Abstract:
:A major effort in systems biology is the development of mathematical models that describe complex biological systems at multiple scales and levels of abstraction. Determining the topology-the set of interactions-of a biological system from observations of the system's behavior is an important and difficult problem. Here we present and demonstrate new methodology for efficiently computing the probability distribution over a set of topologies based on consistency with existing measurements. Key features of the new approach include derivation in a Bayesian framework, incorporation of prior probability distributions of topologies and parameters, and use of an analytically integrable linearization based on the Fisher information matrix that is responsible for large gains in efficiency. The new method was demonstrated on a collection of four biological topologies representing a kinase and phosphatase that operate in opposition to each other with either processive or distributive kinetics, giving 8-12 parameters for each topology. The linearization produced an approximate result very rapidly (CPU minutes) that was highly accurate on its own, as compared to a Monte Carlo method guaranteed to converge to the correct answer but at greater cost (CPU weeks). The Monte Carlo method developed and applied here used the linearization method as a starting point and importance sampling to approach the Bayesian answer in acceptable time. Other inexpensive methods to estimate probabilities produced poor approximations for this system, with likelihood estimation showing its well-known bias toward topologies with more parameters and the Akaike and Schwarz Information Criteria showing a strong bias toward topologies with fewer parameters. These results suggest that this linear approximation may be an effective compromise, providing an answer whose accuracy is near the true Bayesian answer, but at a cost near the common heuristics.
journal_name
Mol Biosystjournal_title
Molecular bioSystemsauthors
Hagen DR,Tidor Bdoi
10.1039/c4mb00276hsubject
Has Abstractpub_date
2015-02-01 00:00:00pages
574-84issue
2eissn
1742-206Xissn
1742-2051journal_volume
11pub_type
杂志文章abstract::Schistosomiasis is a parasitic infection that is endemic in many developing countries in the tropics and subtropics afflicting more than 207 million people primarily in rural areas. After malaria, it is the second most important parasitic infection in terms of socio-economic and public health. Investigation of the hos...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c0mb00262c
更新日期:2011-05-01 00:00:00
abstract::Cell culture metabolomics has demonstrated significant advantages in cancer research. However, its applications have been impeded by some influencing factors such as culture media, which could significantly affect cellular metabolic profiles and lead to inaccuracy and unreliability of comparative metabolomic analysis ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c5mb00019j
更新日期:2015-07-01 00:00:00
abstract::Bacterial biofilms are defined as a community of surface-attached bacteria that are protected by an extracellular matrix of biomolecules. We have recently reported the synthesis of a small molecule, denoted TAGE, based on the natural product bromoageliferin and demonstrated that TAGE has anti-biofilm activity against ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b719989a
更新日期:2008-06-01 00:00:00
abstract::A new transfection reagent based on nucleoside phosphocholine amphiphile leading to high transfection efficacy and low cytotoxicity is described. TEM, ethidium bromide displacement assays, agarose gel electrophoresis and SAXS studies support the formation of lipoplexes for the transfection of CHO cells. ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b503302k
更新日期:2005-09-01 00:00:00
abstract::In vivo analysis is of paramount importance in monitoring physiological processes that take place in living organisms. Mass spectrometry, an analytical technique with high speed, sensitivity and specificity, is indispensable in biochemical studies nowadays. However, traditional mass spectrometric techniques are of lim...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/c2mb25428j
更新日期:2013-05-01 00:00:00
abstract::Dynamic physical interactions between proteins underpin all key cellular processes and are a highly attractive area for the development of research tools and medicines. Protein-protein interactions frequently involve α-helical structures, but peptides matching the sequences of these structures usually do not fold corr...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb70246d
更新日期:2013-11-01 00:00:00
abstract::The small molecule 4-hydroxy-3-methoxybenzaldehyde (5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)hydrazone (Exo2) stimulates morphological changes at the mammalian Golgi and trans-Golgi network that are virtually indistinguishable from those induced by brefeldin A. Both brefeldin A and Exo2 protect cells from...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c0mb00035c
