Abstract：
BACKGROUND:Breast cancer remains the most lethal type of cancer for women. A significant proportion of breast cancer cases are characterised by overexpression of the human epidermal growth factor receptor 2 protein (HER2). These cancers are commonly treated by Herceptin (Trastuzumab), but resistance to drug treatment frequently develops in tumour cells. Dual-specificity phosphatases (DUSPs) are thought to play a role in the mechanism of resistance, since some of them were reported to be overexpressed in tumours resistant to Herceptin. RESULTS:We used a systems biology approach to investigate how DUSP overexpression could favour cell proliferation and to predict how this mechanism could be reversed by targeted inhibition of selected DUSPs. We measured the expression of 20 DUSP genes in two breast cancer cell lines following long-term (6 months) exposure to Herceptin, after confirming that these cells had become resistant to the drug. We constructed several Boolean models including specific substrates of each DUSP, and showed that our models correctly account for resistance when overexpressed DUSPs were kept activated. We then simulated inhibition of both individual and combinations of DUSPs, and determined conditions under which the resistance could be reversed. CONCLUSIONS:These results show how a combination of experimental analysis and modelling help to understand cell survival mechanisms in breast cancer tumours, and crucially enable us to generate testable predictions potentially leading to new treatments of resistant tumours.
journal_name
Comput Biol Chemjournal_title
Computational biology and chemistryauthors
Buiga P,Elson A,Tabernero L,Schwartz JMdoi
10.1016/j.compbiolchem.2019.03.018subject
Has Abstractpub_date
2019-06-01 00:00:00pages
138-146eissn
1476-9271issn
1476-928Xpii
S1476-9271(19)30191-4journal_volume
80pub_type
杂志文章abstract：:Interleukin-1β is a drug target in rheumatoid arthritis and several auto-immune disorders. In this study, a set of 48 compounds with the determined IC50 values were used for QSAR analysis by MOE. The QSAR model was developed by using training set of 41 compounds, based on 12 unique descriptors. Model was validated by ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2015.06.004
更新日期：2015-10-01 00:00:00
abstract：:Microarray technology has been widely applied in study of measuring gene expression levels for thousands of genes simultaneously. Gene cluster analysis is found useful for discovering the function of gene because co-expressed genes are likely to share the same biological function. K-means is one of well-known clusteri...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2008.03.020
更新日期：2008-08-01 00:00:00
abstract：:Archaea represent an important and vast domain of life. This cellular domain includes a large diversity of organisms characterized as prokaryotes with basal transcriptional machinery similar to eukarya. In this work we explore the most recent findings concerning the transcriptional regulatory organization in archaeal ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.compbiolchem.2011.10.006
更新日期：2011-12-14 00:00:00
abstract：:Glucokinase (GK) is the main enzyme which controls the blood glucose levels in a safe and narrow physiological range in humans. GK activators are the novel type of therapeutic agents which act on GK enzyme and show their anti-diabetic potential. The present work was planned to synthesize and evaluate the antidiabetic ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2018.02.018
更新日期：2018-04-01 00:00:00
abstract：:Accurately and reliably identifying the actual number of clusters present with a dataset of gene expression profiles, when no additional information on cluster structure is available, is a problem addressed by few algorithms. GeneMCL transforms microarray analysis data into a graph consisting of nodes connected by edg...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2005.07.002
更新日期：2005-10-01 00:00:00
abstract：:The present study is focused on a series of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimide derivatives, as potential anticonvulsants. The retention behavior of eleven succinimide derivatives was determined by using reversed phase high performance liquid chromatography (RP-HPLC) and reversed phase high performanc...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2019.107161
更新日期：2020-02-01 00:00:00
abstract：:Identifying essential proteins is very important for understanding the minimal requirements of cellular survival and development. Fast growth in the amount of available protein-protein interactions has produced unprecedented opportunities for detecting protein essentiality from the network level. Essential proteins ha...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2011.04.002
更新日期：2011-06-01 00:00:00
abstract：:The accurate prognostic prediction is essential for precise diagnosis and treatment of carcinoma. In addition to clinical survival prediction method, many computational methods based on transcriptomic data have been proposed to build the prediction models and study the prognosis of cancer patients. We propose a differ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107317
更新日期：2020-10-01 00:00:00
abstract：:Previous joint experimental and theoretical work demonstrates that typically soluble peptides will be rendered insoluble in the presence of saturated sodium ions in aqueous solution due to disruption of cation-π interactions between Trp and Lys. The present work utilizes quantum chemical methods including density func...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2017.12.009
更新日期：2018-02-01 00:00:00
abstract：:MicroRNAs (miRNAs) have been implicated in complex vertebrate developmental and pathological systems as a versatile class of molecules involved in the regulation of various biological processes and molecular pathways. To elucidate the role of miRNAs in human somatic cells, an understanding of the molecular framework r...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2009.09.003
更新日期：2009-12-01 00:00:00
abstract：:The presence of repetitive or non-unique DNA persisting over sizable regions of a eukaryotic genome can hinder the genome's successful de novo assembly from short reads: ambiguities in assigning genome locations to the non-unique subsequences can result in premature termination of contigs and thus overfragmented assem...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2016.02.016
更新日期：2016-04-01 00:00:00
abstract：:Many Traditional Chinese Medicines (TCMs) are effective to relieve complicated diseases such as type II diabetes mellitus (T2DM). In this work, molecular docking and network analysis were employed to elucidate the action mechanism of a medical composition which had clinical efficacy for T2DM. We found that multiple ac...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2011.07.003
更新日期：2011-10-12 00:00:00
abstract：:MODULEWRITER is a PERL object relational mapping (ORM) tool that automatically generates database specific application programming interfaces (APIs) for SQL databases. The APIs consist of a package of modules providing access to each table row and column. Methods for retrieving, updating and saving entries are provide...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/s1476-9271(03)00021-5
