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PubMed2004

Annealing control primer system for identification of differentially expressed genes on agarose gels.

We developed GeneFishing technology, an improved method for the identification of differentially expressed genes (DEGs) using our novel annealing control primer (ACP) system. Because of high annealing specificity during PCR using the ACP system, the application of the ACP to DEG discovery generates reproducible, authentic, and long (100 bp to 2 kb) PCR products that are detectable on agarose gels. To demonstrate this method for gene expression profiling, Gene-Fishing technology was used to detect genes that are differentially expressed during development using total RNAs isolated from mouse conceptus tissues at 4.5-18.5 days of gestation. Ten DEGs (DEG1-10) were isolated and confirmed by Northern blot hybridization. The sequence analysis of these DEGs showed that DEG6 and DEG10 are unknown genes.

Animals↗
PubMed1988

Differential expression of the Na,K-ATPase alpha 1 and alpha 2 subunit genes in a murine myogenic cell line. Induction of the alpha 2 isozyme during myocyte differentiation.

Expression of Na,K-ATPase catalytic alpha isoform (alpha 1, alpha 2, and alpha 3) and beta subunit genes in rodent muscle was investigated using the murine C2C12 myogenic cell line. RNA blot analyses of myoblasts revealed expression primarily of the alpha 1 mRNA and low levels of alpha 2 mRNA. Fusion of the proliferating myoblasts to form myotubes was accompanied by an approximate 12-fold induction of the alpha 2 mRNA. In contrast, expression of alpha 1 mRNA remained constant throughout myogenesis. The alpha 3 mRNA was not detected in either myoblasts or myotubes. The beta mRNA abundance also increased 2-3-fold during myotube formation. In rodent tissues, low and high affinity cardiac glycoside (e.g. ouabain) receptors have been shown to be associated with the Na,K-ATPase catalytic alpha 1 and alpha 2 isoform subunits, respectively. The existence of these two functional classes of Na,K-ATPase in myoblasts and myotubes correlated with the biphasic ouabain inhibition of Na,K-ATPase activity. Confluent myoblasts expressed primarily the alpha 1 isozyme (IC50 = 3.6 X 10(-5) M; 95% of total activity) and lesser amounts of the alpha 2 isozyme (IC50 = 1.1 X 10(-7) M; 5% of total activity). In contrast, the myotubes showed significant levels of the alpha 1 isozyme (IC50 = 4.0 X 10(-5) M; 68% of total activity) and, in addition, showed a 6-fold increase in the relative levels of the alpha 2 isozyme (IC50 = 1.1 X 10(-7) M; 32% of total activity). To quantitate further the expression of the high affinity, ouabain-sensitive alpha 2 isozyme, a whole cell [3H]ouabain-binding assay was used. Results revealed that myotubes have an approximately 6-fold greater concentration of [3H]ouabain-binding sites than myoblasts with an apparent dissociation constant (Kd) of 1.4 X 10(-7) M. The results indicate that muscle cells can express multiple isozymes of Na,K-ATPase and that expression of the alpha 2 isozyme is developmentally regulated during myogenesis.

Animals↗
PubMed1998

Differential expression pattern of the three Fringe genes is associated with epidermal differentiation.

Epidermal differentiation, as keratinocytes go through different layers to the skin surface, may imply a differential activation of Notch transmembrane proteins. In mouse, as recently shown in Drosophila, Notch activation by its ligands may be modulated by Fringe secreted proteins. Therefore, we cloned the mouse homolog of Radical-fng, synthesized riboprobes for Lunatic-fng, Manic-fng, and Radical-fng, and examined their expression during epidermal differentiation. Expression of all three genes is differentially activated during embryonic epidermal stratification. Manic-fng and Lunatic-fng are expressed in the basal layer, whereas Lunatic-fng is expressed in the granular layer and Radical-fng is restricted to the most differentiated nucleated layer. This expression decreases by a few days postnatally and can be reactivated by retinoic acid treatment, which triggers a new distribution of Fringe transcripts and a thickening of the granular layer. Therefore, Manic, Lunatic, and Radical Fringe by modulating the Notch pathway may play a key role in defining the different steps of keratinocyte differentiation.