更新日期:2010-10-01 00:00:00
abstract::The major obstacle for the development of targeted therapies is the lack of pharmacodynamic (PD) biomarkers to provide an early readout of biological activities. As the modulation of metabolites may reflect the biological changes occurring in the targets, metabolomics is promising to be an efficient way to explore PD ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c7mb00093f
更新日期:2017-07-25 00:00:00
abstract::This paper describes a sensitive, non-destructive displacement assay, using a fluorescent peptide indicator, for real-time monitoring of the interactions between RNA and RNA binding proteins (RBPs). The developed fluorescent peptide indicators, each containing a mid-sequence fluorophore unit, allowed sensing of target...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb25470k
更新日期:2013-05-01 00:00:00
abstract::Biochemical modifications to mRNA, especially N6-methyladenosine (m6A) and 5-methylcytosine (m5C), have been recently shown to be associated with crucial biological functions. Despite the intriguing advancements, little is known so far about the dynamic landscape of RNA methylome across different cell types and how th...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c4mb00604f
更新日期:2015-01-01 00:00:00
abstract::Tankyrases (TNKS), key transmitters in the Wnt signaling pathway which is very conservative in evolution, are vital targets as they are overexpressed widely in many cancers. In this work, 5 inhibitors with novel structures have been discovered and validated using the ligand-based (pharmacophore) virtual screening, doc...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c6mb00712k
更新日期:2017-01-31 00:00:00
abstract::Remineralization of organic matter in deep-sea sediments is important in oceanic biogeochemical cycles, and bacteria play a major role in this process. Shewanella violacea DSS12 is a psychrophilic and piezophilic gamma-proteobacterium that was isolated from the surface layer of deep sea sediment at a depth of 5110 m. ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c000396d
更新日期:2010-07-01 00:00:00
abstract::Establishing functional relationships between multi-domain protein sequences is a non-trivial task. Traditionally, delineating functional assignment and relationships of proteins requires domain assignments as a prerequisite. This process is sensitive to alignment quality and domain definitions. In multi-domain protei...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb70443b
更新日期:2014-05-01 00:00:00
abstract::Blockage of the interactions between immunologic checkpoint protein PD-1 and its ligand PD-L1 showed efficacy for cancer treatment. X-ray structures have captured static conformational snapshots of PD-1 and revealed that the CC' loop adopts an open conformation in the apo-protein but turns into a closed form and inter...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c7mb00036g
更新日期:2017-05-02 00:00:00
abstract::Mannose-modified lectin-binding peptides were obtained from an α-helical-designed peptide phage library. Concanavalin A (ConA) was used as a representative target protein for the lectin family. The identified glycopeptides could selectively bind to ConA with micromolar affinity. With these results, the methodologies d...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c7mb00495h
更新日期:2017-10-24 00:00:00
abstract::In this review we bring together recent results from our group focused towards the development of biosensors from single conically-shaped artificial nanopores. The nanopores, used in the work presented here, were prepared using the track-etch process. The fabrication of track-etched conical nanopores has been optimize...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b708725j
更新日期:2007-10-01 00:00:00
abstract::Metabolomics is a rapidly growing branch of post-genomic chemical biology. The fission yeast Schizosaccharomyces pombe is an excellent eukaryotic model organism. Although the entire S. pombe genome has been sequenced and detailed transcriptomic analyses were performed, little metabolic profiling has been done. Here we...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b908784b
更新日期:2010-01-01 00:00:00
abstract::The emerging field of synthetic biology is generating insatiable demands for synthetic genes, which far exceed existing gene synthesis capabilities. This review discusses the current methods of chemical DNA synthesis and gene assembly, as well as the latest engineering tools, technologies and trends which could potent...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b822268c
更新日期:2009-07-01 00:00:00
