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pmid:21092329

Validation and characterization of DNA microarray gene expression data distribution and associated moments.

Reuben Thomas · Luis de la Torre · Xiaoqing Chang · Sanjay Mehrotra

BMC bioinformatics · 2010 doi:10.1186/1471-2105-11-576

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title
Validation and characterization of DNA microarray gene expression data distribution and associated moments.
doi
10.1186/1471-2105-11-576
pmid
21092329
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[0]
Reuben Thomas
[1]
Luis de la Torre
[2]
Xiaoqing Chang
[3]
Sanjay Mehrotra
journal
BMC bioinformatics
year
2010
abstract
BACKGROUND: The data from DNA microarrays are increasingly being used in order to understand effects of different conditions, exposures or diseases on the modulation of the expression of various genes in a biological system. This knowledge is then further used in order to generate molecular mechanistic hypotheses for an organism when it is exposed to different conditions. Several different methods have been proposed to analyze these data under different distributional assumptions on gene expression. However, the empirical validation of these assumptions is lacking. RESULTS: Best fit hypotheses tests, moment-ratio diagrams and relationships between the different moments of the distribution of the gene expression was used to characterize the observed distributions. The data are obtained from the publicly available gene expression database, Gene Expression Omnibus (GEO) to characterize the empirical distributions of gene expressions obtained under varying experimental situations each of which providing relatively large number of samples for hypothesis testing. All data were obtained from either of two microarray platforms--the commercial Affymetrix mouse 430.2 platform and a non-commercial Rosetta/Merck one. The data from each platform were preprocessed in the same manner. CONCLUSIONS: The null hypotheses for goodness of fit for all considered univariate theoretical probability distributions (including the Normal distribution) are rejected for more than 50% of probe sets on the Affymetrix microarray platform at a 95% confidence level, suggesting that under the tested conditions a priori assumption of any of these distributions across all probe sets is not valid. The pattern of null hypotheses rejection was different for the data from Rosetta/Merck platform with only around 20% of the probe sets failing the logistic distribution goodness-of-fit test. We find that there are statistically significant (at 95% confidence level based on the F-test for the fitted linear model) relationships between the mean and the logarithm of the coefficient of variation of the distributions of the logarithm of gene expressions. An additional novel statistically significant quadratic relationship between the skewness and kurtosis is identified. Data from both microarray platforms fail to identify with any one of the chosen theoretical probability distributions from an analysis of the l-moment ratio diagram.
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In this manuscript the results for the AD are provided while those for the KS tests are provided in the Additional material.
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The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30].
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sections[3] "Data sets used in the analysis" paragraph 2
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The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30].
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[30]
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[92]
GSM207890
sample_count
93
group_sizes
null
group_sizes_basis
null
platform
1261
taxon
Mus musculus
title
Effect of Synthetic Dietary Triglycerides: a Novel Research Paradigm for Nutrigenomics
resolution_checked_at
2026-11-01T15:30:21Z
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[4] object · 15 fields
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The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30].
structure object · 15 fields
repository
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access_route
GEO accession URL
access_statement_verbatim
The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30].
access_statement_kind
repository_route_statement
sample_accessions array · 131 items
[0]
GSM239832
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[25]
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[26]
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[27]
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[28]
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[29]
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[30]
GSM239862
[31]
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[32]
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[34]
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[42]
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[67]
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[68]
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[70]
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[74]
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[75]
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[76]
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[77]
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[78]
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[88]
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[89]
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[94]
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[95]
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[97]
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[98]
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[99]
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[100]
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[102]
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[104]
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[105]
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[107]
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[108]
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[109]
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[110]
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[111]
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[112]
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[115]
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[118]
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[119]
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[120]
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[121]
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[122]
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[123]
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[124]
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[125]
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[126]
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[127]
GSM239959
[128]
GSM239960
[129]
GSM239961
[130]
GSM239962
sample_count
131
group_sizes
null
group_sizes_basis
null
platform
1261
taxon
Mus musculus
title
Sleep deprivation and the brain
resolution_checked_at
2026-11-01T15:30:21Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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[5] object · 16 fields
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asset:table:pmid:21092329:1
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jats-table
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Description of the data sets used.
structure object · 5 fields
pmcid
PMC3002903
section_index
3
section_title
Data sets used in the analysis
row_count
12
column_count
6
table object · 8 fields
label
Table 1
caption
Description of the data sets used.