Animals↗
PubMed2001

Differential expression of growth factors in irradiated mouse testes.

PURPOSE: By using as an experimental model the male mouse gonad, which contains both radiosensitive (germ) and radioresistant (somatic) cells, we have studied the growth factor (and/or receptor) expression of transforming growth factor-beta receptor (TGFbeta RI), stem cell factor (SCF), c-kit, Fas-L, Fas, tumor necrosis factor receptor (TNF R55), and leukemia inhibiting factor receptor (LIF-R) after local irradiation. METHODS AND MATERIALS: Adult male mice were locally irradiated on the testes. Induction of apoptosis in the different testicular cell types following X-ray radiation was identified by the TdT-mediated dUTP Nick End Labeling (TUNEL) approach. Growth factor expression was evidenced by semiquantitative RT-PCR and Western blot analyses. RESULTS: Apoptosis, identified through the TUNEL approach, occurred in radiosensitive testicular (premeotic) germ cells with the following kinetics: the number of apoptotic cells increased after 24 h (p < 0.001) and was maximal 48 h after a 2-Gy ionizing radiation (p < 0.001). Apoptotic cells were no longer observed 72 h after a 2-Gy irradiation. The number of apoptotic cells increased with the dose of irradiation (1-4 Gy). In the seminiferous tubules, the growth factor expression in premeiotic radiosensitive germ cells was modulated by irradiation. Indeed Fas, c-kit, and LIF-R expression, which occurs in (radiosensitive) germ cells, decreased 24 h after a 2-Gy irradiation, and the maximal decrease was observed with a 4-Gy irradiation. The decrease in Stra8 expression occurred earlier, at 4 h after a 2-Gy irradiation. In addition, a significant (p < 0.03) decrease in Stra8 mRNA levels was observed at the lowest dose used (0.5 Gy, 48 h). Moreover, concerning a growth factor receptor, such as TGFbeta RI, which is expressed both in radiosensitive and radioresistant cells, we observed a differential expression depending on the cell radiosensitivity after irradiation. Indeed, TGFbeta RI expression was increased after irradiation in interstitial radioresistant testicular cells in a dose- and time-dependent manner, while it decreased in seminiferous radiosensitive (germ cells) testicular cells. Such a differential expression between radioresistant and radiosensitive cells in TGFbeta RI levels was observed in terms of both mRNA and protein. In contrast, the growth factors specifically expressed in the somatic radioresistant (Sertoli) cells in the seminiferous tubules (SCF, Fas-L, TNF R55) were not affected by ionizing radiation (up to 4 Gy, 72 h). CONCLUSION: Growth factor expression decreased in the radiosensitive testicular cells after irradiation. Such a decrease occurred before the detection of apoptosis using the TUNEL approach. TGFbeta RI mRNA levels decreased in the radiosensitive cells, whereas it increased in the radioresistant cells, suggesting that TGFbeta RI may represent a biomarker of the intrinsic radiosensitivity of cells.

Animals↗
PubMed2000

Identification of differentially expressed genes by mutually subtracted RNA fingerprinting.

A mutually subtracted RNA fingerprinting (SuRF) method has been developed that allows efficient identification of differentially expressed sequence tags between two samples. Mutual subtractions of two RNA samples are achieved by first synthesizing cDNAs using oligo(dT) coupled with magnetic beads which are then reciprocally hybridized to starting RNA samples to remove common mRNAs between them. The second step involves differential fingerprinting of the subtracted RNA samples by polymerase chain reaction with specially designed degenerate primers. SuRF was applied to identify alteration in gene expression pertinent to osteogenic sarcoma which was achieved by employing the method between FOB (an immortalized fetal osteoblast) and MG63 (an osteosarcoma) cell lines. An estimated 10% of the total expressed genes in these two cell types were screened by the method. This analysis identified 96 differentially expressed sequences, none of which was identified repeatedly. A subset of these sequences was subsequently confirmed to have differential expression between the two cell types. Removal of common mRNAs prior to differential display should diminish redundant identification of abundant genes and increase the chance of identifying rare differentially expressed genes.

