| 1. |
- Robinson, Jonathan, 1986, et al.
(author)
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An atlas of human metabolism
- 2020
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In: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 13:624
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Journal article (peer-reviewed)abstract
- Genome-scale metabolic models (GEMs) are valuable tools to study metabolism and provide a scaffold for the integrative analysis of omics data. Researchers have developed increasingly comprehensive human GEMs, but the disconnect among different model sources and versions impedes further progress. We therefore integrated and extensively curated the most recent human metabolic models to construct a consensus GEM, Human1. We demonstrated the versatility of Human1 through the generation and analysis of cell- and tissue-specific models using transcriptomic, proteomic, and kinetic data. We also present an accompanying web portal, Metabolic Atlas (https://www.metabolicatlas.org/), which facilitates further exploration and visualization of Human1 content. Human1 was created using a version-controlled, open-source model development framework to enable community-driven curation and refinement. This framework allows Human1 to be an evolving shared resource for future studies of human health and disease.
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| 2. |
- Memedi, Mevludin, 1983-, et al.
(author)
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Automatic Spiral Analysis for Objective Assessment of Motor Symptoms in Parkinson's Disease
- 2015
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In: Sensors. - : MDPI AG. - 1424-8220. ; 15:9, s. 23727-23744
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Journal article (peer-reviewed)abstract
- A challenge for the clinical management of advanced Parkinson's disease (PD) patients is the emergence of fluctuations in motor performance, which represents a significant source of disability during activities of daily living of the patients. There is a lack of objective measurement of treatment effects for in-clinic and at-home use that can provide an overview of the treatment response. The objective of this paper was to develop a method for objective quantification of advanced PD motor symptoms related to off episodes and peak dose dyskinesia, using spiral data gathered by a touch screen telemetry device. More specifically, the aim was to objectively characterize motor symptoms (bradykinesia and dyskinesia), to help in automating the process of visual interpretation of movement anomalies in spirals as rated by movement disorder specialists. Digitized upper limb movement data of 65 advanced PD patients and 10 healthy (HE) subjects were recorded as they performed spiral drawing tasks on a touch screen device in their home environment settings. Several spatiotemporal features were extracted from the time series and used as inputs to machine learning methods. The methods were validated against ratings on animated spirals scored by four movement disorder specialists who visually assessed a set of kinematic features and the motor symptom. The ability of the method to discriminate between PD patients and HE subjects and the test-retest reliability of the computed scores were also evaluated. Computed scores correlated well with mean visual ratings of individual kinematic features. The best performing classifier (Multilayer Perceptron) classified the motor symptom (bradykinesia or dyskinesia) with an accuracy of 84% and area under the receiver operating characteristics curve of 0.86 in relation to visual classifications of the raters. In addition, the method provided high discriminating power when distinguishing between PD patients and HE subjects as well as had good test-retest reliability. This study demonstrated the potential of using digital spiral analysis for objective quantification of PD-specific and/or treatment-induced motor symptoms.
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| 3. |
- Memedi, Mevludin, et al.
(author)
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Validity and responsiveness of at-home touch-screen assessments in advanced Parkinson's disease
- 2015
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In: IEEE journal of biomedical and health informatics. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-2194 .- 2168-2208. ; 19:6, s. 1829-1834
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.
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| 4. |
- Pozzoli, Susanna, et al.
