Evidence map›Paper›PMID 24618474›Full record

ArticleBioinformatics (Oxford, England)2014

Characterization of p38 MAPK isoforms for drug resistance study using systems biology approach.

Huiming Peng, Tao Peng, Jianguo Wen, David A Engler, Risë K Matsunami, Jing Su, Le Zhang, Chung-Che Jeff Chang, Xiaobo Zhou

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioinformatics (Oxford, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 41 citations in OpenAlex.

  1. A Review of the Application of Spatial Transcriptomics in Neuroscience.Interdisciplinary sciences, computational life sciences · 2024
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  19. Computational systems biology in cancer brain metastasis.Frontiers in bioscience (Scholar edition) · 2016
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Huiming PengCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
Tao PengCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
Jianguo WenCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
David A EnglerCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
Risë K MatsunamiCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
Jing SuCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
Le ZhangCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
Chung-Che Jeff ChangCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
Xiaobo ZhouCenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USACenter for Bioinformatics & Systems Biology and Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA, Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Department of Pathology, The Methodist Hospital Research Institute, Houston, TX 77030, USA, Proteomics Programmatic Core Laboratory, The Methodist Hospital Research Institute, Houston, TX 77030, USA, College of Computer and Information Science, Southwest University, Chongqing 400715, China, Department of Pathology, Florida Hospital, Orlando, FL 32803, USA.
Methodist Hospital · USHouston Methodist · US

Funding

Modelling the Growth of the MIC Niche at the System LevelU01CA166886 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ZHOU, XIAOBO · 2012 to 2016
$2.2M
System Biology Approach for Signaling Transduction Study of Complex PhenotypesR01LM010185 · NLM · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ZHOU, XIAOBO, ZU, YOULI · 2009 to 2012
$1.3M
itNETZ: Integrative and Translational Network-based Cellular Signature AnalyzerU01HL111560 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ZHOU, XIAOBO · 2011 to 2013
$1.1M
NCI NIH HHS 1U01CA166886NCI NIH HHS U01 CA166886NHLBI NIH HHS 1U01HL111560NHLBI NIH HHS U01 HL111560NLM NIH HHS 1R01LM010185NLM NIH HHS R01 LM010185
6 · The paper itself

Abstract

motivationp38 mitogen-activated protein kinase activation plays an important role in resistance to chemotherapeutic cytotoxic drugs in treating multiple myeloma (MM). However, how the p38 mitogen-activated protein kinase signaling pathway is involved in drug resistance, in particular the roles that the various p38 isoforms play, remains largely unknown.

methodTo explore the underlying mechanisms, we developed a novel systems biology approach by integrating liquid chromatography-mass spectrometry and reverse phase protein array data from human MM cell lines with computational pathway models in which the unknown parameters were inferred using a proposed novel algorithm called modularized factor graph.

resultsNew mechanisms predicted by our models suggest that combined activation of various p38 isoforms may result in drug resistance in MM via regulating the related pathways including extracellular signal-regulated kinase (ERK) pathway and NFкB pathway. ERK pathway regulating cell growth is synergistically regulated by p38δ isoform, whereas nuclear factor kappa B (NFкB) pathway regulating cell apoptosis is synergistically regulated by p38α isoform. This finding that p38δ isoform promotes the phosphorylation of ERK1/2 in MM cells treated with bortezomib was validated by western blotting. Based on the predicted mechanisms, we further screened drug combinations in silico and found that a promising drug combination targeting ERK1/2 and NFκB might reduce the effects of drug resistance in MM cells. This study provides a framework of a systems biology approach to studying drug resistance and drug combination selection. AVAILABILITY AND IMPLEMENTATION: RPPA experimental Data and Matlab source codes of modularized factor graph for parameter estimation are freely available online at http://ctsb.is.wfubmc.edu/publications/modularized-factor-graph.php.

Indexed as

Drug ResistanceCell LineCell ProliferationHumansIsoenzymesNF-kappa Bp38 Mitogen-Activated Protein KinasesPhosphorylationSignal TransductionSystems BiologyIsoenzymesNF-kappa Bp38 Mitogen-Activated Protein Kinases

Identifiers

PMID24618474
PMCPMC4071201
OpenAlexW2170898372

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.