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Results for “model selection”

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PubMedDate not supplied

Variable selection and model validation of 2D and 3D molecular descriptors.

We have found that molecular shape and electrostatics, in conjunction with 2D structural fingerprints, are important variables in discriminating classes of active and inactive compounds. The subject of this paper is how to explore the selection of these variables and identify their relative importance in quantitative structure-activity relationships (QSAR) analysis. We show the use of these variables in a form of similarity searching with respect to a crystal structure of a known bound ligand. This analysis is then validated through k-fold cross-validation of enrichments via several common classifiers. Additionally, we show an effective methodology using the variables in hypothesis generation; namely, when the crystal structure of a bound ligand is not known.

Calcium Channels↗
PubMed2001

An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3.

Although interleukin (IL)-12 and IL-4 polarize naive CD4(+) T cells toward T helper cell type 1 (Th1) or Th2 phenotypes, it is not known whether cytokines instruct the developmental fate in uncommitted progenitors or select for outgrowth of cells that have stochastically committed to a particular fate. To distinguish these instructive and selective models, we used surface affinity matrix technology to isolate committed progenitors based on cytokine secretion phenotype and developed retroviral-based tagging approaches to directly monitor individual progenitor fate decisions at the clonal and population levels. We observe IL-4-dependent redirection of phenotype in cells that have already committed to a non-IL-4-producing fate, inconsistent with predictions of the selective model. Further, retroviral tagging of naive progenitors with the Th2-specific transcription factor GATA-3 provided direct evidence for instructive differentiation, and no evidence for the selective outgrowth of cells committed to either the Th1 or Th2 fate. These data would seem to exclude selection as an exclusive mechanism in Th1/Th2 differentiation, and support an instructive model of cytokine-driven transcriptional programming of cell fate decisions.

Animals↗
PubMed2004

Performance of a genetic algorithm for mass spectrometry proteomics.

BACKGROUND: Recently, mass spectrometry data have been mined using a genetic algorithm to produce discriminatory models that distinguish healthy individuals from those with cancer. This algorithm is the basis for claims of 100% sensitivity and specificity in two related publicly available datasets. To date, no detailed attempts have been made to explore the properties of this genetic algorithm within proteomic applications. Here the algorithm's performance on these datasets is evaluated relative to other methods. RESULTS: In reproducing the method, some modifications of the algorithm as it is described are necessary to get good performance. After modification, a cross-validation approach to model selection is used. The overall classification accuracy is comparable though not superior to other approaches considered. Also, some aspects of the process rely upon random sampling and thus for a fixed dataset the algorithm can produce many different models. This raises questions about how to choose among competing models. How this choice is made is important for interpreting sensitivity and specificity results as merely choosing the model with lowest test set error rate leads to overestimates of model performance. CONCLUSIONS: The algorithm needs to be modified to reduce variability and care must be taken in how to choose among competing models. Results derived from this algorithm must be accompanied by a full description of model selection procedures to give confidence that the reported accuracy is not overstated.

Algorithms↗
PubMed2004

Modifying the Schwarz Bayesian information criterion to locate multiple interacting quantitative trait loci.

The problem of locating multiple interacting quantitative trait loci (QTL) can be addressed as a multiple regression problem, with marker genotypes being the regressor variables. An important and difficult part in fitting such a regression model is the estimation of the QTL number and respective interactions. Among the many model selection criteria that can be used to estimate the number of regressor variables, none are used to estimate the number of interactions. Our simulations demonstrate that epistatic terms appearing in a model without the related main effects cause the standard model selection criteria to have a strong tendency to overestimate the number of interactions, and so the QTL number. With this as our motivation we investigate the behavior of the Schwarz Bayesian information criterion (BIC) by explaining the phenomenon of the overestimation and proposing a novel modification of BIC that allows the detection of main effects and pairwise interactions in a backcross population. Results of an extensive simulation study demonstrate that our modified version of BIC performs very well in practice. Our methodology can be extended to general populations and higher-order interactions.

Bayes Theorem↗
PubMed2003

Chiral 3,3'-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] with anti-inflammatory activity. Part 11: evaluation of COX-2 selectivity and modelling.

