Rule-based modelling
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- MeSH
- algoritmy MeSH
- anestezie škodlivé účinky MeSH
- asfyxie diagnóza etiologie komplikace MeSH
- fraktály MeSH
- hypoxie plodu diagnóza etiologie komplikace MeSH
- komplikace těhotenství diagnóza etiologie MeSH
- lidé MeSH
- počítačová simulace trendy využití MeSH
- srdeční frekvence plodu fyziologie MeSH
- srdeční zástava diagnóza etiologie komplikace MeSH
- teoretické modely MeSH
- výchova a vzdělávání MeSH
- Check Tag
- lidé MeSH
A major challenge in cancer treatment is predicting the clinical response to anti-cancer drugs on a personalized basis. The success of such a task largely depends on the ability to develop computational resources that integrate big "omic" data into effective drug-response models. Machine learning is both an expanding and an evolving computational field that holds promise to cover such needs. Here we provide a focused overview of: 1) the various supervised and unsupervised algorithms used specifically in drug response prediction applications, 2) the strategies employed to develop these algorithms into applicable models, 3) data resources that are fed into these frameworks and 4) pitfalls and challenges to maximize model performance. In this context we also describe a novel in silico screening process, based on Association Rule Mining, for identifying genes as candidate drivers of drug response and compare it with relevant data mining frameworks, for which we generated a web application freely available at: https://compbio.nyumc.org/drugs/. This pipeline explores with high efficiency large sample-spaces, while is able to detect low frequency events and evaluate statistical significance even in the multidimensional space, presenting the results in the form of easily interpretable rules. We conclude with future prospects and challenges of applying machine learning based drug response prediction in precision medicine.
BACKGROUND: Our purpose is to assess epidemiological agent-based models-or ABMs-of the SARS-CoV-2 pandemic methodologically. The rapid spread of the outbreak requires fast-paced decision-making regarding mitigation measures. However, the evidence for the efficacy of non-pharmaceutical interventions such as imposed social distancing and school or workplace closures is scarce: few observational studies use quasi-experimental research designs, and conducting randomized controlled trials seems infeasible. Additionally, evidence from the previous coronavirus outbreaks of SARS and MERS lacks external validity, given the significant differences in contagiousness of those pathogens relative to SARS-CoV-2. To address the pressing policy questions that have emerged as a result of COVID-19, epidemiologists have produced numerous models that range from simple compartmental models to highly advanced agent-based models. These models have been criticized for involving simplifications and lacking empirical support for their assumptions. METHODS: To address these voices and methodologically appraise epidemiological ABMs, we consider AceMod (the model of the COVID-19 epidemic in Australia) as a case study of the modelling practice. RESULTS: Our example shows that, although epidemiological ABMs involve simplifications of various sorts, the key characteristics of social interactions and the spread of SARS-CoV-2 are represented sufficiently accurately. This is the case because these modellers treat empirical results as inputs for constructing modelling assumptions and rules that the agents follow; and they use calibration to assert the adequacy to benchmark variables. CONCLUSIONS: Given this, we claim that the best epidemiological ABMs are models of actual mechanisms and deliver both mechanistic and difference-making evidence. Consequently, they may also adequately describe the effects of possible interventions. Finally, we discuss the limitations of ABMs and put forward policy recommendations.
Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.
- MeSH
- Bayesova věta MeSH
- elektrická stimulace metody MeSH
- epilepsie * MeSH
- evokované potenciály * fyziologie MeSH
- lidé MeSH
- mapování mozku metody MeSH
- mozek MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This statement paper provides a brief and clear background to the evidence-based medicine concept, systematic reviews and the development of clinical practice guidelines using the Grading of Recommendations, Assessment, Development and Eva luation (GRADE) system and focuses on their application in the fi eld of special education.Its main objective is to suggest ways of applying clinical practice guidelines in the fi eld of special education. Th e paper presents the fi rst Czech national project for developing clinical practice guidelines mainly in the fi eld of medicine and clinical practice with the main investigator being the Czech Health Research Council (AZV ČR). Some of the guidelines prepared within the project are relevant to special educators and the paper suggests that special teachers use the recommendations in their practice and in higher education. Moreover, it proposes that it is possible and useful to develop guidelines using the rigor of the GRADE methodology as described above, for issues directly pertaining to the fi eld of special education, or education in general. In that process, it may be neces-sary to identify the challenges typical for the fi eld of education and to suggest possible solutions. Finally, recommendations for special educators, for future research and for policy-makers are formulated. Specifi cally, the paper suggests that policy-makers, such as the Ministry of Education, Youth and Sports, develop national strategies for spe -cial-edu cational diagnostics and intervention based on rigorous methodology as des cribed on the example of the Czech national project of guideline development in medi cine and place special focus on the ethical aspects, social impacts and values and preferences of target populations.
