An empirical bayes adjustment to increase the sensitivity of detecting differentially expressed genes in microarray experiments
MOTIVATION: Detection of differentially expressed genes is one of the major goals of microarray experiments. Pairwise comparison for each gene is not appropriate without controlling the overall (experimentwise) type 1 error rate. Dudoit et al. have advocated use of permutation-based step-down P-value adjustments to correct the observed significance levels for the individual (i.e. for each gene) two sample t-tests.
RESULTS: In this paper, we consider an ANOVA formulation of the gene expression levels corresponding to multiple tissue types. We provide resampling-based step-down adjustments to correct the observed significance levels for the individual ANOVA t-tests for each gene and for each pair of tissue type comparisons. More importantly, we introduce a novel empirical Bayes adjustment to the t-test statistics that can be incorporated into the step-down procedure. Using simulated data, we show that the empirical Bayes adjustment improved the sensitivity of detecting differentially expressed genes up to 16%, while maintaining a high level of specificity. This adjustment also reduces the false non-discovery rate to some degree at the cost of a modest increase in the false discovery rate. We illustrate our approach using a human colon cancer dataset consisting of oligonucleotide arrays of normal, adenoma and carcinoma cells. The number of genes with differential expression level declared statistically significant was about 50 when comparing normal to adenoma cells and about five when comparing adenoma to carcinoma cells. This list includes genes previously known to be associated with colon cancer as well as some novel genes.
AVAILABILITY: R code for the empirical Bayes adjustment and step-down P-value calculation via resampling are available from the supplementary web-site.
SUPPLEMENTARY INFORMATION: http://www.mathstat.gsu.edu/~matsnd/EB/supp.htm.
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2004 |
|---|---|
| Erschienen: |
2004 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
|---|---|
| Enthalten in: |
Bioinformatics (Oxford, England) - 20(2004), 2 vom: 22. Jan., Seite 235-42 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Datta, Susmita [VerfasserIn] |
|---|
| Themen: |
Comparative Study |
|---|
| Anmerkungen: |
Date Completed 03.06.2004 Date Revised 10.12.2019 published: Print Citation Status MEDLINE |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
NLM144409054 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM144409054 | ||
| 003 | DE-627 | ||
| 005 | 20231223033121.0 | ||
| 007 | tu | ||
| 008 | 231223s2004 xx ||||| 00| ||eng c | ||
| 028 | 5 | 2 | |a pubmed24n0482.xml |
| 035 | |a (DE-627)NLM144409054 | ||
| 035 | |a (NLM)14734315 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Datta, Susmita |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An empirical bayes adjustment to increase the sensitivity of detecting differentially expressed genes in microarray experiments |
| 264 | 1 | |c 2004 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 03.06.2004 | ||
| 500 | |a Date Revised 10.12.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a MOTIVATION: Detection of differentially expressed genes is one of the major goals of microarray experiments. Pairwise comparison for each gene is not appropriate without controlling the overall (experimentwise) type 1 error rate. Dudoit et al. have advocated use of permutation-based step-down P-value adjustments to correct the observed significance levels for the individual (i.e. for each gene) two sample t-tests | ||
| 520 | |a RESULTS: In this paper, we consider an ANOVA formulation of the gene expression levels corresponding to multiple tissue types. We provide resampling-based step-down adjustments to correct the observed significance levels for the individual ANOVA t-tests for each gene and for each pair of tissue type comparisons. More importantly, we introduce a novel empirical Bayes adjustment to the t-test statistics that can be incorporated into the step-down procedure. Using simulated data, we show that the empirical Bayes adjustment improved the sensitivity of detecting differentially expressed genes up to 16%, while maintaining a high level of specificity. This adjustment also reduces the false non-discovery rate to some degree at the cost of a modest increase in the false discovery rate. We illustrate our approach using a human colon cancer dataset consisting of oligonucleotide arrays of normal, adenoma and carcinoma cells. The number of genes with differential expression level declared statistically significant was about 50 when comparing normal to adenoma cells and about five when comparing adenoma to carcinoma cells. This list includes genes previously known to be associated with colon cancer as well as some novel genes | ||
| 520 | |a AVAILABILITY: R code for the empirical Bayes adjustment and step-down P-value calculation via resampling are available from the supplementary web-site | ||
| 520 | |a SUPPLEMENTARY INFORMATION: http://www.mathstat.gsu.edu/~matsnd/EB/supp.htm | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Evaluation Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, P.H.S. | |
| 650 | 4 | |a Validation Study | |
| 700 | 1 | |a Satten, Glen A |e verfasserin |4 aut | |
| 700 | 1 | |a Benos, Dale J |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Jiazeng |e verfasserin |4 aut | |
| 700 | 1 | |a Heslin, Martin J |e verfasserin |4 aut | |
| 700 | 1 | |a Datta, Somnath |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioinformatics (Oxford, England) |d 1998 |g 20(2004), 2 vom: 22. Jan., Seite 235-42 |w (DE-627)NLM094620342 |x 1367-4811 |7 nnns |
| 773 | 1 | 8 | |g volume:20 |g year:2004 |g number:2 |g day:22 |g month:01 |g pages:235-42 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 20 |j 2004 |e 2 |b 22 |c 01 |h 235-42 | ||