Home LiteratureArticle Details
PMID: 11435405 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

An efficient and robust statistical modeling approach to discover differentially expressed genes using genomic expression profiles.

Genome research ·Vol. 11 ·No. 7 ·2001-07-00 ·Pages 1227-36

Thomas JG, Olson JM, Tapscott SJ, Zhao LP

Abstract

We have developed a statistical regression modeling approach to discover genes that are differentially expressed between two predefined sample groups in DNA microarray experiments. Our model is based on well-defined assumptions, uses rigorous and well-characterized statistical measures, and accounts for the heterogeneity and genomic complexity of the data. In contrast to cluster analysis, which attempts to define groups of genes and/or samples that share common overall expression profiles, our modeling approach uses known sample group membership to focus on expression profiles of individual genes in a sensitive and robust manner. Further, this approach can be used to test statistical hypotheses about gene expression. To demonstrate this methodology, we compared the expression profiles of 11 acute myeloid leukemia (AML) and 27 acute lymphoblastic leukemia (ALL) samples from a previous study (Golub et al. 1999) and found 141 genes differentially expressed between AML and ALL with a 1% significance at the genomic level. Using this modeling approach to compare different sample groups within the AML samples, we identified a group of genes whose expression profiles correlated with that of thrombopoietin and found that genes whose expression associated with AML treatment outcome lie in recurrent chromosomal locations. Our results are compared with those obtained using t-tests or Wilcoxon rank sum statistics.

