scholarly journals Bayesian combination of mechanistic modeling and machine learning (BaM3): improving clinical tumor growth predictions

2020 ◽  
Author(s):  
Pietro Mascheroni ◽  
Symeon Savvopoulos ◽  
Juan Carlos López Alfonso ◽  
Michael Meyer-Hermann ◽  
Haralampos Hatzikirou

AbstractBiomedical problems are highly complex and multidimensional. Commonly, only a small subset of the relevant variables can be modeled by virtue of mathematical modeling due to lack of knowledge of the involved phenomena. Although these models are effective in analyzing the approximate dynamics of the system, their predictive accuracy is generally limited. On the other hand, statistical learning methods are well-suited for quantitative reproduction of data, but they do not provide mechanistic understanding of the investigated problem. Herein, we propose a novel method, based on the Bayesian coupling of mathematical modeling and machine learning (BaM3). We evaluate the proposed BaM3 method on a synthetic dataset for brain tumor growth as a proof of concept and analyze its performance in predicting two major clinical outputs, namely tumor burden and infiltration. Combining these two approaches results in improved predictions in almost all simulated patients, especially for those with a late clinical presentation. In addition, we test the proposed methodology on a set of patients suffering from Chronic Lymphocytic Leukemia (CLL) and show excellent agreement with reported data.

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Pietro Mascheroni ◽  
Symeon Savvopoulos ◽  
Juan Carlos López Alfonso ◽  
Michael Meyer-Hermann ◽  
Haralampos Hatzikirou

Abstract Background In clinical practice, a plethora of medical examinations are conducted to assess the state of a patient’s pathology producing a variety of clinical data. However, investigation of these data faces two major challenges. Firstly, we lack the knowledge of the mechanisms involved in regulating these data variables, and secondly, data collection is sparse in time since it relies on patient’s clinical presentation. The former limits the predictive accuracy of clinical outcomes for any mechanistic model. The latter restrains any machine learning algorithm to accurately infer the corresponding disease dynamics. Methods Here, we propose a novel method, based on the Bayesian coupling of mathematical modeling and machine learning, aiming at improving individualized predictions by addressing the aforementioned challenges. Results We evaluate the proposed method on a synthetic dataset for brain tumor growth and analyze its performance in predicting two relevant clinical outputs. The method results in improved predictions in almost all simulated patients, especially for those with a late clinical presentation (>95% patients show improvements compared to standard mathematical modeling). In addition, we test the methodology in two additional settings dealing with real patient cohorts. In both cases, namely cancer growth in chronic lymphocytic leukemia and ovarian cancer, predictions show excellent agreement with reported clinical outcomes (around 60% reduction of mean squared error). Conclusions We show that the combination of machine learning and mathematical modeling approaches can lead to accurate predictions of clinical outputs in the context of data sparsity and limited knowledge of disease mechanisms.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13508-e13508
Author(s):  
Sylvie Retout ◽  
Alex Phipps ◽  
David Geho ◽  
Jean Tessier ◽  
Gwen L. Nichols ◽  
...  