Anti-inflammatory/analgesic 3,3'-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] 1, obtained as racemic mixtures (a) and mesoforms (b), have two equivalent stereogenic centres (C-2 and C-2') and exist as RR, SS and RS isomers. The enantioseparation of 1a provided the single enantiomers that displayed different in vitro cyclooxygenase-1/cyclooxygenase-2 selectivity ratios. In particular the dextrorotatory compound is a highly selective COX-2 inhibitor and the levorotatory one is moderately selective. Instead, RS-meso isomer (1b) exhibited similar levels of inhibitory activity on both COX isozymes. The diastereo- and enantioselectivity has been explained by molecular modelling of RR, SS and RS compounds into COX-1 and COX-2 binding sites. Theoretical results indicated SS>RS>RR affinity order towards COX-2 isoenzyme, in agreement with in vitro and previous in vivo pharmacological results.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Dissecting affinity maturation: a model explaining selection of antibody-forming cells and memory B cells in the germinal centre.

Until recently, the relationship between apoptosis, selection in the germinal centre (GC) and production of high-affinity antibody-forming cells (AFCs) and memory B cells has been unclear. Here, Tarlinton and Smith present a model that accounts for the switch in GC production from high-affinity AFCs to memory B cells, and explain how Bcl-2, an inhibitor of apoptosis, can influence memory cells but not bone marrow AFCs.

Animals↗
PubMedDate not supplied

Development of feedforward receptive field structure of a simple cell and its contribution to the orientation selectivity: a modeling study.

Recent experimental studies of hetero-synaptic interactions in various systems have shown the role of signaling in the plasticity, challenging the conventional understanding of Hebb's rule. It has also been found that activity plays a major role in plasticity, with neurotrophins acting as molecular signals translating activity into structural changes. Furthermore, role of synaptic efficacy in biasing the outcome of competition has also been revealed recently. Motivated by these experimental findings we present a model for the development of simple cell receptive field structure based on the competitive hetero-synaptic interactions for neurotrophins combined with cooperative hetero-synaptic interactions in the spatial domain. We find that with proper balance in competition and cooperation, the inputs from two populations (ON/OFF) of LGN cells segregate starting from the homogeneous state. We obtain segregated ON and OFF regions in simple cell receptive field. Our modeling study supports the experimental findings, suggesting the role of synaptic efficacy and the role of spatial signaling. We find that using this model we obtain simple cell RF, even for positively correlated activity of ON/OFF cells. We also compare different mechanism of finding the response of cortical cell and study their possible role in the sharpening of orientation selectivity. We find that degree of selectivity improvement in individual cells varies from case to case depending upon the structure of RF field and type of sharpening mechanism.

Animals↗
PubMed1987

Quantitative genetic models of sexual selection: a review.

Quantitative genetic models of sexual selection have disproven some of the central tenets of both the handicap mechanism and the 'sexy son' hypothesis. These results suggest that the 'good genes' approach to sexual selection may often lead to erroneous results. Runaway sexual selection seems possible under a wide variety of circumstances. Quantitative genetic models have revealed runaway processes for sexually selected attributes expressed in both sexes and for attributes of parental care. Furthermore, the runaway could occur simultaneously in a series of populations that straddle an environmental gradient. While the models support the feasibility of runaway processes, empirical studies are needed to evaluate whether runaways actually happen. Estimates of critical genetic parameters are particularly needed, as well as measures of natural and sexual selection acting on the same population. The models also show that sexual selection has tremendous potential to produce population differentiation, particularly in epigamic traits. Differentiation is promoted by indeterminancy of evolutionary outcome, transient differences among populations during the final slow approach to equilibrium, sampling drift among equilibrium populations, and the tendency of sexual selection to amplify geographic variation arising from spatial differences in natural selection. Recent work with two- and three-locus models of sexual selection has produced results that parallel the results of the polygenic models (Kirkpatrick, 1982, 1985, 1986; Seger, 1985). Thus the feature of indeterminate equilibria (outcome dependent on initial conditions) is common to both types of model.

Animals↗
PubMed2002

An independently derived and validated predictive model for selecting patients with myocardial infarction who are likely to benefit from tissue plasminogen activator compared with streptokinase.

