Gene Expression-Based High Throughput Screening (GE-HTS) and Application to Leukemia Differentiation
Nature Genetics, Vol. 36, No. 3, 257-263, March 2004.. Published: 2004.02.07
Kimberly Stegmaier, Kenneth N. Ross, Sierra A. Colavito, Shawn O'Malley, Brent R. Stockwell, and Todd R. Golub
Read ManuscriptAbstract
Chemical genomics involves generating large collections of small molecules and using them to modulate cellular states. Although there has been recent progress in the systematic synthesis of structurally diverse compounds, their use in screens of cellular circuitry has remained an ad hoc process. Here, we outline a general, efficient approach called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states, and we describe its application in a particular setting -- the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. The results indicate that GE-HTS may provide a powerful, general approach for chemical screening.
Keywords: AML cancer chemical genomics leukemia small molecule library screen
Supplemental Data
| Description | Link/Filename |
|---|---|
| Text file describing supplemental information contents | README |
| Manuscript | ng1305.pdf |
| Manuscript Figure 1 | Fig1_edited.pdf |
| Manuscript Figure 2 | Fig2_edited.pdf |
| Manuscript Figure 3 | Fig3_edited.pdf |
| Manuscript Figure 4 | Fig4_edited.pdf |
| Manuscript Figure 5 | Fig5_edited.pdf |
| Supplemental Information Document | Stegmaier_SupplementaryMethodsFiguresTables.pdf |
| Supplemental Information Excel Worksheets | Stegmaier_SupplementaryData.xls |
| Initial Myeloid Primary Cell Data | Myeloid_primarycells.res |
| Initial HL-60 Cell Data | HL60_undiff_PMA_ATRA.res |
| Compound Treated HL-60 Cell Data | Myeloid_Screen_Compound_Eval.res |
| Primary Patient APL Cell Data | Myeloid_APL_compound_eval.res |
| Initial Myeloid Primary Cell Data CEL Files | Myeloid_primarycells_CELfiles.tar.gz |
| Initial HL-60 Cell Data CEL Files | HL60_undiff_PMA_ATRA_CELfiles.tar.gz |
| Compound Treated HL-60 Cell Data CEL Files | Myeloid_Screen_Compound_Eval_CELfiles.tar.gz |
| Primary Patient APL Cell Data CEL Files | Myeloid_APL_compound_eval_CELfiles.tar.gz |
| Nature Genetics GE-HTS News and Views | GE-HTS_NandV.pdf |