e13508 Background: Tumor size change from baseline (RECIST) is often used to assess antitumor activity of investigational agents in phase 1 trials, but this measure does not take into account the tumor growth rate (TGR) prior to treatment. TGR could be highly variable in a phase 1 ‘all-comers’ patient population, with a high TGR potentially masking a meaningful treatment effect (TE). Assessing the change in TGR (Mehrara et al, BJC 2011) using historical tumor burden assessments (Gomez-Roca et al, Eur J Cancer 2011) may provide higher sensitivity to true TE (TTE). The objectives of the current study are to formalize a Growth Rate Based Method (GRBM) and to compare, using simulated patients, the ability of GRBM and RECIST assessments to detect and quantify TTE. Methods: The exponential tumor growth model (Claret et al, J Clin Oncol. 2009) was used to simulate the sum of the longest diameters (SLD) individual time courses of 2000 virtual patients under different TGR scenarios: slow, medium, fast and ‘all comers’ (highly variable TGR as often encountered in phase 1). Different sampling designs were simulated wherein tumor assessments with measurement errors were obtained, ranging from 16 to 4 weeks prior to treatment initiation (TI), immediately before TI, and 8 and 16 weeks after TI. TTE was defined as the difference between the simulated SLDs at 16 weeks with and without treatment. GRBM response was defined as the model-predicted difference between the SLDs with and without treatment, as estimated from the simulated samples. Sensitivity (Se) of RECIST or GRBM was defined as the probability of classifying a patient as a RECIST or GRBM >30% reduction when the TTE >30%, and specificity (Sp) as the probability of RECIST or GRBM reduction <30% when TTE <30%. Results: RECIST Se was consistently inferior to GRBM, notably in the all-comers TGR (37% vs 74-89%) scenario. GRBM maintained Se (71-89%) irrespective of TGR whereas RECIST Se degraded significantly with increasing TGR. RECIST Sp was high (97-100%) while GRBM Sp was lower (55-80%) depending on sampling design and TGR. Conclusions: Incorporation of an additional pretreatment tumor assessment by GRBM may augment RECIST by increasing sensitivity to TTE, particularly in a heterogeneous TGR phase 1 setting.


2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 97-97
Author(s):  
Andrea Phillips Sitlinger ◽  
Peter A. Ubel ◽  
Tian Zhang ◽  
Charlene Wong ◽  
Rishi Sachdev ◽  
...  

97 Background: Insurance plans vary coverage for infusional (IV) vs oral drugs, leading some to suggest that patients on oral drugs pay more OOP than those on IV drugs. 43 states have passed laws requiring insurers to cover oral drugs equivalently to IV drugs. Yet, there is little evidence that these “parity laws” are effective. Our aim was to estimate impact of parity laws on OOP expenses for oral vs IV drugs. Methods: We sought to determine how quickly patients on oral vs IV drugs reach their plan’s annual OOP maximum (max) as a surrogate for OOP expense. We used 2017 data from Healthcare.gov public use files to generate cost-sharing profiles for all 3,092 unique Marketplace plans. Chronic lymphocytic leukemia (CLL) and metastatic hormone sensitive prostate cancer (mHSPC) were chosen as two representative malignancies since both have accepted, first-line, IV and oral treatment options. We created guideline-concordant, first-line treatment regimens for simulated patients with CLL (oral ibrutinib vs IV bendamustine/rituximab) or mHSPC (oral abiraterone vs IV docetaxel). Drug, professional, facility, imaging, and lab claims were simulated to calculate OOP costs. The mean number of days to reach the OOP maximum for each Marketplace plan and treatment regimen were recorded. We assessed variation according to insurance coverage levels (“metal tier”: Catastrophic, Bronze, Silver, Gold, Platinum). Results: For CLL patients, 95% of plans reached OOP max in approximately one month of treatment for both oral and IV drugs (oral: mean 36 days; IV: mean 29 days). 99% of mHSPC patients reached their OOP max for oral treatment in a mean 15 days, but only 57% of plans reached OOP max for IV mHSPC treatment. Metal tier impacts time to reach OOP max (table). Conclusions: Parity laws do not lower patient costs when both IV and oral treatment options are expensive. In these cases, patients reach the OOP max rapidly. The small subset of patients most likely to benefit from parity laws are those on oral therapy for a disease where the comparable IV drug is inexpensive (eg, generic docetaxel for mHSPC). [Table: see text]


