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Lee C.K., Klopp R.G., Weindruch R., Prolla T.A. Gene expression profile of aging and its retardation by caloric restriction. Science. 285:1999;1390-1393. This paper brings the study of changes in gene transcription as a function of age under the scope of microarray technology. Transcripts derived from the calf muscles of young and old mice were compared, using Affymetrix chips. Additionally, caloric-restricted old mice were compared to free-fed old mice. The authors found changes in genes related to stress response, energy metabolism, protein turnover, and neuronal factors. Caloric restriction, which is known to extend life span in some organisms, reversed many of the aging-related changes, but was associated overall with other unique responses affecting genes involved in synthesis of fatty acids, glutamine, steroids and nucleotides.
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The authors examined immediate early gene induction mediated by the cytoplasmic domain of the PDGF receptor, a receptor tyrosine kinase. After constructing a series of distinct cytoplasmic Tyr→Phe mutations, they used Affymetrix chips specifying 6000 mouse genes and ESTs to evaluate the dependence of immediate early genes on distinct signaling pathways. Surprisingly, they found that individual signaling pathways make a quantitative rather than a qualitative contribution to the transcriptional response to ligand. A mutant receptor defective for signaling via at least three pathways still induced 64 of the normal 66 genes in response to ligand, but the average level of induction was 59% of wild type.
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Fambrough D., McClure K., Kazlauskas A., Lander E.S. Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes. Cell. 97:1999;727-741. The authors examined immediate early gene induction mediated by the cytoplasmic domain of the PDGF receptor, a receptor tyrosine kinase. After constructing a series of distinct cytoplasmic Tyr→Phe mutations, they used Affymetrix chips specifying 6000 mouse genes and ESTs to evaluate the dependence of immediate early genes on distinct signaling pathways. Surprisingly, they found that individual signaling pathways make a quantitative rather than a qualitative contribution to the transcriptional response to ligand. A mutant receptor defective for signaling via at least three pathways still induced 64 of the normal 66 genes in response to ligand, but the average level of induction was 59% of wild type.
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Working with Affymetrix chips for the detection of yeast transcripts, the authors examined the dependence of yeast transcription on components of the general transcription machinery. Evaluations were based on comparisons between wild-type yeast and deletion mutants (in the case of non-essential components) or conditional mutations (in the case of essential components). Different perturbations had differing impacts on global transcription, ranging from nearly absolute inhibition (in strains depleted for RNA polymerase II large subunit) to 3% inhibition (in strains deleted for SRB10, a regulatory protein kinase).
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Hilsenbeck, S.G.1
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Wittes J., Friedman H.P. Searching for evidence of altered gene expression: a comment on statistical analysis of microarray data. J Natl Cancer Inst. 91:1999;400-401.
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Wittes, J.1
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Systematic determination of genetic network architecture
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Tavazoie S., Hughes J.D., Campbell M.J., Cho R.J., Church G.M. Systematic determination of genetic network architecture. Nat Genet. 22:1999;281-285.
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Church, G.M.5
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44
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0033027794
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Interpreting patterns of gene expression with self-organizing maps: Methods and application to hematopoietic differentiation
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This paper describes the method for clustering genes based on their expression profiles using self-organizing maps (SOMs). The associated software can be applied to either intensity data or ratiometric data, and displays the mean behavior of the genes in a cluster, rather than displaying the patterns of variation of the individual genes forming a cluster.
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Tamayo P., Slonim D., Mesirov J., Zhu Q., Kitareewan S., Dmitrovsky E., Lander E.S., Golub T.R. Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation. Proc Natl Acad Sci USA. 96:1999;2907-2912. This paper describes the method for clustering genes based on their expression profiles using self-organizing maps (SOMs). The associated software can be applied to either intensity data or ratiometric data, and displays the mean behavior of the genes in a cluster, rather than displaying the patterns of variation of the individual genes forming a cluster.
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Proc Natl Acad Sci USA
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Tamayo, P.1
Slonim, D.2
Mesirov, J.3
Zhu, Q.4
Kitareewan, S.5
Dmitrovsky, E.6
Lander, E.S.7
Golub, T.R.8
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45
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0033536012
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Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays
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Alon U., Barkai N., Notterman D.A., Gish K., Ybarra S., Mack D., Levine A.J. Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc Natl Acad Sci USA. 96:1999;6745-6750.
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Proc Natl Acad Sci USA
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Alon, U.1
Barkai, N.2
Notterman, D.A.3
Gish, K.4
Ybarra, S.5
Mack, D.6
Levine, A.J.7
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46
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Analysis of gene expression data using self-organizing maps
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Toronen P., Kolehmainen M., Wong G., Castren E. Analysis of gene expression data using self-organizing maps. FEBS Lett. 451:1999;142-146.
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FEBS Lett
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Toronen, P.1
Kolehmainen, M.2
Wong, G.3
Castren, E.4
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47
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0033597939
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Genetic selection of peptide inhibitors of biological pathways
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Twenty peptides were identified that allowed yeast cells to proliferate in the presence of mating pheromone. By genetic criteria, the peptides were hypothesized to function by reversing silencing of a silenced mating-type locus, converting the haploid yeast into functional a/α diploids, which are pheromone insensitive. To test their hypothesis, the authors used a microarray to compare the effect of the peptides with the effect of a known mutation that destroys silencing. They found a significant degree of correlation, confirming the specificity of the action of the peptides.
