Minimum information about a microarray experiment MIAME November 2000

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Minimum information about a microarray experiment - MIAME

Endorsed by MGED steering committee meeting
November 17, 2000
For archive purposes

The goal of the MIAME is to specify the minimum information that must be reported about a microarray (or any DNA array) based gene expression monitoring experiment in order to ensure the interpretability, as well as potential verification of the results by third parties. The background aim is to facilitate the establishment of public repositories and data exchange format for microarray based gene expression data. The MGED group will be encouraging the scientific journals and funding agencies to adopt policies requiring data submissions to repositories, once MIAME compliant repositories are established.

Introduction:

The definition of the minimum information is aimed at co-operative data providers, and not for closing possible loopholes in not providing the information.

Among the concepts in the definition is a list of 'qualifier, value, source' triplets, where 'source' is either user defined, or a reference to an externally defined ontology or controlled vocabulary, such as the species taxonomy database at NCBI. Where necessary, the authors are encouraged to define their own qualifiers and provide the appropriate values so that the list as a whole gives sufficient information to interpret that particular part of the experiment. The judgement regarding the necessary level of detail is left to the data providers. In the future these 'voluntary' qualifier lists may be gradually substituted by required fields, as the respective ontologies are developed.

Parts of the MIAME can be provided as a reference or link to an externally existing description. For instance, for commercial or other standard arrays all the required information should be normally provided only once by the array provider and referenced by the users. Standard protocols should also normally be provided only once. It is necessary, that either a valid reference or the information itself be provided for every experiment set.

Definition:

The minimum information about a published microarray based gene expression experiment should include the description of

1.Experimental design: the set of the hybridisation experiments as a whole

2.Array design: each array used and each element (spot) on the array

3.Samples: samples used, the extract preparation and labeling

4.Hybridisations: procedures and parameters

5.Measurements: images, quantitation, specifications

6.Controls: types, values, specifications

The following details should be provided for each array, each sample, hybridisation and measurement in the experiment set:

1. Experimental design: the set of the hybridisation experiments as a whole

a)author (submitter), laboratory, contact information, links (URL)

b)type of the experiment - maximum one line for instance:

normal vs. diseased comparison

treated vs. untreated comparison

time course

dose response

effect of gene knock-out

effect of gene knock-in (transgenics)

shock

(multiple types possible)

c)experimental factors (e.g., time, dose, genetic variation)

d)the list of platforms used

e)single or multiple hybridisations

For multiple hybridisations:

ordered/unordered
serial (yes/no)

type (e.g., time course, dose response)

grouping (yes/no)

type (e.g., normal vs. diseased, multiple tissue comparison)

list of the samples and arrays used in the experiment and description of the relationship between them: each sample and each array should be assigned a unique id in the experiment set and all the relationships should be listed with appropriate comments
which hybridisations are replicates

f)quality related indicators

does a related peer-reviewed publication exist
number of replicate hybridisations
any other quality control steps taken (polyA, non-specific binding etc.)

g)optional user defined "qualifier, value, source" list (see Introduction)

h)a free text description of the experiment set or a link to a publication

2. Array design: each array used and each element (spot) on the array.

a)array

array design name (e.g., "Stanford Human 10K set")

platform type: in situ synthesized or spotted

provider (source)

surface type: adsorptive/ non-adsorptive

surface type name

array dimensions (long, short)

number of elements on the array

a reference system allowing each element (spot) to be located on the array (in the simplest case the number of columns and rows is sufficient)

unique ID from the provider

production protocol (obligatory if applicable)

optional "qualifier, value, source" list (see Introduction)

b)element (spot) on the array - elements may be simple, i.e., containing only identical molecules, or composite, i.e., containing different oligonucleotides obtained from the same reference molecule; for each element the following must be given:

position on the array allowing the spot to be identified in the image (see 5. a) below)

element type: synthesized oligonucleotides, PCR products, plasmids, colonies, other

clone information, obligatory for elements obtained from clones:

clone ID, clone provider, date, availability

sequence information, obligatory for simple synthetic elements:

sequence accession number in DDBJ/EMBL/GenBank if known
sequence itself (if databases do not contain it)

for composite oligonucleotide elements:

oligonucleotide sequences, if given
number of oligonucleotides and the reference sequence (or accession number), otherwise

approximate lengths if exact sequence not known

single or double stranded

element (spot) dimensions (approximate diameter)

element generation protocol that includes sufficient information to reproduce the element

attachment (covalent/ionic/other)

gene name and links to appropriate databases (e.g., SWISS-PROT, or organism specific databases), if applicable

3. Samples: samples used, extract preparation and labeling

a)sample source and treatment:

organism (NCBI taxonomy)

additional "qualifier, value, source" list; each qualifier in the list is obligatory if applicable; the list includes:

cell source and type (if derived from primary sources (s))
sex
age
development stage
organism part (tissue)
animal/plant strain or line
genetic variation (e.g., gene knockout, transgenic variation)
individual
individual genetic characteristics (e.g., disease alleles, polymorphisms)
disease state or normal
target cell type
cell line and source (if applicable)
in vivo treatments (organism or individual treatments)
in vitro treatments (cell culture conditions)
treatment type (e.g., small molecule, heat shock, cold shock, food deprivation)
compound
separation technique (e.g., none, trimming, microdissection, FACS)

laboratory protocol for sample treatment

b)hybridisation extract preparation

laboratory protocol for extract preparation, including:

extraction method
whether total RNA, mRNA, or genomic DNA is extracted
amplification (RNA polymerases, PCR)

optional "qualifier, value, source" list (see Introduction)

c)labeling

laboratory protocol for labelling, including:

amount of nucleic acids labeled
exogenous sequences (spikes) added
label used (e.g., Cy3, Cy5, 33P)

optional "qualifier, value, source" list (see Introduction)

4. Hybridisations: procedures and parameters

laboratory protocol for hybridisation, including:

the solution (e.g., concentration of solutes)
blocking agent
wash procedure
quantity of labelled target used
time, concentration, volume, temperature
description of the hybridisation instruments

optional "qualifier, value, source" list (see Introduction)

5. Measurements: images, quantitation, specifications:

a)hybridisation scan raw data:

a1)the scanner image file (e.g., TIFF) from the hybridised microarray scanning

a2)scanning information:

parsed header of the TIFF file, including laser power, spatial resolution, pixel space, PMT voltage;
laboratory protocol for scanning, including:
scanning hardware
scanning software

b)image analysis and quantitation

b1)the complete image analysis output (of the particular image analysis software) for each element (or composite element - see 2.b), for each channel

b2)image analysis information:

image analysis software specification and version, availability, and the description of the algorithm
all parameters

c)summarized information from possible replicates

c1)derived measurement value summarizing related elements as used by the author (this may constitute replicates of the element on the same or different arrays or hybridisations, as well as different elements related to the same entity e.g., gene)

c2)reliability indicator for the value of c1) as used by the author (e.g., standard deviation); may be "unknown"

c3)specification how c1 and c2 are calculated; the specification should be bases on b1

6. Normalisation controls, values, specifications for hybridisations

a)Normalization strategy

spiking

"housekeeping gene"

total array

optional used defined "quality, value, source" list

b)Normalisation algorithm

linear regression

log-linear regression

ratio statistics

log(ratio) mean/median centering

nonlinear regression

optional used defined "quality, value, source" list

c)Control array elements

array and position (the abstract coordinate on the array)

control type (spiking, normalization, negative, positive)

control qualifier (endogenous, exogenous)

optional used defined "quality, value, source" list

d)Hybridisation extract preparation

spike type

spike qualifier

target element

optional used defined "quality, value, source" list

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