Component plane presentation integrated self‐organizing map for microarray data analysis

Li, Xiao; Wang, Kankan; Teng, Yue; Ji, Zhang

doi:10.1016/s0014-5793(03)00156-x

Cited by 58 publications

(61 citation statements)

References 14 publications

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“…Hybridization for each sample was repeated at least twice, and only data with a high correlation coefficient (Ն0.95) were further analyzed. For data mining, we used SOM, which exerts distinct advantages in both gene clustering and its visualization (8). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia

Zheng

Wang

Zhang

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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239

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Understanding the complexity and dynamics of cancer cells in response to effective therapy requires hypothesis-driven, quantitative, and high-throughput measurement of genes and proteins at both spatial and temporal levels. This study was designed to gain insights into molecular networks underlying the clinical synergy between retinoic acid (RA) and arsenic trioxide (ATO) in acute promyelocytic leukemia (APL), which results in a high-quality disease-free survival in most patients after consolidation with conventional chemotherapy. We have applied an approach integrating cDNA microarray, 2D gel electrophoresis with MS, and methods of computational biology to study the effects on APL cell line NB4 treated with RA, ATO, and the combination of the two agents and collected in a time series. Numerous features were revealed that indicated the coordinated regulation of molecular networks from various aspects of granulocytic differentiation and apoptosis at the transcriptome and proteome levels. These features include an array of transcription factors and cofactors, activation of calcium signaling, stimulation of the IFN pathway, activation of the proteasome system, degradation of the PML-RAR␣ oncoprotein, restoration of the nuclear body, cell-cycle arrest, and gain of apoptotic potential. Hence, this investigation has provided not only a detailed understanding of the combined therapeutic effects of RA͞ATO in APL but also a road map to approach hematopoietic malignancies at the systems level.systems biology ͉ self-organizing map A cute promyelocytic leukemia (APL) is a form of acute myeloid leukemia that responds remarkably to the effect of differentiation-induction by all-trans-retinoic acid and the differentiation͞ apoptosis-inducing effect of arsenic trioxide (ATO). Cytogenetically, a translocation t(15;17)(q22;q21) is found in most APL patients, resulting in the formation of the promyelocytic leukemiaretinoic acid receptor ␣ (PML-RAR␣) fusion gene (1). The chimeric protein encoded by the fusion gene oligomerizes with retinoid-X receptor (RXR) and disrupts the retinoic acid (RA) signal pathway, which is essential for granulocytic differentiation. PML-RAR␣ can also form a homodimer that competes with RAR␣ for binding to the RA-response elements of target genes and binds to the corepressor (CoR) complex with a much higher affinity than does the wild-type RAR␣͞RXR. This change leads to transcriptional repression under physiological concentrations of RA and, thus, blocks cell differentiation. Pharmacological concentrations of RA can convert the PML-RAR␣ fusion protein from a transcription repressor to a transcription activator, resulting in the release of the CoR and the recruitment of a coactivator (CoA) complex. The RA treatment can also trigger degradation of the PML-RAR␣ protein via the ubiquitin͞proteasome (U͞P) pathway and, thus, trigger reassembly of the nuclear body (NB) (2). On the other hand, ATO induces partial differentiation and͞or apoptosis of APL cells in a dose-dependent manner. Importantly, cellular and m...

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Section: Resultsmentioning

confidence: 99%

Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia

Zheng

Wang

Zhang

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

239

188

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“…The normalized intensity values of treated and control cultures were used to generate ratio and log 2 expression values for each gene. Self-organizing map (SOM) analysis (Xiao et al, 2003) Quantitative real-time PCR verification. Quantitative RT-PCR was performed on selected genes to verify the differential gene expression observed through microarray data analysis.…”

Section: Methodsmentioning

confidence: 99%

“…SOM analysis (Garrigues et al, 2005;Wang et al, 2002;Xiao et al, 2003) was performed on the complete dataset of 3182 transcriptionally active genes to construct a transcriptional map. SOM analysis organized the 3182 genes into 62 groups (0-61), with the number of genes in each group ranging from 23 to 337.…”

Section: Construction Of a Transcriptional Mapmentioning

confidence: 99%

Identification of cell cycle regulators in Mycobacterium tuberculosis by inhibition of septum formation and global transcriptional analysis

2006

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In Mycobacterium tuberculosis the mechanism of septum formation and regulation of cell division remains undefined. In other bacterial species FtsZ polymerization and septum formation are influenced through protein interactions in addition to transcriptional regulation, and the combination of these provides tight regulation of this process. However, homologues of proteins known to affect FtsZ assembly have not been identified and substantiated in M. tuberculosis. This suggests that M. tuberculosis may possess unique processes for regulation of septum formation. To begin to address this poorly understood aspect of M. tuberculosis physiology, FtsZ inhibitors were used to block cell division and the effects on bacterial morphology and the transcriptional response were examined. Inhibition of septum formation prevented cell division and led to bacterial filamentation. Microarray-based transcriptional profiling allowed the evaluation of multiple metabolic processes in response to inhibition of septum formation and when coupled with bioinformatics provided a means to identify regulatory elements and other gene products that probably influence septum formation. INTRODUCTIONCell division at the molecular level has been well studied in a number of bacteria and it is recognized that septum formation is the first committed step of this event (Harry et al., 1999). In general, inhibition of bacterial division at the point of septum formation is characterized by normal chromosome replication and segregation that is not followed by cellular division leading to a filamentous phenotype . Septum formation is dependent on the assembly of FtsZ into the contractile Z-ring at the site of division (Den Blaauwen et al., 1999;Romberg & Levin, 2003) and additional proteins recruited to the septum site in a sequential fashion, resulting in constriction and cell division. In spite of this biochemical information, the current understanding of regulatory elements and the precise nature of the signals driving the coordination of cell division with other cell cycle processes is largely unknown, especially in Mycobacterium tuberculosis.Many of the proteins involved in cell division, such as FtsZ, are conserved across taxa, while others appear limited to one or a few bacterial groups Margolin, 2000). These include proteins known to interact with FtsZ and that modulate Z-ring assembly Romberg & Levin, 2003). The Z-ring is highly dynamic, and proper assembly of this structure and cell division are strongly influenced by direct interactions of FtsZ with ZipA, ZapA, FtsA, MinD, EzrA and SulA (Harry et al., 1999;Harry, 2001;Migocki et al., 2004;Romberg & Levin, 2003). These factors together with transcriptional regulators form a regulatory network that orchestrates the spatial and temporal control of cell division with other cell cycle processes. However, the underlying molecular mechanisms are only partially understood in model organisms and remain largely unknown for many unrelated organisms.Analysis of the M. tuberculosis genome sequence revealed t...