rows array · 12 items
[0] array · 6 items
[0]
Data set
[1]
GEO accession
[2]
Technology
[3]
No. of Samples
[4]
Tissue
[5]
Data
[1] array · 6 items
[0]
Craniofacial
[1]
GSE7759
[2]
in situ oligonucleotide
[3]
105
[4]
craniofacial
[5]
Logarithm of transcript measure
[2] array · 1 item
[0]
[3] array · 6 items
[0]
Liver
[1]
GSE8396
[2]
in situ oligonucleotide
[3]
93
[4]
liver
[5]
Logarithm of transcript measure
[4] array · 1 item
[0]
[5] array · 6 items
[0]
Brain
[1]
GSE9444
[2]
in situ oligonucleotide
[3]
69
[4]
brain
[5]
Logarithm of transcript measure
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[0]
[7] array · 6 items
[0]
Housekeeping
[1]
Additional file 4, Table S2
[2]
in situ oligonucleotide
[3]
6219
[4]
mixed
[5]
Logarithm of transcript measure
[8] array · 1 item
[0]
[9] array · 6 items
[0]
Male
[1]
GSE2814
[2]
spotted oligonucleotide
[3]
155
[4]
liver
[5]
Logarithm of transcript measure relative to common pool
[10] array · 1 item
[0]
[11] array · 6 items
[0]
Female
[1]
GSE2814
[2]
spotted oligonucleotide
[3]
156
[4]
liver
[5]
Logarithm of transcript measure relative to common pool
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Fraction of null hypotheses rejected by the Anderson-Darling tests for best fit to 7 distribution functions.
structure object · 5 fields
pmcid
PMC3002903
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8
section_title
Results
row_count
12
column_count
9
table object · 8 fields
label
Table 2
caption
Fraction of null hypotheses rejected by the Anderson-Darling tests for best fit to 7 distribution functions.
rows array · 12 items
[0] array · 9 items
[0]
Dataset
[1]
Probe set no.
[2]
Normal
[3]
Weibull
[4]
Extreme Value
[5]
Logistic
[6]
Lognormal
[7]
Log-logistic
[8]
At least one of the distributions not rejected
[1] array · 9 items
[0]
Craniofacial
[1]
6215
[2]
0.72
[3]
0.79
[4]
0.82
[5]
0.69
[6]
0.75
[7]
0.71
[8]
0.46
[2] array · 1 item
[0]
[3] array · 9 items
[0]
Liver
[1]
6228
[2]
0.82
[3]
0.93
[4]
0.95
[5]
0.79
[6]
0.83
[7]
0.8
[8]
0.25
[4] array · 1 item
[0]
[5] array · 9 items
[0]
Brain
[1]
25146
[2]
0.77
[3]
0.92
[4]
0.93
[5]
0.69
[6]
0.77
[7]
0.68
[8]
0.35
[6] array · 1 item
[0]
[7] array · 9 items
[0]
Housekeeping
[1]
23
[2]
0.7
[3]
1
[4]
1
[5]
1
[6]
0.48
[7]
1
[8]
0.52
[8] array · 1 item
[0]
[9] array · 9 items
[0]
Male
[1]
19532
[2]
0.46
[3]
NA
[4]
0.96
[5]
0.24
[6]
NA
[7]
NA
[8]
0.82
[10] array · 1 item
[0]
[11] array · 9 items
[0]
Female
[1]
18915
[2]
0.43
[3]
NA
[4]
0.96
[5]
0.21
[6]
NA
[7]
NA
[8]
0.85
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section[8]/table-wrap[1]#T2
[7] object · 16 fields
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asset:table:pmid:21092329:3
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jats-table
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Coefficients of the linear trends between the logarithm of the coefficient of variation (CV) and the mean of the distribution of the logarithm of gene expression for each of the three data sets.
structure object · 5 fields
pmcid
PMC3002903
section_index
8
section_title
Results
row_count
10
column_count
5
table object · 8 fields
label
Table 3
caption
Coefficients of the linear trends between the logarithm of the coefficient of variation (CV) and the mean of the distribution of the logarithm of gene expression for each of the three data sets.
