Identification of a reliable/stable  |           |
|   |            |     "significant gene list";             |           |
|   |            |                                          |           |
|   |            | -   Impact of different ways of handling |           |
|   |            |     background and offset values.        |           |
+---+------------+------------------------------------------+-----------+
| 7 | Validation | -   Unbiased selection of 1000 genes for | *         |
|   | of         |     TaqMan validation;                   | *Federico |
|   | Microarray |                                          | G         |
|   | Results    | -   Unbiased selection of 200 genes for  | oodsaid** |
|   | with       |     QuantiGene and StaRT-PCR validation; |           |
|   | A          |                                          | Kathy Lee |
|   | lternative | -   Consistency across technology        |           |
|   | Te         |     platforms;                           | Yuling    |
|   | chnologies |                                          | Luo       |
|   |            | -   Identification of the most           |           |
|   |            |     discordant genes across platforms;   | Jim       |
|   |            |                                          | Willey    |
|   |            | -   Design of new assays for explaining  |           |
|   |            |     the discrepancies.                   |           |
+---+------------+------------------------------------------+-----------+
| 8 | The Use of | -   MAQC Pilot-II: Selecting two of the  | **Rich    |
|   | Titration  |     13 titration points for the main     | Shippy**  |
|   | Datasets   |     study (200 arrays plus TaqMan and    |           |
|   | to Assess  |     QuantiGene assays for 10 genes);     | Shawn     |
|   | the        |                                          | Baker     |
|   | Accuracy   | -   MAQC Main Study: Two titration       |           |
|   | of         |     points (75:25 and 25:75,             | Paul      |
|   | Microarray |     SUHRR:ABHRR);                        | Wolber    |
|   | Platforms  |                                          |           |
|   |            | -   Expected versus observed fold        | Yuling    |
|   |            |     changes (including mathematical      | Luo       |
|   |            |     formulas);                           |           |
|   |            |                                          | Rick      |
|   |            | -   The use of titration data to         | Jensen    |
|   |            |     evaluate normalization methods.      |           |
+---+------------+------------------------------------------+-----------+
| 9 | Charac     | -   Sources of technical variation that  | **Walter  |
|   | terization |     affect many genes;                   | Liggett** |
|   | of         |                                          |           |
|   | Intra      | -   Inter-laboratory comparison          | David     |
|   | -platform, |     approaches that encompass many       | Duewer    |
|   | Inter-     |     genes;                               |           |
|   | laboratory |                                          | Marc      |
|   | V          | -   Surprising aspects of                | Salit     |
|   | ariability |     inter-laboratory differences;        |           |
|   |            |                                          |           |
|   |            | -   Confirmation by manufacturer         |           |
|   |            |     spike-ins (if this contributes to    |           |
|   |            |     the characterization).               |           |
+---+------------+------------------------------------------+-----------+
| 1 | Modeling   | -   Probe sequence based models to       | **Zoltan  |
| 0 | Cross-hyb  |     estimate the affinity between probe  | S         |
|   | ridization |     and target;                          | zallasi** |
|   | of         |                                          |           |
|   | Microarray | -   Probe sequence based models to       | Rick      |
|   | E          |     estimate the level of tendency of    | Jensen    |
|   | xperiments |     cross hybridization;                 |           |
|   |            |                                          |           |
|   |            | -   Target sequence based methods to     |           |
|   |            |     estimate the effect of secondary     |           |
|   |            |     structure of microarray              |           |
|   |            |     hybridization.                       |           |
+---+------------+------------------------------------------+-----------+
| 1 | One-color  | -   Philosophical considerations on      | **Tucker  |
| 1 | versus     |     microarray experimental designs:     | Pa        |
|   | Two-color  |     two-color vs one-color;              | tterson** |
|   | Designs in |                                          |           |
|   | Microarray | -   Common reference design vs           | Jim       |
|   | E          |     sample-pairing design;               | Collins   |
|   | xperiments |                                          |           |
|   |            | -   Dye biases and dye-swaps;            | Francoise |
|   |            |                                          | de        |
|   |            | -   One-color hybridizations run on a    | Lo        |
|   |            |     two-color platform;                  | ngueville |
|   |            |                                          |           |
|   |            | -   Ratio- and intensity-based data      | Hong Fang |
|   |            |     analysis for two-color design.       |           |
|   |            |                                          | Tao Han   |
|   |            |                                          |           |
|   |            |                                          | Jing Han  |
|   |            |                                          |           |
|   |            |                                          | Ernie     |
|   |            |                                          | Kawasaki  |
+---+------------+------------------------------------------+-----------+
| 1 | I          | -   ArrayTrack as a tool for regulatory  | **Weida   |
| 2 | nformatics |     review of pharmacogenomic data       | Tong**    |
|   | Tools for  |     submissions;                         |           |
|   | Utilizing  |                                          | Hong Fang |
|   | the MAQC   | -   Assessing laboratory proficiency by  |           |
|   | Datasets   |     comparing its data against the MAQC  | Federico  |
|   | for        |     benchmark datasets;                  | Goodsaid  |
|   | Microarray |                                          |           |
|   | Quality    | -   Assessing the quality of individual  |           |
|   | Control    |     arrays by examining the performance  |           |
|   |            |     of spike-in controls.                |           |
+---+------------+------------------------------------------+-----------+