更新日期：2003-05-01 00:00:00
abstract：:Currently Alzheimer's disease (AD) is a devastating neurological disorder that mainly affects the elderly. The treatment of AD has as main objective to increase the levels of ACh in the synaptic cleft by inhibiting the cholinesterase enzymes, which are responsible for the degradation of ACh. Twenty one synthesized cou...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107293
更新日期：2020-05-29 00:00:00
abstract：:Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pandemic is ongoing, with no proven safe and effective vaccine to date. Further, effective therapeutic agents for COVID-19 are limited, and as a result, the identification of potential small molecule antiviral drugs is of particul...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107408
更新日期：2020-12-01 00:00:00
abstract：BACKGROUND:Metastasis is the main cause of breast cancer (BC) lethality, especially in early stages, led to improvements in therapeutic procedures. Lately, by improvements in our perception of biological processes and immune system new classes of vaccines are emerged that grant us the opportunity of designing resolute ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107231
更新日期：2020-04-01 00:00:00
abstract：:Development in two-dimensional (2D) drug-delivery materials have quickly translated into biological and pharmacological fields. In this present work, pristine graphene (PG) and hexagonal boron nitride (h-BN) sheets are explored as a drug carrier for cytarabine (CYT) and clofarabine (CLF) anti-cancer drugs using densit...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107334
更新日期：2020-10-01 00:00:00
abstract：:MicroRNAs are important negative regulators of gene expression in higher eukaryotes. The miRNA repertoire of the closest human animal relative, the chimpanzee (Pan troglodytes), is largely unknown. In this study, we focused on computational search of novel miRNA homologs in chimpanzee. We have searched and analyzed th...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2008.07.024
更新日期：2009-02-01 00:00:00
abstract：BACKGROUND:The current availability of public protein-protein interaction (PPI) databases which are usually modelled as PPI networks has led to the rapid development of protein function prediction approaches. The existing network-based prediction approaches mainly focus on the topological similarities between immediate...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2013.01.002
更新日期：2013-06-01 00:00:00
abstract：:Reptin functions in a wide range of biological processes including chromatin remodelling, nucleolar organization and transcriptional regulation of WNT signalling. As β-catenin dependent transcriptional repression and activation events involve binding of Reptin and histone deacetylase 1 to APPL endocytic proteins, this...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2013.05.005
更新日期：2013-12-01 00:00:00
abstract：:The DNA binding protein, TDP43 is a major protein involved in amyotrophic lateral sclerosis and other neurological disorders such as frontotemporal dementia, Alzheimer disease, etc. In the present study, we have designed possible siRNAs for the glycine rich region of tardbp mutants causing ALS disorder based on a syst...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2016.01.001
更新日期：2016-04-01 00:00:00
abstract：:Protein function prediction is a crucial task in the post-genomics era due to their diverse irreplaceable roles in a biological system. Traditional methods involved cost-intensive and time-consuming molecular biology techniques but they proved to be ineffective after the outburst of sequencing data through the advent ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2019.107147
更新日期：2019-12-01 00:00:00
abstract：:Structural class characterizes the overall folding type of a protein or its domain. Many methods have been proposed to improve the prediction accuracy of protein structural class in recent years, but it is still a challenge for the low-similarity sequences. In this study, we introduce a feature extraction technique ba...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2015.08.012
更新日期：2015-12-01 00:00:00
abstract：:Accurate clustering of cells from single-cell RNA sequencing (scRNA-seq) data is an essential step for biological analysis such as putative cell type identification. However, scRNA-seq data has high dimension and high sparsity, which makes traditional clustering methods less effective to reflect the similarity between...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107415
更新日期：2020-11-18 00:00:00
abstract：:Cell type identification from an unknown sample can often be done by comparing its gene expression profile against a gene expression database containing profiles of a large number of cell-types. This type of compendium-based cell-type identification strategy is particularly successful for human and mouse samples becau...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2018.10.003
更新日期：2018-12-01 00:00:00
abstract：:Protein-ligand docking is an essential process that has accelerated drug discovery. How to accurately and effectively optimize the predominant position and orientation of ligands in the binding pocket of a target protein is a major challenge. This paper proposed a novel ligand binding pose search method called FWAVina...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107363
更新日期：2020-10-01 00:00:00
abstract：:A computational study of the interaction of cardiac troponin I (cTnI) with its specific antibody and of that antibody with skeletal troponin I (sTnI), the principal interferon of cTnI, is carried out. Computational and simulation tools such as FTSite, FTMap, FTDock and pyDock are used to determine the binding sites of...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2019.04.002
更新日期：2019-06-01 00:00:00
abstract：:The QSAR models for a set of pyrazolo[4,3-e][1,2,4]triazines incorporating benzenesulfonamide moiety combined directly with the heterocyclic ring or by NH linkage were generated. The inhibitory potency of compounds against human carbonic anhydrase isoforms IX and XII and antiproliferative activity against human MCF-7 ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2017.09.006
更新日期：2017-12-01 00:00:00
abstract：:Nanoscopic properties of TiO2 augmented with its physicochemical properties and biocompatibility make it a material interest in the biomedical field. Efficient methods to design of such materials require a thorough understanding of associated nano-bio interfaces. In the present study, density functional theory calcula...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107236
更新日期：2020-06-01 00:00:00
abstract：:Up to this date, there has been an ongoing debate about the mode of action of general anesthetics, which have postulated many biological sites as targets for their action. However, postoperative nausea and vomiting are common problems in which inhalational agents may have a role in their development. When a mode of ac...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2018.04.009
更新日期：2018-08-01 00:00:00