MeSH Terms
Acute Disease Gene Expression Profiling/methods,statistics & numerical data Gene Expression Regulation, Neoplastic/genetics Humans Leukemia, Myeloid/genetics Models, Genetic Models, Statistical Oligonucleotide Array Sequence Analysis/methods,statistics & numerical data Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics Regression Analysis
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Thomas J G
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Olson J M
Tapscott S J
Zhao L P
References (77)
77 references, click to expand
  1. Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations.
    Blood. 1995 Oct 15;86(8):2906-12 PMID: 7579382
  2. Microtubule changes in hematologic malignant cells treated with paclitaxel and comparison with vincristine cytotoxicity.
    Blood Cells Mol Dis. 1995;21(2):119-30 PMID: 8846041
  3. The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A.
    J Biol Chem. 1996 May 10;271(19):11059-62 PMID: 8626647
  4. Loss of the chromosomal region 5q11-q31 in the myeloid cell line HL-60: characterization by comparative genomic hybridization and fluorescence in situ hybridization.
    Genes Chromosomes Cancer. 1996 Mar;15(3):182-6 PMID: 8721684
  5. Growth stimulatory effect of thrombopoietin on the blast cells of acute myelogenous leukaemia.
    Br J Haematol. 1996 Sep;94(3):513-6 PMID: 8790152
  6. Duplication of 2q31-qter as a sole aberration in a case of non-Hodgkin's lymphoma.
    Cancer Genet Cytogenet. 1996 Sep;90(2):102-5 PMID: 8830716
  7. The Sp-family of transcription factors.
    Gene. 1999 Oct 1;238(2):291-300 PMID: 10570957
  8. Clustering gene expression patterns.
    J Comput Biol. 1999 Fall-Winter;6(3-4):281-97 PMID: 10582567
  9. Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias.
    Leukemia. 1999 Dec;13(12):1993-9 PMID: 10602420
  10. Thrombospondin-2: a potent endogenous inhibitor of tumor growth and angiogenesis.
    Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14888-93 PMID: 10611308
  11. Genomic biology.
    Cell. 2000 Jan 7;100(1):169-83 PMID: 10647941
  12. Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells.
    Blood. 2000 Feb 15;95(4):1420-6 PMID: 10666220
  13. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.
    Nature. 2000 Feb 3;403(6769):503-11 PMID: 10676951
  14. Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21).
    Genes Chromosomes Cancer. 2000 Mar;27(3):229-38 PMID: 10679911
  15. Making the most of microarray data.
    Nat Genet. 2000 Mar;24(3):204-6 PMID: 10700163
  16. Use of dual-color interphase FISH for the detection of inv(16) in acute myeloid leukemia at diagnosis, relapse and during follow-up: a study of 23 patients.
    Leukemia. 2000 Mar;14(3):364-8 PMID: 10720127
  17. Molecular genetics in acute leukemia.
    Leukemia. 2000 Mar;14(3):513-7 PMID: 10720153
  18. Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3260-5 PMID: 10737792
  19. Effect of thrombopoietin on proliferation of blasts from patients with myelodysplastic syndromes.
    Stem Cells. 2000;18(2):112-9 PMID: 10742383
  20. Thrombopoietin increases platelet sensitivity to alpha-thrombin via activation of the ERK2-cPLA2 pathway.
    Thromb Haemost. 2000 Apr;83(4):610-6 PMID: 10780326
  21. Thioredoxin reductase, a redox-active selenoprotein, is secreted by normal and neoplastic cells: presence in human plasma.
    Cancer Res. 2000 Apr 15;60(8):2281-9 PMID: 10786696
  22. Notch signalling via RBP-J promotes myeloid differentiation.
    EMBO J. 2000 Jun 1;19(11):2558-68 PMID: 10835354
  23. Molecular characterization of a complex chromosomal translocation breakpoint t(10;14) including the HOX11 oncogene locus.
    Leukemia. 1999 Jun;13(6):975-9 PMID: 10360388
  24. Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays.
    Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6745-50 PMID: 10359783
  25. Purified photoproducts of merocyanine 540 trigger cytochrome C release and caspase 8-dependent apoptosis in human leukemia and melanoma cells.
    Blood. 1999 Jun 15;93(12):4096-108 PMID: 10361106
  26. Mpl ligand enhances the transcription of the cyclin D3 gene: a potential role for Sp1 transcription factor.
    Blood. 1999 Jun 15;93(12):4208-21 PMID: 10361118
  27. Thrombopoietin and hematopoietic stem cell development.
    Ann N Y Acad Sci. 1999 Apr 30;872:314-9 PMID: 10372133
  28. Constitutive expression of the Wilms' tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF).
    Leuk Res. 1999 May;23(5):499-505 PMID: 10374864
  29. Isochromosome 17q in blast crisis of chronic myeloid leukemia and in other hematologic malignancies is the result of clustered breakpoints in 17p11 and is not associated with coding TP53 mutations.
    Blood. 1999 Jul 1;94(1):225-32 PMID: 10381517
  30. Systematic determination of genetic network architecture.
    Nat Genet. 1999 Jul;22(3):281-5 PMID: 10391217
  31. Systematic changes in gene expression patterns following adaptive evolution in yeast.
    Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9721-6 PMID: 10449761
  32. 3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: biological and clinical features.
    Haematologica. 1999 Aug;84(8):690-4 PMID: 10457403
  33. Regulation of megakaryocytopoiesis.
    Haemostasis. 1999 Sep;29(1):27-40 PMID: 10494032
  34. Identification of novel chromosomal rearrangements in acute myelogenous leukemia involving loci on chromosome 2p23, 15q22 and 17q21.
    Leukemia. 1999 Oct;13(10):1534-8 PMID: 10516754
  35. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.
    Science. 1999 Oct 15;286(5439):531-7 PMID: 10521349
  36. Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.
    Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9127-32 PMID: 10922068
  37. Global gene expression profiling in Escherichia coli K12. The effects of integration host factor.
    J Biol Chem. 2000 Sep 22;275(38):29672-84 PMID: 10871608
  38. Translocation X;10 in a case of congenital acute monocytic leukemia.
    Cancer Genet Cytogenet. 1985 Apr 15;16(4):357-64 PMID: 3856472
  39. The most common chromosome change in 86 chronic B cell or T cell tumors: a 14q32 translocation.
    Cancer Genet Cytogenet. 1986 Jan 15;19(3-4):219-27 PMID: 3484667
  40. A new translocation t(1;4;11) in congenital acute nonlymphocytic leukemia (acute myeloblastic leukemia).
    Hum Genet. 1987 May;76(1):106-8 PMID: 3471701
  41. Ring chromosome in a case of acute myelomonocytic leukemia: its significance and a review of the literature.