**Timeline:**

1.  **May 31, 2006**: Submission of MAQC manuscripts; Public release of
    MAQC datasets.

2.  **July-September 2006**: Publication of MAQC manuscripts.

**MAQC Timeline**

3.  **April 28, 2004**: Leming Shi submitted a Concept Paper (brief
    proposal) to FDA/NCTR director on "*Establishing Quality Assurance
    and Quality Control (QA/QC) Criteria for DNA Microarray
    Measurements*". Multiple FDA Centers were invited to participate.

4.  **June 10, 2004**: The Microarray QC concept paper was approved
    (project#: E0720701).

5.  **September 24, 2004**: Felix Frueh and Federico Goodsaid (FDA/CDER)
    were invited to visit FDA/NCTR. A wide range of issues and
    challenges regarding the use of genomic data in regulatory review
    were extensively discussed.

6.  **October 2004**: Major microarray platform providers and RNA
    companies were invited.

7.  **October 22, 2004**: *Science* published "Getting the noise out of
    gene arrays", raising concerns about the reliability of microarray
    data.

8.  **February 11, 2005**: The first face-to-face meeting was held at
    FDA/NCTR, Jefferson, Arkansas. In the meeting summary (dated
    February 16, 2005), Leming Shi named the project as "MAQC"
    ([M]{.underline}icro[A]{.underline}rray [Q]{.underline}uality
    [C]{.underline}ontrol). Regular biweekly teleconferences have been
    set up to keep track of the MAQC project.

9.  **March 22, 2005**: FDA released the final version the "*Guidance
    for Industry: Pharmacogenomic Data Submissions*"
    (<http://www.fda.gov/cder/guidance/6400fnl.pdf>) to facilitate
    scientific progress in the field of pharmacogenomics and to
    facilitate the use of pharmacogenomic data in drug development and
    medical diagnostics.

10. **March 27, 2005**: Full proposal under the title "The MAQC
    (Microarray Quality Control) Project" was submitted to FDA/NCTR
    director.

11. **April 2005**: Pilot-I (RNA Sample Selection) data generation was
    completed.

12. **May 2-3, 2005**: The second face-to-face meeting was held at
    FDA/CDER, Rockville, MD. Decisions were made on RNA sample selection
    and the design of the main study.

13. **May 3, 2005**: The full MAQC protocol was approved by FDA/NCTR
    director.

14. **June 2005**: The MAQC website was set up:
    <http://edkb.fda.gov/MAQC/>.

15. **July 2005**: Pilot-II (Tissue Titration) data generation was
    completed.

16. **July 15, 2005**: "Cross-platform comparability of microarray
    technology: intra-platform consistency and appropriate data analysis
    procedures are essential" (Shi L. *et al*.) was published in *BMC
    Bioinformatics*, illustrating the importance of the MAQC project on
    quality control and data analysis.

17. **August 22, 2005**: Main study RNA samples were shipped to test
    sites.

18. **October 21, 2005**: Main study data were generated and submitted
    to FDA/NCTR.

19. **October 25, 2005**: Data from AFX, AGL, ABI, GEH, and ILM were
    distributed to 27 test sites and 10 data analysis sites.

20. **November 4, 2005**: Data from EPP, NCI, TAQ, QGN, and GEX were
    distributed.

21. **November 28, 2005**: Agilent one-color data (AG1) were
    distributed.

22. **December 1-2, 2005**: The third face-to-face meeting will be held
    in Palo Alto, CA to discuss results on the analysis of the MAQC
    datasets and plans for publications.

23. **May 31, 2006**: Submission of MAQC manuscripts; Public release of
    the datasets.

24. **July-September 2006**: Publication of MAQC manuscripts.

25. **December 2006**: Public meeting on microarray quality control and
    data analysis.

26. **December 2007**: Guidance on microarray quality control and data
    analysis.