2019 ◽  
Author(s):  
Ryther Anderson ◽  
Achay Biong ◽  
Diego Gómez-Gualdrón

<div>Tailoring the structure and chemistry of metal-organic frameworks (MOFs) enables the manipulation of their adsorption properties to suit specific energy and environmental applications. As there are millions of possible MOFs (with tens of thousands already synthesized), molecular simulation, such as grand canonical Monte Carlo (GCMC), has frequently been used to rapidly evaluate the adsorption performance of a large set of MOFs. This allows subsequent experiments to focus only on a small subset of the most promising MOFs. In many instances, however, even molecular simulation becomes prohibitively time consuming, underscoring the need for alternative screening methods, such as machine learning, to precede molecular simulation efforts. In this study, as a proof of concept, we trained a neural network as the first example of a machine learning model capable of predicting full adsorption isotherms of different molecules not included in the training of the model. To achieve this, we trained our neural network only on alchemical species, represented only by their geometry and force field parameters, and used this neural network to predict the loadings of real adsorbates. We focused on predicting room temperature adsorption of small (one- and two-atom) molecules relevant to chemical separations. Namely, argon, krypton, xenon, methane, ethane, and nitrogen. However, we also observed surprisingly promising predictions for more complex molecules, whose properties are outside the range spanned by the alchemical adsorbates. Prediction accuracies suitable for large-scale screening were achieved using simple MOF (e.g. geometric properties and chemical moieties), and adsorbate (e.g. forcefield parameters and geometry) descriptors. Our results illustrate a new philosophy of training that opens the path towards development of machine learning models that can predict the adsorption loading of any new adsorbate at any new operating conditions in any new MOF.</div>


2020 ◽  
Author(s):  
Uzair Bhatti

BACKGROUND In the era of health informatics, exponential growth of information generated by health information systems and healthcare organizations demands expert and intelligent recommendation systems. It has become one of the most valuable tools as it reduces problems such as information overload while selecting and suggesting doctors, hospitals, medicine, diagnosis etc according to patients’ interests. OBJECTIVE Recommendation uses Hybrid Filtering as one of the most popular approaches, but the major limitations of this approach are selectivity and data integrity issues.Mostly existing recommendation systems & risk prediction algorithms focus on a single domain, on the other end cross-domain hybrid filtering is able to alleviate the degree of selectivity and data integrity problems to a better extent. METHODS We propose a novel algorithm for recommendation & predictive model using KNN algorithm with machine learning algorithms and artificial intelligence (AI). We find the factors that directly impact on diseases and propose an approach for predicting the correct diagnosis of different diseases. We have constructed a series of models with good reliability for predicting different surgery complications and identified several novel clinical associations. We proposed a novel algorithm pr-KNN to use KNN for prediction and recommendation of diseases RESULTS Beside that we compared the performance of our algorithm with other machine algorithms and found better performance of our algorithm, with predictive accuracy improving by +3.61%. CONCLUSIONS The potential to directly integrate these predictive tools into EHRs may enable personalized medicine and decision-making at the point of care for patient counseling and as a teaching tool. CLINICALTRIAL dataset for the trials of patient attached


2020 ◽  
Author(s):  
Hsiao-Ko Chang ◽  
Hui-Chih Wang ◽  
Chih-Fen Huang ◽  
Feipei Lai

BACKGROUND In most of Taiwan’s medical institutions, congestion is a serious problem for emergency departments. Due to a lack of beds, patients spend more time in emergency retention zones, which make it difficult to detect cardiac arrest (CA). OBJECTIVE We seek to develop a Drug Early Warning System Model (DEWSM), it included drug injections and vital signs as this research important features. We use it to predict cardiac arrest in emergency departments via drug classification and medical expert suggestion. METHODS We propose this new model for detecting cardiac arrest via drug classification and by using a sliding window; we apply learning-based algorithms to time-series data for a DEWSM. By treating drug features as a dynamic time-series factor for cardiopulmonary resuscitation (CPR) patients, we increase sensitivity, reduce false alarm rates and mortality, and increase the model’s accuracy. To evaluate the proposed model, we use the area under the receiver operating characteristic curve (AUROC). RESULTS Four important findings are as follows: (1) We identify the most important drug predictors: bits (intravenous therapy), and replenishers and regulators of water and electrolytes (fluid and electrolyte supplement). The best AUROC of bits is 85%, it means the medical expert suggest the drug features: bits, it will affect the vital signs, and then the evaluate this model correctly classified patients with CPR reach 85%; that of replenishers and regulators of water and electrolytes is 86%. These two features are the most influential of the drug features in the task. (2) We verify feature selection, in which accounting for drugs improve the accuracy: In Task 1, the best AUROC of vital signs is 77%, and that of all features is 86%. In Task 2, the best AUROC of all features is 85%, which demonstrates that thus accounting for the drugs significantly affects prediction. (3) We use a better model: For traditional machine learning, this study adds a new AI technology: the long short-term memory (LSTM) model with the best time-series accuracy, comparable to the traditional random forest (RF) model; the two AUROC measures are 85%. It can be seen that the use of new AI technology will achieve better results, currently comparable to the accuracy of traditional common RF, and the LSTM model can be adjusted in the future to obtain better results. (4) We determine whether the event can be predicted beforehand: The best classifier is still an RF model, in which the observational starting time is 4 hours before the CPR event. Although the accuracy is impaired, the predictive accuracy still reaches 70%. Therefore, we believe that CPR events can be predicted four hours before the event. CONCLUSIONS This paper uses a sliding window to account for dynamic time-series data consisting of the patient’s vital signs and drug injections. The National Early Warning Score (NEWS) only focuses on the score of vital signs, and does not include factors related to drug injections. In this study, the experimental results of adding the drug injections are better than only vital signs. In a comparison with NEWS, we improve predictive accuracy via feature selection, which includes drugs as features. In addition, we use traditional machine learning methods and deep learning (using LSTM method as the main processing time series data) as the basis for comparison of this research. The proposed DEWSM, which offers 4-hour predictions, is better than the NEWS in the literature. This also confirms that the doctor’s heuristic rules are consistent with the results found by machine learning algorithms.