DNA, Complementary↗
PubMed2001

ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system.

The neuregulin (NRG) family of growth and differentiation factors and their erbB receptors contribute importantly to the development of the nervous system, but their distribution and function in the adult brain are poorly understood. The present study showed that erbB2, erbB3, and erbB4 transcripts and protein are distributed throughout all areas of adult rat brain. These three receptors were differentially expressed in neurons and glia. Some neurons expressed only a subset of erbB kinases, whereas other neurons expressed all three erbB receptors but sequestered each of these polypeptides into distinct cellular compartments. In synapse-rich regions, erbB immunoreactivity appeared as punctate-, axon-, and/or dendrite-associated staining, suggesting that NRGs are involved in the formation and maintenance of synapses in adult brain. ErbB labeling also was present in neuronal soma, indicating that NRGs act at sites in addition to the synapse. Glia in adult brain also differentially expressed erbB3 and erbB4. Approximately half of the erbB3 labeling in white matter was associated with S100beta+/glial fibrillary acidic protein negative macroglia (i.e., oligodendrocytes or glial fibrillary acidic protein negative astrocytes). In contrast, macroglia in gray matter did not express erbB3. The remaining erbB3 immunoreactivity in white matter and erbB4 glial staining seemed to be associated with microglia. These results showed that erbB receptors are expressed widely in adult rat brain and that each erbB receptor subtype has a distinct distribution. The differential distributions of erbB receptors in neurons and glia and the known functional differences between these kinases suggest that NRGs have distinct effects on these cells. The continued expression of NRGs and their erbB receptors in mature brain also implies that these molecules perform important functions in the brain throughout life.

Age Factors↗
PubMed2006

Identification of differentially expressed genes in HPV-positive and HPV-negative oropharyngeal squamous cell carcinomas.

Human papillomaviruses (HPVs) have been implicated in the pathogenesis of a subset of squamous cell carcinoma of the head and neck (SCCHN). The goal of this study was to compare the cellular gene expression profiles of HPV-positive and HPV-negative oropharyngeal carcinomas with those of the normal oral epithelium. Using Affymetrix Human U133A GeneChip, our results showed that 397 genes were differentially expressed in HPV-positive SCCHN compared to the normal oral epithelium. The upregulated genes included those involved in cell cycle regulation (CDKN2A), cell differentiation (SFRP4) and DNA repair (RAD51AP1), while the downregulated genes included those involved in proteolysis (PRSS3). We also found 162 differentially expressed genes in HPV-negative SCCHN compared to the normal oral mucosa. The upregulated genes included those involved in cell proliferation (AKR1C3) and transcription regulation (SNAPC1), while downregulated genes included those involved in apoptosis (CLU) and RNA processing (RBM3). Our studies also identified a subgroup of 59 differentially expressed genes in HPV-positive SCCHN as compared to both HPV-negative SCCHN and normal oral tissues. Such upregulated genes included those involved in nuclear structure and meiosis (SYCP2), DNA repair (RFC5), and transcription regulation (ZNF238). Genes involved in proteolysis (KLK8) and signal transduction (CRABP2) were found to be downregulated in HPV-positive SCCHN. The results of GeneChip experiments were validated by quantitative real-time RT-PCR analysis of a few representative genes. Our results reveal specific gene expression patterns in HPV-positive and HPV-negative oropharyngeal squamous carcinomas that may serve as potential biomarkers for the development of SCCHN.

Carcinoma, Squamous Cell↗
PubMed2001

Differentially expressed DNA sequences following recovery from unilateral testicular torsion in rat.