**Table 2. List of Registered MAQC Meeting Participants**

As of 7:00 AM PST, November-29-2005, 100 people have registered to
attend the MAQC project meeting in Palo Alto, CA. For those who plan to
attend the meeting via conference call, please contact
<Leming.Shi@fda.hhs.gov> so that your name will be added to the list of
participants in the meeting summary.

  --------- ------------------ ------------------- --------------------------------------
  **No.**   **Name**           **Organization**    **E-mail**

  1         Aschheim, Kathy    Nature              k.aschheim@natureny.com
                               Biotechnology       

  2         Austermiller,      Ohio Medical        
            Bradley            University          

  3         Baker, Shawn C.    Illumina            scbaker@illumina.com

  4         Bao, Wenjun        SAS                 wenjun.bao@sas.com

  5         Beneke, Ralph      Tecan               ralph.beneke@tecan.com

  6         Bertholet, Vincent Eppendorf           bertholet.v@eppendorf.be

  7         Bjeldanes, Erik    Agilent             erik_bjeldanes@agilent.com

  8         Boysen, Cecilie    ViaLogy             cecilie.boysen@vialogy.com

  9         Bremer, Eric       Northwestern        egbremer@northwestern.edu
                               University          

  10        Bromley, Bud       ViaLogy             bud.bromley@vialogy.com

  11        Broudy, Thomas     Affymetrix          thomas_broudy@affymetrix.com

  12        Chen, Luke         PhalanxBio          

  13        Chen, Michelle     Agilent             

  14        Chen, Rong         Stanford University rchen1@stanford.edu

  15        Chu, Tzu-Ming      SAS                 tzu-ming.chu@sas.com

  16        Chudin, Eugene     Illumina            echudin@illumina.com

  17        Coleman, Jeannette FDA/NCTR            jcoleman@nctr.fda.gov
            F.                                     

  18        Collins, Jim       Agilent             jim_collins@agilent.com

  19        Conard, Wes        Affymetrix          wes_conard@affymetrix.com

  20        Croner, Lisa J.    Biogen Idec         lisa.croner@biogenidec.com

  21        Davies,            Affymetrix          christopher_davies@affymetrix.com
            Christopher                            

  22        Davis, Ronald W.   Stanford University dbowe@stanford.edu

  23        de Longueville,    Eppendorf           delongueville.f@eppendorf.be
            Francoise                              