2021 ◽  
Vol 40 (5) ◽  
pp. 9471-9484
Author(s):  
Yilun Jin ◽  
Yanan Liu ◽  
Wenyu Zhang ◽  
Shuai Zhang ◽  
Yu Lou

With the advancement of machine learning, credit scoring can be performed better. As one of the widely recognized machine learning methods, ensemble learning has demonstrated significant improvements in the predictive accuracy over individual machine learning models for credit scoring. This study proposes a novel multi-stage ensemble model with multiple K-means-based selective undersampling for credit scoring. First, a new multiple K-means-based undersampling method is proposed to deal with the imbalanced data. Then, a new selective sampling mechanism is proposed to select the better-performing base classifiers adaptively. Finally, a new feature-enhanced stacking method is proposed to construct an effective ensemble model by composing the shortlisted base classifiers. In the experiments, four datasets with four evaluation indicators are used to evaluate the performance of the proposed model, and the experimental results prove the superiority of the proposed model over other benchmark models.


Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 763
Author(s):  
Ran Yang ◽  
Zhenbo Wang ◽  
Jiajia Chen

Mechanistic-modeling has been a useful tool to help food scientists in understanding complicated microwave-food interactions, but it cannot be directly used by the food developers for food design due to its resource-intensive characteristic. This study developed and validated an integrated approach that coupled mechanistic-modeling and machine-learning to achieve efficient food product design (thickness optimization) with better heating uniformity. The mechanistic-modeling that incorporated electromagnetics and heat transfer was previously developed and validated extensively and was used directly in this study. A Bayesian optimization machine-learning algorithm was developed and integrated with the mechanistic-modeling. The integrated approach was validated by comparing the optimization performance with a parametric sweep approach, which is solely based on mechanistic-modeling. The results showed that the integrated approach had the capability and robustness to optimize the thickness of different-shape products using different initial training datasets with higher efficiency (45.9% to 62.1% improvement) than the parametric sweep approach. Three rectangular-shape trays with one optimized thickness (1.56 cm) and two non-optimized thicknesses (1.20 and 2.00 cm) were 3-D printed and used in microwave heating experiments, which confirmed the feasibility of the integrated approach in thickness optimization. The integrated approach can be further developed and extended as a platform to efficiently design complicated microwavable foods with multiple-parameter optimization.


1993 ◽  
Vol 18 (2-4) ◽  
pp. 209-220
Author(s):  
Michael Hadjimichael ◽  
Anita Wasilewska

We present here an application of Rough Set formalism to Machine Learning. The resulting Inductive Learning algorithm is described, and its application to a set of real data is examined. The data consists of a survey of voter preferences taken during the 1988 presidential election in the U.S.A. Results include an analysis of the predictive accuracy of the generated rules, and an analysis of the semantic content of the rules.


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