BACKGROUND: In the Global Utilization of Streptokinase and tPA for Occluded coronary arteries (GUSTO) trial, patients with myocardial infarction who were treated with tissue plasminogen activator (tPA) had a 6.3% 30-day mortality, compared with a mortality of 7.3% among those treated with streptokinase, despite a greater risk of intracranial hemorrhage with tPA. However, in part because of its higher cost, tPA has not been adopted universally. METHODS: Using an independently developed model, we predicted the benefits of tPA therapy in the 24,146 patients in the GUSTO trial and compared these predictions with the actual benefits of tPA, after classifying patients by their risks of mortality and intracranial hemorrhage. We also performed a "patient-specific" cost-effectiveness analysis among different strata of expected benefit of tPA. RESULTS: Our model predicted that among patients with myocardial infarction, 61% of the benefit of tPA use in reducing mortality accrued to only 25% of patients; treating half of patients could capture 85% of the benefit. Including the risk of intracranial hemorrhage, our model predicted that treating half the GUSTO patients with tPA and the others with streptokinase would yield similar outcomes as treating all patients with tPA, because the additional risk of intracranial hemorrhage exceeded the expected benefit in some patients. When patients were stratified into quartiles of risk, the observed outcomes in the GUSTO patients corresponded well with these predicted results. The estimated cost-effectiveness of tPA was sensitive to patient characteristics. CONCLUSION: For selected patients, use of tPA yields substantially better outcomes than streptokinase, and use of the less expensive agent is difficult to justify. For many patients, however, tPA is unlikely to provide any additional benefit and, in some patients, it may even cause net harm.

Adult↗
PubMed2005

Construct validity of the animal latent inhibition model of selective attention deficits in schizophrenia.

Latent inhibition (LI) is demonstrated when a previously unattended/inconsequential stimulus is less effective in a new learning situation than a novel stimulus. In rats and humans, LI is reduced by dopamine agonists and increased by dopamine antagonists. In addition, LI is attenuated in actively psychotic schizophrenia patients, thus conferring strong predictive validity to the animal LI preparation for schizophrenia. However, the validity of the attentional construct in the LI model of schizophrenia dysfunction depends on confirming two assumptions: that animal and human LI share a common process, and that the process is related to selective attention. Evidence to support both assumptions is presented, followed by a description of a conditioned attention theory that emphasizes the role of initial levels of attention elicited by repeated relevant and irrelevant stimuli, and the differences between these levels in schizophrenia and normal groups.

Animals↗
PubMed2026

Is a Win-Win possible? Achieving pareto-optimal privacy-utility balance in fine-tuned genome language model embeddings against embedding reconstruction attacks.

MOTIVATION: Genomic data is among the most sensitive categories of personal information, and the growing adoption of language models for sequence analysis raises significant privacy concerns. Prior work demonstrated that embeddings from general-purpose language models adapted for genomic sequences leak substantial single-nucleotide information under reconstruction attacks, and that fine-tuning embeddings can reduce this vulnerability at certain positions. However, three critical questions remain unaddressed: (i) whether privacy-utility tradeoffs are inherent constraints or configuration-dependent phenomena; (ii) whether genomic-specialized models such as DNABERT-base and Nucleotide Transformer exhibit different vulnerabilities than adapted general-purpose models; and (iii) how to statistically validate whether observed privacy improvements represent meaningful gains. Addressing these gaps is essential for guiding model selection in privacy-sensitive genomic applications. RESULTS: We systematically evaluated 13 transformer architectures, 9 general-purpose and 4 genomic-specialized, under position-specific embedding reconstruction attacks. We assessed the vulnerabilities of both pre-trained and fine-tuned models to the single-nucleotide inference-reconstruction attack using our new metrics, including error-based privacy gain and Pareto dominance scores, and statistically validated the results via paired t-tests. XLNet-Large achieved the best observed privacy protection among all evaluated models (+19.5% mean privacy gain) while maintaining competitive prediction performance. General-purpose models outperformed genomic-specialized models in 56% of pairwise comparisons. Tokenization strategy, rather than domain specialization, emerged as the primary determinant of the privacy-utility balance. These findings provide evidence-based guidance for selecting models in privacy-sensitive short-window genomic applications. All privacy claims in this work are specific to position-wise embedding reconstruction attacks and do not extend to other privacy risks, such as membership inference or training data extraction, which may respond differently to fine-tuning. AVAILABILITY AND IMPLEMENTATION: The code is publicly available at https://github.com/AnonymousISCBConf/Win-Win-Privacy-Utility-Analysis.

Genomics↗
PubMed2002

Outcomes and sample selection: the case of a homelessness and substance abuse intervention.

In the likely event that some clients refuse to participate in a psychosocial field experiment, the estimates of the effects of the experimental treatment on client outcomes may suffer from sample selection bias, regardless of whether the statistical analyses include control variables. This paper explores ways of correcting for this bias with advanced correction strategies, focusing on experiments in which clients refuse assignment into treatment conditions. The sample selection modelling strategy, which is highly recommended but seldom applied to random sample psychosocial experiments, and some alternatives are discussed. Data from an experiment on homelessness and substance abuse are used to compare sample selection, conventional control variable, instrumental variable, and propensity score matching correction strategies. The empirical findings suggest that the sample selection modelling strategy provides reliable estimates of the effects of treatment, that it and some other correction strategies are awkward to apply when there is post-assignment rejection, and that the varying correction strategies provide widely divergent estimates. In light of these findings, researchers might wish regularly to compare estimates across multiple correction strategies.