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Norman T.C., Smith D.L., Sorger P.K., Drees B.L., O'Rourke S.M., Hughes T.R., Roberts C.J., Friend S.H., Fields S., Murray A.W. Genetic selection of peptide inhibitors of biological pathways. Science. 285:1999;591-595. Twenty peptides were identified that allowed yeast cells to proliferate in the presence of mating pheromone. By genetic criteria, the peptides were hypothesized to function by reversing silencing of a silenced mating-type locus, converting the haploid yeast into functional a/α diploids, which are pheromone insensitive. To test their hypothesis, the authors used a microarray to compare the effect of the peptides with the effect of a known mutation that destroys silencing. They found a significant degree of correlation, confirming the specificity of the action of the peptides.
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(1999)
Science
, vol.285
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Norman, T.C.1
Smith, D.L.2
Sorger, P.K.3
Drees, B.L.4
O'Rourke, S.M.5
Hughes, T.R.6
Roberts, C.J.7
Friend, S.H.8
Fields, S.9
Murray, A.W.10
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48
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0031730097
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Drug target validation and identification of secondary drug target effects using DNA microarrays
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This paper offers a creative application of transcription profiling to the challenge of identifying useful drugs. Typically, drugs have partially known effects and poorly known targets. The authors use transcript profiles to determine 'signatures' for the effects of both drugs and mutations. When a drug and a mutation have similar signatures, it suggests the drug targets the gene involved in the mutation, but confirmation is necessary. A second tier experiment is done, wherein the mutant strain itself is exposed to the drug, to evaluate residual response. Finding uncorrelated drug responses between wild-type and mutant strains suggests that the drug specifically targets the gene affected by the mutation.
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Marton M.J., DeRisi J.L., Bennett H.A., Iyer V.R., Meyer M.R., Roberts C.J., Stoughton R., Burchard J., Slade D., Dai H.et al. Drug target validation and identification of secondary drug target effects using DNA microarrays. Nat Med. 4:1998;1293-1301. This paper offers a creative application of transcription profiling to the challenge of identifying useful drugs. Typically, drugs have partially known effects and poorly known targets. The authors use transcript profiles to determine 'signatures' for the effects of both drugs and mutations. When a drug and a mutation have similar signatures, it suggests the drug targets the gene involved in the mutation, but confirmation is necessary. A second tier experiment is done, wherein the mutant strain itself is exposed to the drug, to evaluate residual response. Finding uncorrelated drug responses between wild-type and mutant strains suggests that the drug specifically targets the gene affected by the mutation.
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(1998)
Nat Med
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Marton, M.J.1
Derisi, J.L.2
Bennett, H.A.3
Iyer, V.R.4
Meyer, M.R.5
Roberts, C.J.6
Stoughton, R.7
Burchard, J.8
Slade, D.9
Dai, H.10
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49
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0033538465
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Ploidy regulation of gene expression
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The authors derived 11 closely related yeast strains whose ploidies spanned the range from haploid to tetraploid. Working with Affymetrix chips, they determined expression intensities for all genes. For each gene in each strain (1N, 2N, 3N and 4N), they correlated expression intensities to the reference series 1, 2, 3, 4 and 1, 0.5, 0.33, 0.25. They found 17 genes showing significant correlation to the reference series. One gene showing repression at higher ploidies (CLN1) was already known to have a disruption phenotype of increased cell volume. The inverse relation between ploidy and expression for CLN1 may contribute to the larger cell volume of higher ploidy cells.
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Galitski T., Saldanha A.J., Styles C.A., Lander E.S., Fink G.R. Ploidy regulation of gene expression. Science. 285:1999;251-254. The authors derived 11 closely related yeast strains whose ploidies spanned the range from haploid to tetraploid. Working with Affymetrix chips, they determined expression intensities for all genes. For each gene in each strain (1N, 2N, 3N and 4N), they correlated expression intensities to the reference series 1, 2, 3, 4 and 1, 0.5, 0.33, 0.25. They found 17 genes showing significant correlation to the reference series. One gene showing repression at higher ploidies (CLN1) was already known to have a disruption phenotype of increased cell volume. The inverse relation between ploidy and expression for CLN1 may contribute to the larger cell volume of higher ploidy cells.
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(1999)
Science
, vol.285
, pp. 251-254
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Galitski, T.1
Saldanha, A.J.2
Styles, C.A.3
Lander, E.S.4
Fink, G.R.5
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50
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0032846163
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Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array
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These authors describe a novel approach to the in situ synthesis of oligonucleotide arrays using light-directed chemistry, but without the use of photolithographic masks. Rather, they use a computer-controlled array of micro-mirrors to focus light on specific regions of the reaction chamber during oligonucleotide synthesis. A similar approach was taken by HR Garner (HR Garner, personal communication).
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Singh-Gasson S., Green R.D., Yue Y., Nelson C., Blattner F., Sussman M.R., Cerrina F. Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array. Nat Biotechnol. 17:1999;974-978. These authors describe a novel approach to the in situ synthesis of oligonucleotide arrays using light-directed chemistry, but without the use of photolithographic masks. Rather, they use a computer-controlled array of micro-mirrors to focus light on specific regions of the reaction chamber during oligonucleotide synthesis. A similar approach was taken by HR Garner (HR Garner, personal communication).
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(1999)
Nat Biotechnol
, vol.17
, pp. 974-978
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Singh-Gasson, S.1
Green, R.D.2
Yue, Y.3
Nelson, C.4
Blattner, F.5
Sussman, M.R.6
Cerrina, F.7
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