  24        DeSesa, Catherine  Northwestern        cdesesa@luc.edu
                               University          

  25        Dick, Daren        TeleChem ArrayIt    daren@biosearchtech.com

  26        Dragan, Yvonne P.  FDA/NCTR            yvonne.dragan@fda.hhs.gov

  27        Falduto, Mike      GenUs BioSystems    mfalduto@genusbiosystems.com

  28        Fischer, Gavin M.  Stratagene          gavin.fischer@stratagene.com

  29        Friedman, Milt     TeleChem ArrayIt    miltfriedman@earthlink.net

  30        Fulmer-Smentek,    Agilent             
            Stephanie                              

  31        Fuscoe, James C.   FDA/NCTR            james.fuscoe@fda.hhs.gov

  32        Goodsaid, Federico FDA/CDER            federico.goodsaid@fda.hhs.gov
            M.                                     

  33        Guo, Xu            Affymetrix          xu_guo@affymetrix.com

  34        Hager, Janet       Yale University     janet.hager@yale.edu

  35        Haje, Paul K.      TeleChem ArrayIt    paul@arrayit.com

  36        Herman, Damir      NIH/NCBI            herman@ncbi.nlm.nih.gov

  37        Jacobson, James W. Luminex             daves@luminexcorp.com

  38        Jensen, Roderick   UMass Boston        roderick.jensen@umb.edu
            V.                                     

  39        Ji, Hanlee         Stanford University hanleeji@stanford.edu

  40        Jokhadze, George   PhalanxBio          

  41        Jones, Wendell     Expression Analysis wjones@expressionanalysis.com

  42        Kalush, Francis    FDA/CDRH            fxk@cdrh.fda.gov

  43        Kao, Pail          PhalanxBio          

  44        Kawasaki, Ernest   NIH/NCI             kawasake@mail.nih.gov
            S.                                     

  45        Knight, Charles    Ohio Medical        
                               University          

  46        Kohne, Connie      Jaden BioScience    ckohne@san.rr.com

  47        Kohne, David       Jaden BioScience    drkohne@gmail.com

  48        Kumm, Jochen       Stanford University Jochen.kumm@stanford.edu

  49        Kuo, Winston       Harvard University  wkuo@genetics.med.harvard.edu

  50        Lee, Kathy Y.      Applied Biosystems  kathy.y.lee@appliedbiosystems.com

  51        Li, Li             Stanford University l3li@stanford.edu

  52        Li, Quan           UT Southwestern     quan.li@utsouthwestern.edu

  53        Liggett, Walter    NIST                walter.liggett@nist.gov

  54        Liu, Chunmei       Affymetrix          chunmei_liu@affymetrix.com

  55        Liu, Wei-min       Roche               wei-min.liu@roche.com

  56        Lobenhofer, Edward Icoria              elobenhofer@icoria.com
            K.                                     

  57        Lucas, Anne        Agilent             

  58        Luo, Yuling        Genospectra         yluo@genospectra.com

  59        Ma, Charles        PhalanxBio          charlesma@phalanxbiotech.com

  60        Ma, Yunqing        Genospectra         yma@genospectra.com

  61        Magnuson, Scott R. GenUs BioSystems    smagnuson@genusbiosystems.com

  62        Mansfield, Elaine  Stanford University elainems@stanford.edu

  63        Martinsky, Todd J. TeleChem ArrayIt    todd@arrayit.com

  64        Mehta, Kshama      Agilent             

  65        O\'Leary, Dan      Nichols Institute   olearyd@nicholsdiag.com
                               Diagnostics         

  66        Peters, Elizabeth  Gene Express        ehpeters@gmail.com
            H.                                     

  67        Peterson, Ron      Novartis            ron.peterson@novartis.com

  68        Pine, Scott        FDA/CDER            patrick.pine@fda.hhs.gov

  69        Reid, Laura        Expression Analysis lreid@expressionanalysis.com

  70        Ren, Hongzu        EPA                 ren.hongzu@epamail.epa.gov

  71        Salit, Marc        NIST                salit@nist.gov

  72        Samaha, Ray R.     Applied Biosystems  raymond.samaha@appliedbiosystems.com

  73        Schena, Mark       TeleChem ArrayIt    mark@arrayit.com

  74        Schroth, Gary P    Solexa              gschroth@solexa.com

  75        Setterquist,       Ambion              bsetterquist@ambion.com
            Robert A.                              

  76        Shchegrova,        Agilent             svetlana_shchegrova@agilent.com
            Svetlana                               

  77        Shi, Leming        FDA/NCTR            leming.shi@fda.hhs.gov

  78        Shippy, Richard    GE Healthcare       richard.shippy@ge.com

  79        Slikker, Jr.,      FDA/NCTR            william.slikker@fda.hhs.gov
            William                                

  80        Smith, Dave D.     Luminex             daves@luminexcorp.com

  81        Sun, Yongming      Applied Biosystems  sunya@appliedbiosystems.com

  82        Suzuki, Greg       TeleChem ArrayIt    greg@arrayit.com

  83        Thierry-Mieg,      NIH/NCBI            dthierre@ncbi.nlm.nih.gov
            Danielle                               

  84        Thierry-Mieg, Jean NIH/NCBI            mieg@ncbi.nlm.nih.gov

  85        Thompson, Karol L. FDA/CDER            karol.thompson@fda.hhs.gov

  86        Tong, Weida        FDA/NCTR            weida.tong@fda.hhs.gov

  87        Turpaz, Yaron      Affymetrix          yaron_turpaz@affymetrix.com

  88        Walker, Stephen J. Wake Forest         swalker@wfubmc.edu
                               University          

  89        Wang, Charles      UCLA/Cedars-Sinai   charles.wang@cshs.org

  90        Warrington, Janet  Affymetrix          janet_warrington@affymetrix.com
            A.                                     

  91        Wicki, Roland      Applied Biosystems  roland.wicki@appliedbiosystems.com

  92        Willey, James C.   Gene Express (Ohio  jwilley@meduohio.edu
                               Medical Univ.)      

  93        Williams, Alan     Affymetrix          alan_williams@affymetrix.com

  94        Wilson, Mike       Ambion              mwilson@ambion.com

  95        Wolber, Paul K.    Agilent             paul_wolber@agilent.com

  96        Xiao, Chunlin      Applied Biosystems  chunlin.xiao@celera.com

  97        Yang, Jingping     SuperArray          jpyang@superarray.net

  98        Zhai, Jack         Applied Biosystems  jack.y.zhai@appliedbiosystems.com

  99        Zhang, Lu          Solexa              lzhang@solexa.com

  100       Zong, Sheng        UIUC                szhong@uiuc.edu

  101                                              

  102                                              

  103                                              

  104                                              

  105                                              
  --------- ------------------ ------------------- --------------------------------------