The molecular response during recovery from torsion-induced stress in the testis is diverse with a variety of mechanisms. In this study, using unilateral testicular torsion in rat as a model, we used subtractive hybridisation to identify differentially expressed DNA sequences in the torsioned and control testes. Three genes were identified as being down regulated in the torsioned testis compared with controls: Control Testis genes 1, 2 and 3 (CT1, CT2 and CT3). Two genes were up regulated in the torsioned testes: Torsioned Testes genes 1 and 2 (TT1 and TT2). Differential expression was confirmed by Reverse Northern blot analysis. An homology search revealed that CT1 had 88% homology with rat metallothionein cDNA; CT2 had 81% homology with rat cell surface antigen in MHC class I, but no homology could be found for CT3. TT1 had 92% identity with rat Rieske iron-sulphur protein mRNA whereas TT2 had 73% identity with a human clone of unknown function (RP 11-252D22). These results indicate that changes in gene expression occur following torsion induced stress, and that identification of differentially expressed genes may provide insights into the mechanisms of cellular tissue damage in this model.

Animals↗
PubMed2001

Differential expression of potato U1A spliceosomal protein genes: a rapid method for expression profiling of multigene families.

The spliceosomal protein, UIA, is a component of the U1snRNP essential to pre-mRNA splicing. From the ubiquitous nature of the splicing machinery, expression of U1A genes is expected to be constitutive. However, many plant genes are organised in multigene families that exhibit variation in expression profiles. Without detailed knowledge of the size of the U1A gene family or their degree of sequence variation, we examined the expression of the U1A genes using a novel approach. The approach was based on 5' RACE with [32P]-labelled primers and separation of products on high-resolution DNA sequencing gels to give a 'snapshot' of the expression of U1A genes. This was followed by sequencing of cloned 5' RACE products and of products re-amplified from excised bands. In combination with RT-PCR/SSCP, these analyses allowed the rapid identification of different gene transcripts and assessment of their relative expression profiles. Transcripts from four U1A genes (U1A-1 to U1A-4) were identified, of which U1A-1 and U1A-2 were expressed much more highly than U1A-3 and U1A-4. Differential expression of the two most highly expressed genes, U1A-1 and UIA-2, was observed in that only U1A-2 was expressed in flowers. Upstream sequences of U1A-1 and U1A-2 were cloned and the gene-specific promoters identified on the basis of the sequence variation defined from the 5' RACE products. The differential expression of these genes may be due to a 1.3 kb insertion less than 200 bp upstream of the U1A-1 coding sequence. This approach can be used more generally to examine expression profiles of multigene families, and in particular to refine information from EST or microarray analyses, and to isolate rapidly gene-specific promoters.

Base Sequence↗
PubMed1998

Differential subtraction display: a unified approach for isolation of cDNAs from differentially expressed genes.

We have developed a novel efficient approach, termed differential subtraction display, for the identification of differentially expressed genes. Several critical parameters for the reproducibility and enhanced sensitivity of display, as well as steps to reduce the number of false positive cDNA species, have been defined. These include- (a) use of standardized oligo(dT)-primed cDNA pools rather than total RNA as the starting material for differential display, (b) critical role of optimal cDNA input for each distinct class of primers, (c) phenomena of primer dominance and interference, and (d) design of a novel set of enhanced specificity anchor primers. Introduction of an efficient subtractive hybridization step prior to cloning of cDNA species enriches the bona fide cDNA species that are either exclusively present in one sample (+/-) or show altered expression (up-/down-regulation) in RNA samples from two different tissues or cell types. This approach, in comparison to differential display, has several advantages in terms of reproducibility and enhanced sensitivity of display coupled to the cloning of enriched bona fide cDNA species corresponding to differentially expressed RNAs.

Animals↗
PubMed1998

Differential expression of insulin-like growth factor binding proteins in high versus low Gleason score prostate cancer.