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“…Illustration of the SOM outputs by component plane presentations (CPPs) was conducted in the Matlab 6.5 environment as described previously. 17,18 SOM outputs and functionally important genes were tabulated (Tables S1 and S2, available on the Blood website; see on the Supplemental Tables link at the top of the online article).…”

Section: Microarray and Data Miningmentioning

confidence: 99%

“…17,18 As shown in Figure 2A, each presentation illustrates a treatment-or sample-specific, global transcriptional map, allowing us not only to directly correlate the functional significance of genes in each unit with respect to the sample or treatment condition, but also to compare global changes within and between the different treatment series. For instance, presentations of the imatinib mesylate (S) series share some similar regulatory patterns with those of the ATO (A) series, implicating the presence of some commonly/similarly regulated genes in these 2 treatment series.…”

Section: Data Mining and Visualization By Cpp-sommentioning

confidence: 99%

Coordination of intrinsic, extrinsic, and endoplasmic reticulum-mediated apoptosis by imatinib mesylate combined with arsenic trioxide in chronic myeloid leukemia

Wang

Fang

et al. 2006

Blood

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A treatment strategy that combines arsenic trioxide (ATO) with the tyrosine kinase inhibitor imatinib mesylate (STI571, Gleevec) appears to induce markedly more cell apoptosis than imatinib mesylate alone in chronic myeloid leukemia (CML). To understand the mechanisms underlying the synergistic/additive action of these agents, we applied cDNA microarrays, component plane presentation integrated self-organizing map (CPP-SOM), and methods of protein biochemistry to study cell apoptosis induced by imatinib mesylate, ATO, and the combination of the 2 agents in the CML cell line K562. Numerous features with temporospatial relationships were revealed, indicating the coordinated regulation of molecular networks from various aspects of proapoptotic and apoptotic activities in CML. Imatinib mesylate appears to induce mainly the intrinsic pathway of cell apoptosis, whereas ATO induces the endoplasmic reticulum (ER) stress-mediated pathway of cell apoptosis, and the combination of the 2 agents seems to more effectively induce the intrinsic, extrinsic, and ER stress-mediated pathways of cell apoptosis, which results in a more effective and efficient induction of programmed cell death in K562 cells. This finding appears to be supported also by data de- IntroductionAdvances in molecular pathogenesis have facilitated the development of therapeutic strategies targeted to molecular events critical for human malignancies. This is represented by the treatment of chronic myeloid leukemia (CML) with imatinib mesylate (STI571), a specifically designed inhibitor that targets the tyrosine kinase activity of the BCR-ABL protein and consequently induces apoptosis in vitro as well as in vivo in CML cells. [1][2][3][4][5][6] Recent clinical trials in the chronic phase of CML have also demonstrated the remarkable efficacy of this molecularly targeted agent to patients with CML. 7 However, a significant proportion of the treated patients with previously failed experiences of interferon therapy remained predominantly BCR-ABL ϩ , suggesting a risk of later relapse. 8 Furthermore, patients in the accelerated and blast-crisis phase revealed a high frequency of relapse or resistance to imatinib mesylate. 9-11 As a result, much interest is now focused on the development of combination therapies to improve response rates and prevent resistance or relapse. 12 Arsenic, the oldest and also the newest form of antileukemia drug, may promote apoptosis and exert anti-CML effects. 13 A treatment strategy that combines arsenic compounds that lower BCR-ABL levels, with imatinib mesylate that inhibits BCR-ABL tyrosine kinase activity, has indeed shown promising potential in inducing more apoptosis in BCR-ABL ϩ cells. [14][15][16] Clinical applications of similar strategies may potentially strengthen the curative effects of imatinib mesylate. To better evaluate additive or synergistic effects of the combination of ATO with imatinib mesylate in CML cells, and to develop more sophisticated clinical protocols, we treated the CML cell line K562 with ATO, imatinib...

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Component plane presentation integrated self‐organizing map for microarray data analysis

Cited by 58 publications

References 14 publications

Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia

Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia

Identification of cell cycle regulators in Mycobacterium tuberculosis by inhibition of septum formation and global transcriptional analysis

Coordination of intrinsic, extrinsic, and endoplasmic reticulum-mediated apoptosis by imatinib mesylate combined with arsenic trioxide in chronic myeloid leukemia

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