rows array · 10 items
[0] array · 5 items
[0]
Data set
[1]
Intercept
[2]
Slope
[3]
R2
[4]
p-value
[1] array · 5 items
[0]
Craniofacial
[1]
-1.38 ± 0.06
[2]
-0.20 ± 0.01
[3]
0.6
[4]
0
[2] array · 1 item
[0]
[3] array · 5 items
[0]
Liver
[1]
-1.99 ± 0.11
[2]
-0.19 ± 0.02
[3]
0.44
[4]
0
[4] array · 1 item
[0]
[5] array · 5 items
[0]
Brain
[1]
-2.10 ± 0.04
[2]
-0.22 ± 0.01
[3]
0.62
[4]
0
[6] array · 1 item
[0]
[7] array · 5 items
[0]
Male
[1]
0.57 ± 0.02
[2]
-1.67 ± 0.12
[3]
0.29
[4]
0
[8] array · 1 item
[0]
[9] array · 5 items
[0]
Female
[1]
0.56 ± 0.02
[2]
-1.74 ± 0.13
[3]
0.3
[4]
0
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section[8]/table-wrap[2]#T3
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Means of skewness and kurtosis of distribution of log of gene expression.
structure object · 5 fields
pmcid
PMC3002903
section_index
8
section_title
Results
row_count
10
column_count
3
table object · 8 fields
label
Table 4
caption
Means of skewness and kurtosis of distribution of log of gene expression.
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[0] array · 3 items
[0]
Data set
[1]
Mean skewness
[2]
Mean kurtosis
[1] array · 3 items
[0]
Craniofacial
[1]
-0.39 ± 0.03
[2]
4.02 ± 0.12
[2] array · 1 item
[0]
[3] array · 3 items
[0]
Liver
[1]
-0.16 ± 0.03
[2]
3.82 ± 0.08
[4] array · 1 item
[0]
[5] array · 3 items
[0]
Brain
[1]
-0.1 ± 0.02
[2]
3.52 ± 0.03
[6] array · 1 item
[0]
[7] array · 3 items
[0]
Male
[1]
0.26 ± 0.05
[2]
5.20 ± 0.31
[8] array · 1 item
[0]
[9] array · 3 items
[0]
Female
[1]
0.40 ± 0.06
[2]
5.97 ± 0.38
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section[8]/table-wrap[4]#T5
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Coefficients of the quadratic trends between the kurtosis and skewness of the distribution of the logarithm of gene expression for each of the three data sets.
structure object · 5 fields
pmcid
PMC3002903
section_index
8
section_title
Results
row_count
10
column_count
6
table object · 8 fields
label
Table 5
caption
Coefficients of the quadratic trends between the kurtosis and skewness of the distribution of the logarithm of gene expression for each of the three data sets.
rows array · 10 items
[0] array · 6 items
[0]
Data set
[1]
Constant
[2]
Linear
[3]
Quadratic
[4]
R2
[5]
p-value
[1] array · 6 items
[0]
Craniofacial
[1]
2.96 ± 0.04
[2]
-0.31 ± 0.07
[3]
1.40 ± 0.03
[4]
0.91
[5]
0
[2] array · 1 item
[0]
[3] array · 6 items
[0]
Liver
[1]
3.30 ± 0.07
[2]
0.12 ± 0.10
[3]
1.42 ± 0.06
[4]
0.58
[5]
0
[4] array · 1 item
[0]
[5] array · 6 items
[0]
Brain
[1]
2.97 ± 0.03
[2]
0.03 ± 0.03
[3]
1.31 ± 0.03
[4]
0.65
[5]
0
[6] array · 1 item
[0]
[7] array · 6 items
[0]
Male
[1]
3.65 ± 0.34
[2]
-0.05 ± 0.27
[3]
1.21 ± 0.07
[4]
0.82
[5]
0
[8] array · 1 item
[0]
[9] array · 6 items
[0]
Female
[1]
3.85 ± 0.27
[2]
-0.12 ± 0.20
[3]
1.23 ± 0.05
[4]
0.89
[5]
0
locator
section[8]/table-wrap[4]#T5
[10] object · 16 fields
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asset:table:pmid:21092329:6
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section[8]/table-wrap[5]#T6
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Fraction of null hypotheses rejected by the Chi-square test for the goodness-of-fit to a normal distribution and a mixture of three normal distributions for the "Male" and "Female" data sets
structure object · 5 fields
pmcid
PMC3002903
section_index
8
section_title
Results
row_count
4
column_count
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table object · 8 fields
label
Table 6
caption
Fraction of null hypotheses rejected by the Chi-square test for the goodness-of-fit to a normal distribution and a mixture of three normal distributions for the "Male" and "Female" data sets
rows array · 4 items
[0] array · 3 items
[0]
Data set
[1]
Normal
[2]
3-normal mixture
[1] array · 3 items
[0]
Male
[1]
0.18
[2]
0.17
[2] array · 1 item
[0]
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[0]
Female
[1]
0.16
[2]
0.17
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section[8]/table-wrap[5]#T6
gaps array · 8 items
[0]
asset:data:geo:GSE2814 not downloaded
[1]
asset:data:geo:GSE2814 licence not read
[2]
asset:data:geo:GSE7759 not downloaded
[3]
asset:data:geo:GSE7759 licence not read
[4]
asset:data:geo:GSE8396 not downloaded
[5]
asset:data:geo:GSE8396 licence not read
[6]
asset:data:geo:GSE9444 not downloaded
[7]
asset:data:geo:GSE9444 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
family
correlation_analysis
specific
pearson
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Correlation analysis
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[0]
pearson_r
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data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
band
high
quote
pearson correlation
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id
method-2
family
correlation_analysis
specific
spearman
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Correlation analysis
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[0]
spearman_rho
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
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In this manuscript the results for the AD are provided while those for the KS tests are provided in the Additional material.