PURPOSE: The insulin-like growth factor (IGF) system appears to be important in human prostate cancer biology. Expression of specific IGF binding proteins (IGFBPs) by prostate cancer tissues may modulate IGF cellular actions, and possibly determine both IGF-dependent tumor growth and biological aggressiveness in vivo. The purpose of this study was to examine the differential expression of all six IGFBP genes in benign and malignant prostate tissue samples. MATERIALS AND METHODS: Using RNAse protection assays, we examined expression of IGFBPs 1 through 6 in 23 paired benign and neoplastic prostate tissue samples obtained from the same prostatectomy specimen. RNA expression levels on each tissue sample were determined densitometrically and groups compared using standard Student's t test. RESULTS: We found expression of IGFBPs 2 through 6, but not IGFBP-1, in both malignant and benign tissues. A statistically significant differential expression of IGFBPs 2, 3 and 5 was found between tumors with high Gleason score and those with low scores and benign tissues. Expression of IGFBPs 2 and 5 was higher (p = 0.002 and 0.04, respectively) while that of IGFBP-3 was lower (p = 0.05) in high versus low Gleason score cancer specimens. Expression of IGFBPs 4 and 6 was no different between tumors (p = 0.052 and 0.25, respectively). No significant differences in IGFBP expression were evident between benign and tumor tissues when tumor grade was not considered. CONCLUSION: Our results indicate that differential expression of certain IGFBPs in human prostate cancer correlates with tumor Gleason score. Thus, expression of certain IGFBPs in prostate cancer may be used as a surrogate marker of aggressive clinical behavior.

Gene Expression Regulation, Neoplastic↗
PubMed1995

Identification of differentially expressed Leishmania donovani genes using arbitrarily primed polymerase chain reactions.

Arbitrarily primed polymerase chain reactions (AP-PCR) were used to amplify polymorphic DNA fragments from the genomes of a variety of geographic isolates of Leishmania donovani (Ld). From the latter, five polymorphic DNA fragments were cloned and sequence analysis identified 15 unique clones. Northern blot analysis showed that 13 of the 15 clones hybridized to transcribed RNAs isolated from Ld. Eight of these 13 AP-PCR clones specifically hybridized to Ld RNAs that were differentially expressed in promastigote and 'amastigote' cells. Comparative Northern analysis of four differentially expressed AP-PCR clones indicated that two clones, LdS-14-14 and LdI-9-7, were expressed in Ld and several other Leishmania species. However, RNAs corresponding to two other AP-PCR clones, LdE-6-1 and LdI-9-5, were detected only in members of the Ld complex, and not in L. major (Lm) or L. tropica (Lt). Comparative Southern blot analysis of the LdS-14-14 locus revealed numerous restriction-fragment length polymorphisms (RFLP) distinguishing Lm and Lt from the Ld isolates and L. infantum. However, the LdS-14-14 loci were mapped to similar-sized chromosomes observed among all Old World Leishmania species tested, indicating that localized nucleotide divergence, not chromosomal rearrangement, was responsible for altered Southern blot patterns. These results demonstrate that AP-PCR is a very useful method for identifying expressed gene sequences in organisms of relatively low-complexity genomes. Interestingly, the majority of these sequences identified in this study correspond to differentially expressed genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Investigation of differentially expressed genes during the development of mouse cerebellum.

Before the discovery of DNA microarray and DNA chip technology, the expression of only a small number of genes could be analyzed at a time. Currently, such technology allows us the simultaneous analysis of a large number of genes to systematically monitor their expression patterns that may be associated with various biological phenomena. We utilized the Affymetrix GeneChip Mu11K to analyze the gene expression profile in developing mouse cerebellum to assist in the understanding of the genetic basis of cerebellar development in mice. Our analysis showed 81.6% (10,321/12,654) of the genes represented on the GeneChip were expressed in the postnatal cerebellum, and among those, 8.7% (897/10,321) were differentially expressed with more than a two-fold change in their maximum and minimum expression levels during the developmental time course. Further analysis of the differentially expressed genes that were clustered in terms of their expression patterns and the function of their encoded products revealed an aspect of the genetic foundation that lies beneath the cellular events and neural network formation that takes place during the development of the mouse cerebellum.

Journal Article↗
PubMedDate not supplied

Differential expression of critical cellular genes in human lung adenocarcinomas and squamous cell carcinomas in comparison to normal lung tissues.