- Klíčová slova
- vzdělávací politika,
- MeSH
- integrovaná výuka MeSH
- interdisciplinární výzkum organizace a řízení MeSH
- lidé MeSH
- medicína založená na důkazech normy MeSH
- metody pro podporu rozhodování MeSH
- postižení výchova MeSH
- pravidla klinického rozhodování MeSH
- programy národního zdraví organizace a řízení MeSH
- speciální vzdělávání * etika normy MeSH
- vytváření politiky MeSH
- vzdělávací modely MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
This research proposes an assessment and decision support model to use when a driver should be examined about their propensity for traffic accidents, based on an estimation of the driver's psychological traits. The proposed model was tested on a sample of 305 drivers. Each participant completed four psychological tests: the Barratt Impulsiveness Scale (BIS-11), the Aggressive Driving Behaviour Questionnaire (ADBQ), the Manchester Driver Attitude Questionnaire (DAQ) and the Questionnaire for Self-assessment of Driving Ability. In addition, participants completed an extensive demographic and driving survey. Various fuzzy inference systems were tested and each was defined using the well-known Wang-Mendel method for rule-base definition based on empirical data. For this purpose, a programming code was designed and utilized. Based on the obtained results, it was determined which combination of the considered psychological tests provides the best prediction of a driver's propensity for traffic accidents. The best of the considered fuzzy inference systems might be used as a decision support tool in various situations, such as in recruitment procedures for professional drivers. The validity of the proposed fuzzy approach was confirmed as its implementation provided better results than from statistics, in this case multiple regression analysis.
- MeSH
- agrese MeSH
- bezpečnost MeSH
- dopravní nehody * MeSH
- dospělí MeSH
- fuzzy logika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- postoj MeSH
- průzkumy a dotazníky MeSH
- psychologické modely * MeSH
- regresní analýza MeSH
- řízení motorových vozidel psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Computational systems biology provides multiple formalisms for modelling of biochemical processes among which the rule-based approach is one of the most suitable. Its main advantage is a compact and precise mechanistic description of complex processes. However, state-of-the-art rule-based languages still suffer several shortcomings that limit their use in practice. In particular, the elementary (low-level) syntax and semantics of rule-based languages complicate model construction and maintenance for users outside computer science. On the other hand, mathematical models based on differential equations (ODEs) still make the most typical used modelling framework. In consequence, robust re-interpretation and integration of models are difficult, thus making the systems biology paradigm technically challenging. Though several high-level languages have been developed at the top of rule-based principles, none of them provides a satisfactory and complete solution for semi-automated description and annotation of heterogeneous biophysical processes integrated at the cellular level. We present the second generation of a rule-based language called Biochemical Space Language (BCSL) that combines the advantages of different approaches and thus makes an effort to overcome several problems of existing solutions. BCSL relies on the formal basis of the rule-based methodology while preserving user-friendly syntax of plain chemical equations. BCSL combines the following aspects: the level of abstraction that hides structural and quantitative details but yet gives a precise mechanistic view of systems dynamics; executable semantics allowing formal analysis and consistency checking at the level of the language; universality allowing the integration of different biochemical mechanisms; scalability and compactness of the specification; hierarchical specification and composability of chemical entities; and support for genome-scale annotation.
- MeSH
- algoritmy MeSH
- biochemické jevy * MeSH
- biologické modely * MeSH
- jazyk (prostředek komunikace) MeSH
- lidé MeSH
- počítačová simulace * MeSH
- programovací jazyk MeSH
- proteiny chemie klasifikace metabolismus MeSH
- software * MeSH
- systémová biologie * MeSH
- teoretické modely MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Several constitutive models have been proposed for the description of mechanical behaviour of soft tissues containing collagen fibres. Some of the commonly used approaches accounting for the dispersion of fibre orientations are based on the summation of (mechanical) contributions of differently oriented fibre families. This leads to the need of numerical integration on the sphere surface, and the related numerical consumption is the main disadvantage of this category of constitutive models. The paper is focused on the comparison of various numerical integration methods applied to a specific constitutive model applicable for arterial walls. Robustness and efficiency of several integration rules were tested with respect to application in finite element (FE) codes. Among all the analysed numerical integration rules, the best results were reached by Lebedev quadrature; the related parameters for the specific constitutive model are presented in the paper. The results were implemented into the commercial FE code ANSYS via user subroutines, and their applicability was demonstrated by an example of FE simulation with non-homogenous stress field.
A new test of the proportional hazards assumption in the Cox model is proposed. The idea is based on Neyman's smooth tests. The Cox model with proportional hazards (i.e. time-constant covariate effects) is embedded in a model with a smoothly time-varying covariate effect that is expressed as a combination of some basis functions (e.g., Legendre polynomials, cosines). Then the smooth test is the score test for significance of these artificial covariates. Furthermore, we apply a modification of Schwarz's selection rule to choosing the dimension of the smooth model (the number of the basis functions). The score test is then used in the selected model. In a simulation study, we compare the proposed tests with standard tests based on the score process.