abstract::Protein tyrosine phosphatases (PTPs) constitute a large family of enzymes that play key roles in cell signaling. Deregulation of PTP activity results in aberrant tyrosine phosphorylation, which has been linked to the etiology of several human diseases, including cancer. Since phosphate removal by the PTPs can both enh...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b700704n
更新日期:2007-05-01 00:00:00
abstract::With the advent of new cancer therapies in the last few years, the goals of reducing disease burden and improving quality of life are frequently achieved. Yet despite the advances seen with numerous monotherapies, a multimodality approach that targets different aspects of tumor biology may yield the greatest clinical ...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b911313b
更新日期:2009-11-01 00:00:00
abstract::The Parkinson's disease (PD) associated gene PINK1 encodes a protein kinase that mediates the phosphorylation of multiple proteins involved in mitochondrial homeostasis. The broader downstream signaling events mediated by PINK1 kinase activity have not been well documented. We combine quantitative phosphoproteomic str...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb70565j
更新日期:2014-07-01 00:00:00
abstract::It is not surprising that a large number of diseases related to amyloid fibril depositions are formed in various organs. Therefore, it is necessary to understand the transformation of native proteins into amyloid fibrils in order to clarify which key elements of this process determine the pathway of protein misfolding...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c5mb00273g
更新日期:2015-08-01 00:00:00
abstract::Conversion of the predominantly α-helical cellular prion protein (PrP(C)) to the misfolded β-sheet enriched Scrapie form (PrP(Sc)) is a critical event in prion pathogenesis. However, the conformational triggers that lead to the isoform conversion (PrP(C) to PrP(Sc)) remain obscure, and conjectures about the role of un...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c4mb00689e
更新日期:2015-05-01 00:00:00
abstract::High levels of DNA and RNA released by apoptotic and necrotic cells circulate in the blood of cancer patients. In the present study we determined the applicability of the quantification of nucleic acids and their genetic alterations as minimally invasive tool for breast cancer screening. The relative concentrations of...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c1mb05197k
更新日期:2011-10-01 00:00:00
abstract::In actively proliferating cells, such as the cells of the developing embryo, DNA repair is crucial for preventing the accumulation of mutations and synchronizing cell division. Sea urchin embryo growth was analyzed and extracts were prepared. The relative activity of DNA polymerase, apurinic/apyrimidinic (AP) endonucl...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c5mb00906e
更新日期:2016-06-21 00:00:00
abstract::In the last few decades a negative association between the level of milk production and fertility has been observed. Currently, the most utilized method of measuring male fertility employed by the livestock industry is related to the Non-Return Rate (NRR). Through differential proteome analysis, this study evaluated c...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb25494a
更新日期:2013-06-01 00:00:00
abstract::α-Anomers of 2'-deoxyadenosine (αdA) are major products of deoxyadenosine damage when DNA is γ-irradiated under anoxic conditions. Such lesions are a threat to genomic stability and are known to be processed by human apurinic/apyrimidinic endonuclease 1 (APE1). The aim of this study was to determine whether the α-anom...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c6mb00511j
更新日期:2016-10-18 00:00:00
abstract::The glutamate γ-carboxylation plays a pivotal part in a number of important human diseases. However, traditional protein γ-carboxylation site detection by experimental approaches are often laborious and time-consuming. In this study, we initiated an attempt for the computational prediction of protein γ-carboxylation s...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb25185j
更新日期:2012-11-01 00:00:00
abstract::Renal cell carcinoma (RCC), the most common neoplasm affecting the adult kidney, is characterised by heterogeneity of histological subtypes, drug resistance, and absence of molecular markers. Two-dimensional difference gel electrophoresis (2-D DIGE) technology in combination with mass spectrometry (MS) was applied to ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb05390j
更新日期:2012-04-01 00:00:00
abstract::Cells of the bacterium Myxococcus xanthus organize into two types of patterns depending on their nutritional status, i.e. in the presence of nutrients cells form spreading colonies and in the absence of nutrients cells form fruiting bodies. Formation of both patterns depends on directed cell movements, which, in turn,...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b806640j
更新日期:2008-10-01 00:00:00