The Atlas human cDNA expression array was used to evaluate gene expression profile changes in the genesis of human lung adenocarcinomas and squamous cell carcinomas. Gene expression changes between adenocarcinomas and squamous cell carcinomas were also analyzed. Of the 588 gene targets, 262 genes were expressed in these tissues and, of these, 45 genes were differentially expressed by at least two-fold in tumor tissues compared to corresponding normal tissues. Semiquantitative reverse-transcriptase polymerase chain reaction was used to confirm gene expression changes. Only those genes that reflected changes in >50% of the analyzed tissues were included in the final analysis. Ultimately, 26 genes were evaluated with 14 genes overexpressed and 12 genes underexpressed compared to matching normal lung tissues. Although similar expression changes were detected in adenocarcinomas and squamous cell carcinomas for most of the genes analyzed, some subtype-specific differences were also found. Genes encoding cell cycle regulators, intracellular signal transducers, cell receptor and adhesion molecules, growth factors, oncogenes, and apoptotic effectors were differentially expressed in this study. These gene expression changes may directly contribute to the initiation or progression of human lung cancer or may be secondary effects of the tumorigenesis process. Regardless, many of these differences may be useful in the diagnosis and/or treatment of this deadly disease.

Adenocarcinoma↗
PubMed2005

Fold-change estimation of differentially expressed genes using mixture mixed-model.

Microarray experiments produce expression measurements for thousands of genes simultaneously, though usually for a small number of RNA samples. The most common problem is the identification of genes that are differentially expressed between different groups of samples or biological conditions. As the number of genes far exceeds the number of RNA samples, the inherent multiplicity poses a severe problem in both hypothesis testing and effect estimation. While much of the recent literature is focused on the hypothesis aspects, we concentrate in this paper on effect estimation as a tool for the identification of differentially expressed genes. We propose a linear mixed model where the random effects are assumed to follow a mixture distribution, and study in detail the case of three normals, corresponding to genes that are down-, up- or non regulated. Our approach leads to a new type of non-linear shrinkage estimation, where a proportion of estimates is shrunk to zero, while the rest follows standard linear shrinkage. This allows us to estimate the log fold-change of the genes involved and to identify those that are differentially expressed within the same model framework. We investigate the operating characteristics of our method using simulation and spike-in studies, and illustrate its application to real data using a breast-cancer dataset.

Journal Article↗
PubMed2000

Identification by RNA fingerprinting of genes differentially expressed during the development of the basidiomycete Lentinula edodes.

As part of an ongoing project to understand the molecular mechanisms of fruit body development in Lentinula edodes (Shiitake mushroom), RNA fingerprinting by arbitrarily primed PCR (RAP-PCR) was used to identify differentially expressed genes in RNA populations from four stages of L. edodes development vegetative mycelium, primordium, young fruit body and mature fruit body. From 30 RNA fingerprints, we cloned and sequenced 33 RAP fragments after their differential expression patterns had been verified by reverse Northern dot-blot hybridization. Thirteen RAP fragments show high sequence similarity to known gene products which are involved in (1) transport across the plasma membrane (drug efflux pump and sugar transporter); (2) cell cycle control (cyclin B); (3) signal transduction and transcriptional regulation (mitogen-activated protein kinase, Cdc39/Not1, PriA, Jun-D); (4) intracellular molecule trafficking (ubiquitin, plasma membrane proton ATPase, and alpha-adaptin); (5) mitochondrial biogenesis (mitochondrial processing peptidase beta-subunit, mitochondrial glycerol-3-phosphate dehydrogenase); and (6) intermediary metabolism (fructose 1,6 bisphosphatase). The transcript levels for plasma membrane proton ATPase and alpha-adaptin remained constant, whereas the other eleven genes were differentially expressed during L. edodes. development. The expression profiles of the genes suggest that transport across the plasma membrane is important in the mycelial stage. Specific signal transduction and transcriptional controls may play important roles during the initiation of primordia and the formation of young fruiting bodies. When the mushroom matures, expression of genes involved in metabolic pathways becomes prominent. The isolation of these genes indicates their involvement in homobasidiomycete development and suggests new directions for molecular studies on mechanisms of mushroom development.

Amino Acid Sequence↗
PubMed2006

Analysis of differentially expressed proteins in cancerous and normal colonic tissues.

AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer. METHODS: Colon tissues (normal and cancerous) were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer. RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified. CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.

Adenocarcinoma↗
PubMed2001

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

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.

Acute Disease↗