Adult↗
PubMed2006

A theoretical study to investigate D2DAR/D4DAR selectivity: receptor modeling and molecular docking of dopaminergic ligands.

Molecular modeling methods have been applied to construct three-dimensional models for dopaminergic ligand complexes with D2 and D4 receptor subtypes (D2DAR and D4DAR), using the bovine rhodopsin crystal structure as a template for the modeling study. Different dopaminergic ligands, in particular the N-n-propyl-substituted 3-aryl- and 3-cyclohexylpiperidines, were docked into the D2DAR and the D4DAR, to evaluate the agreement between theoretical and experimental results as regards their D2/D4 selectivity. The different position of an aromatic region in the two receptors might explain the structural basis of this biological property.

Amino Acid Sequence↗
PubMed1996

Role of animal models in selecting antiviral combinations for clinical studies.

Although experimental viral infections in animals have been used extensively in the development of antiviral drugs used as monotherapy, they have not been utilized widely for evaluation of combination chemotherapy. One of the major reasons for the lack of use of animal models is that for the diseases that are the main target for combination therapy, AIDS and hepatitis B and C infections, there is a lack of suitable models for these diseases. In contrast, most combination studies in animal models have been directed against herpes simplex virus infections but there are relatively few patients available who would benefit from combination therapy over single agent therapy. In between those two extremes are the cytomegalovirus infections. While there are animal models available that have been predictive of efficacy in humans and there are sufficient patients available, the use of antiviral combinations in animal models and in humans have begun only recently. At the present time there is not enough information available to establish the predictability for any of the animal models for efficacy of combinations of antiviral agents.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Modeling embryogenesis and cancer: an approach based on an equilibrium between the autostabilization of stochastic gene expression and the interdependence of cells for proliferation.

A large amount of data demonstrating the stochastic nature of gene expression and cell differentiation has accumulated during the last 40 years. These data suggest that a gene in a cell always has a certain probability of being activated at any time and that instead of leading to on and off switches in an all-or-nothing fashion, the concentration of transcriptional regulators increases or decreases this probability. In order to integrate these data in an appropriate theoretical frame, we have tested the relevance of the selective model of cell differentiation by computer simulation experiments. This model is based on stochastic gene expression controlled by cellular interactions. Our results show that it is readily able to produce tissue organization. A model involving only two cells generated a bi-layer cellular structure of finite growth. Cell death was not a drawback but an advantage because it improved the viability of this bi-layer structure. However, our results also show that cellular interactions cannot be simply based on raw selection between cells. Instead, tissue coordination includes at least two basic components: phenotypic autostabilization (differentiated cells stabilize their own phenotype) and interdependence for proliferation (differentiated cells stimulate the proliferation of alien phenotypes). In this modified autostabilization-selection model, cellular organization and growth arrest result from a quantitative equilibrium between the parameters controlling these two processes. An imbalance leads to tissue disorganization and invasive cancer-like growth. These findings suggest that cancer does not result solely from mutations in the cancerous cell but from the progressive addition of several small alterations of the equilibrium between autostabilization and interdependence for proliferation. In this frame, it is not solely the cancerous cell that is abnormal. The whole organism is involved. Tumor growth is a local effect of an imbalance between all the factors involved in tissue organization.

Animals↗
PubMed1993

Model for selecting quality standards for a salad bar through identifying elements of customer satisfaction.

Continuous quality improvement is the new requirement of the Joint Commission on Accreditation of Healthcare Organizations. This means that meeting quality standards will not be enough. Dietitians will need to improve those standards and the way they are selected. Because quality is defined in terms of the customers, all quality improvement projects must start by defining what customers want. Using a salad bar as an example, this article presents and illustrates a technique developed in Japan to identify which elements in a product or service will satisfy or dissatisfy consumers. Using a model and a questionnaire format developed by Kano and coworkers, 273 students were surveyed to classify six quality elements of a salad bar. Four elements showed a dominant "must-be" characteristic: food freshness, labeling of the dressings, no spills in the food, and no spills on the salad bar. The two other elements (food easy to reach and food variety) showed a dominant one-dimensional characteristic. By better understanding consumer perceptions of quality elements, foodservice managers can select quality standards that focus on what really matters to their consumers.

Consumer Behavior↗