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The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30].
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Validation and characterization of DNA microarray gene expression data distribution and associ
[1]
ore than 50% of probe sets on the Affymetrix microarray platform at a 95% confidence level, suggesti
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:21092329", "kind": "science-record", "revision": 8, "content_hash": "sha256:0670468f4a278a86d4875e7c672ed736c00deacf5dda6177480eb2f5fb78850f", "created_at": "2026-11-01T15:14:34Z", "updated_at": "2026-11-01T21:19:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Validation and characterization of DNA microarray gene expression data distribution and associated moments.", "doi": "10.1186/1471-2105-11-576", "pmid": "21092329", "authors": ["Reuben Thomas", "Luis de la Torre", "Xiaoqing Chang", "Sanjay Mehrotra"], "journal": "BMC bioinformatics", "year": 2010, "abstract": "BACKGROUND: The data from DNA microarrays are increasingly being used in order to understand effects of different conditions, exposures or diseases on the modulation of the expression of various genes in a biological system. This knowledge is then further used in order to generate molecular mechanistic hypotheses for an organism when it is exposed to different conditions. Several different methods have been proposed to analyze these data under different distributional assumptions on gene expression. However, the empirical validation of these assumptions is lacking.\nRESULTS: Best fit hypotheses tests, moment-ratio diagrams and relationships between the different moments of the distribution of the gene expression was used to characterize the observed distributions. The data are obtained from the publicly available gene expression database, Gene Expression Omnibus (GEO) to characterize the empirical distributions of gene expressions obtained under varying experimental situations each of which providing relatively large number of samples for hypothesis testing. All data were obtained from either of two microarray platforms--the commercial Affymetrix mouse 430.2 platform and a non-commercial Rosetta/Merck one. The data from each platform were preprocessed in the same manner.\nCONCLUSIONS: The null hypotheses for goodness of fit for all considered univariate theoretical probability distributions (including the Normal distribution) are rejected for more than 50% of probe sets on the Affymetrix microarray platform at a 95% confidence level, suggesting that under the tested conditions a priori assumption of any of these distributions across all probe sets is not valid. The pattern of null hypotheses rejection was different for the data from Rosetta/Merck platform with only around 20% of the probe sets failing the logistic distribution goodness-of-fit test. We find that there are statistically significant (at 95% confidence level based on the F-test for the fitted linear model) relationships between the mean and the logarithm of the coefficient of variation of the distributions of the logarithm of gene expressions. An additional novel statistically significant quadratic relationship between the skewness and kurtosis is identified. Data from both microarray platforms fail to identify with any one of the chosen theoretical probability distributions from an analysis of the l-moment ratio diagram.", "claims": [{"id": "claim-method", "statement": "In this manuscript the results for the AD are provided while those for the KS tests are provided in the Additional material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:21092329", "locator": "sections[5] \"Testing Distributional Assumptions\" paragraph 2", "quote": "In this manuscript the results for the AD are provided while those for the KS tests are provided in the Additional material."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:21092329", "locator": "sections[3] \"Data sets used in the analysis\" paragraph 2", "quote": "The microarray samples used in the analyses in this manuscript were based in part on six separate data sets (see Table 1 and Additional files 1, 2, 3, 4, Table S8, Table S3, Table S1 and Table S2 for better detail of the data in Table 1) obtained from the GEO database [30]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:21092329"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE2814"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE2814"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:21092329", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/1471-2105-11-576", "sha256": 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