    Hematol Pathol. 1987;1(1):57-65 PMID: 3332873
  42. Clustering of breakpoints on chromosome 10 in acute T-cell leukemias with the t(10;14) chromosome translocation.
    Proc Natl Acad Sci U S A. 1989 Jun;86(11):4161-5 PMID: 2542965
  43. Estimating equations for parameters in means and covariances of multivariate discrete and continuous responses.
    Biometrics. 1991 Sep;47(3):825-39 PMID: 1742441
  44. Cytogenetic studies in acute promyelocytic leukemia: a survey of secondary chromosomal abnormalities.
    Genes Chromosomes Cancer. 1991 Sep;3(5):332-7 PMID: 1797083
  45. Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene.
    Mol Cell Biol. 1992 Aug;12(8):3346-55 PMID: 1630450
  46. Mechanisms underlying abnormal trafficking of malignant progenitors in chronic myelogenous leukemia. Decreased adhesion to stroma and fibronectin but increased adhesion to the basement membrane components laminin and collagen type IV.
    J Clin Invest. 1992 Oct;90(4):1232-41 PMID: 1383271
  47. Recurrent cytogenetic abnormalities observed in complete remission of acute myeloid leukemia do not necessarily mark preleukemic cells.
    Leukemia. 1994 Feb;8(2):245-9 PMID: 8309249
  48. Molecular cloning and expression of a cDNA encoding NGAL: a lipocalin expressed in human neutrophils.
    Biochem Biophys Res Commun. 1994 Aug 15;202(3):1468-75 PMID: 8060329
  49. Molecular characterization of 16p deletions associated with inversion 16 defines the critical fusion for leukemogenesis.
    Blood. 1995 Feb 1;85(3):772-9 PMID: 7833479
  50. Carboxypeptidase M is identical to the MAX.1 antigen and its expression is associated with monocyte to macrophage differentiation.
    J Biol Chem. 1995 Jun 30;270(26):15644-9 PMID: 7797563
  51. Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin.
    Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):6132-6 PMID: 7597091
  52. Expression of thrombopoietin and thrombopoietin receptor MPL in human leukemia-lymphoma and solid tumor cell lines.
    Leuk Res. 1996 Oct;20(10):831-8 PMID: 8960108
  53. [Oncogenesis of T-cell prolymphocytic leukemia].
    Pathol Biol (Paris). 1996 Oct;44(8):689-93 PMID: 8977926
  54. Thrombospondin, a negative modulator of megakaryocytopoiesis.
    J Lab Clin Med. 1997 Feb;129(2):231-8 PMID: 9016860
  55. AICL: a new activation-induced antigen encoded by the human NK gene complex.
    Immunogenetics. 1997;45(5):295-300 PMID: 9038101
  56. Sorting of the specific granule protein, NGAL, during granulocytic maturation of HL-60 cells.
    Blood. 1997 Mar 15;89(6):2113-21 PMID: 9058734
  57. 5q-, twenty-five years later: a synopsis.
    Cancer Genet Cytogenet. 1997 Mar;94(1):1-7 PMID: 9078284
  58. Variant complex translocations involving chromosomes 1, 9, 9, 15 and 17 in acute promyelocytic leukemia without RAR alpha/PML gene fusion rearrangement.
    Leukemia. 1997 Apr;11(4):514-8 PMID: 9096691
  59. Thrombin cleaves recombinant human thrombopoietin: one of the proteolytic events that generates truncated forms of thrombopoietin.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4669-74 PMID: 9114049
  60. Inactivation of cyclin-dependent kinase inhibitor genes and development of human acute leukemias.
    Leuk Lymphoma. 1997 Mar;25(1-2):23-35 PMID: 9130611
  61. Chromosomal breakpoints and changes in DNA copy number in refractory acute myeloid leukemia.
    Leukemia. 1997 Jul;11(7):958-63 PMID: 9204975
  62. Constitutional inversion of chromosome 7 and hematologic cancers.
    Cancer Genet Cytogenet. 1997 Jul 1;96(1):46-9 PMID: 9209470
  63. Exploring the metabolic and genetic control of gene expression on a genomic scale.
    Science. 1997 Oct 24;278(5338):680-6 PMID: 9381177
  64. Characterization of cryptic rearrangements and variant translocations in acute promyelocytic leukemia.
    Blood. 1997 Dec 15;90(12):4876-85 PMID: 9389704
  65. Yeast microarrays for genome wide parallel genetic and gene expression analysis.
    Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13057-62 PMID: 9371799
  66. Characterization of a t(10;12)(q24;p13) in a case of CML in transformation.
    Genes Chromosomes Cancer. 1997 Dec;20(4):408-11 PMID: 9408758
  67. Genome-wide expression monitoring in Saccharomyces cerevisiae.
    Nat Biotechnol. 1997 Dec;15(13):1359-67 PMID: 9415887
  68. Thrombopoietin and erythropoietin activate inside-out signaling of integrin and enhance adhesion to immobilized fibronectin in human growth-factor-dependent hematopoietic cells.
    Ann Hematol. 1997 Nov-Dec;75(5-6):207-13 PMID: 9433377
  69. Induction of thrombospondin-1 by all-trans retinoic acid modulates growth and differentiation of HL-60 myeloid leukemia cells.
    Leukemia. 1997 Dec;11(12):2137-42 PMID: 9447832
  70. Thrombopoietin activates human platelets and induces tyrosine phosphorylation of p80/85 cortactin.
    Thromb Haemost. 1998 Jan;79(1):195-201 PMID: 9459347
  71. Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors.
    EMBO J. 1998 Oct 1;17(19):5744-56 PMID: 9755174
  72. The transcriptional program of sporulation in budding yeast.
    Science. 1998 Oct 23;282(5389):699-705 PMID: 9784122
  73. EHT, a new member of the MTG8/ETO gene family, maps on 20q11 region and is deleted in acute myeloid leukemias.
    Blood. 1998 Nov 1;92(9):3481-4 PMID: 9787195
  74. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization.
    Mol Biol Cell. 1998 Dec;9(12):3273-97 PMID: 9843569
  75. Cluster analysis and display of genome-wide expression patterns.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8 PMID: 9843981
  76. Cloning of the murine beta5 integrin subunit promoter. Identification of a novel sequence mediating granulocyte-macrophage colony-stimulating factor-dependent repression of beta5 integrin gene transcription.
    J Biol Chem. 1999 Jan 15;274(3):1366-74 PMID: 9880508
  77. Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation.
    Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2907-12 PMID: 10077610
Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.165101
Published
2001-07-00
Pages
1227-36
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC311075
Subset
IM
Grants
NCI NIH HHS · P01 CA053996 · United States
NCI NIH HHS · CA53996 · United States
NIGMS NIH HHS · GM58897 · United States
NHGRI NIH HHS · HG02283 · United States
External Links
PubMed source DOI: 10.1101/gr.165101 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2