(author)
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Domain expertise–agnostic feature selection for the analysis of breast cancer data*
- 2020
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In: Artificial Intelligence in Medicine. - : Elsevier B.V.. - 0933-3657 .- 1873-2860. ; 108
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Journal article (peer-reviewed)abstract
- Progress in proteomics has enabled biologists to accurately measure the amount of protein in a tumor. This work is based on a breast cancer data set, result of the proteomics analysis of a cohort of tumors carried out at Karolinska Institutet. While evidence suggests that an anomaly in the protein content is related to the cancerous nature of tumors, the proteins that could be markers of cancer types and subtypes and the underlying interactions are not completely known. This work sheds light on the potential of the application of unsupervised learning in the analysis of the aforementioned data sets, namely in the detection of distinctive proteins for the identification of the cancer subtypes, in the absence of domain expertise. In the analyzed data set, the number of samples, or tumors, is significantly lower than the number of features, or proteins; consequently, the input data can be thought of as high-dimensional data. The use of high-dimensional data has already become widespread, and a great deal of effort has been put into high-dimensional data analysis by means of feature selection, but it is still largely based on prior specialist knowledge, which in this case is not complete. There is a growing need for unsupervised feature selection, which raises the issue of how to generate promising subsets of features among all the possible combinations, as well as how to evaluate the quality of these subsets in the absence of specialist knowledge. We hereby propose a new wrapper method for the generation and evaluation of subsets of features via spectral clustering and modularity, respectively. We conduct experiments to test the effectiveness of the new method in the analysis of the breast cancer data, in a domain expertise–agnostic context. Furthermore, we show that we can successfully augment our method by incorporating an external source of data on known protein complexes. Our approach reveals a large number of subsets of features that are better at clustering the samples than the state-of-the-art classification in terms of modularity and shows a potential to be useful for future proteomics research.
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| 5. |
- Lindeberg, Tony, 1964-, et al.
(author)
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Analysis of brain activation patterns using a 3-D scale-space primal sketch
- 1999
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In: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 7:3, s. 166-94
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Journal article (peer-reviewed)abstract
- A fundamental problem in brain imaging concerns how to define functional areas consisting of neurons that are activated together as populations. We propose that this issue can be ideally addressed by a computer vision tool referred to as the scale-space primal sketch. This concept has the attractive properties that it allows for automatic and simultaneous extraction of the spatial extent and the significance of regions with locally high activity. In addition, a hierarchical nested tree structure of activated regions and subregions is obtained. The subject in this article is to show how the scale-space primal sketch can be used for automatic determination of the spatial extent and the significance of rCBF changes. Experiments show the result of applying this approach to functional PET data, including a preliminary comparison with two more traditional clustering techniques. Compared to previous approaches, the method overcomes the limitations of performing the analysis at a single scale or assuming specific models of the data.
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| 6. |
- Roland, P, et al.
(author)
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A database generator for human brain imaging
- 2001
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In: TINS - Trends in Neurosciences. - 0166-2236 .- 1878-108X. ; 24:10, s. 562-564
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Journal article (peer-reviewed)abstract
- Sharing scientific data containing complex information requires new concepts and new technology. NEUROGENERATOR is a database generator for the neuroimaging community. A database generator is a database that generates new databases. The scientists submit raw PET and fMRI data to NEUROGENERATOR, which then processes the data in a uniform way to create databases of homogenous data suitable for data sharing, met-analysis and modelling the human brain at the systems level. These databases are then distributed to the scientists.
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| 7. |
- Ciric, Rastko, et al.
(author)
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TemplateFlow: FAIR-sharing of multi-scale, multi-species brain models.
- 2022
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In: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 19:12, s. 1568-1571
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Journal article (peer-reviewed)abstract
- Reference anatomies of the brain ('templates') and corresponding atlases are the foundation for reporting standardized neuroimaging results. Currently, there is no registry of templates and atlases; therefore, the redistribution of these resources occurs either bundled within existing software or in ad hoc ways such as downloads from institutional sites and general-purpose data repositories. We introduce TemplateFlow as a publicly available framework for human and non-human brain models. The framework combines an open database with software for access, management, and vetting, allowing scientists to share their resources under FAIR-findable, accessible, interoperable, and reusable-principles. TemplateFlow enables multifaceted insights into brains across species, and supports multiverse analyses testing whether results generalize across standard references, scales, and in the long term, species.
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| 8. |
- Norinder, Ulf, 1956-, et al.
(author)
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Conformal prediction to define applicability domain : A case study on predicting ER and AR binding
- 2016
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In: SAR and QSAR in environmental research (Print). - : Taylor & Francis. - 1062-936X .- 1029-046X. ; 27:4, s. 303-316
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Journal article (peer-reviewed)abstract
- A fundamental element when deriving a robust and predictive in silico model is not only the statistical quality of the model in question but, equally important, the estimate of its predictive boundaries. This work presents a new method, conformal prediction, for applicability domain estimation in the field of endocrine disruptors. The method is applied to binders and non-binders related to the oestrogen and androgen receptors. Ensembles of decision trees are used as statistical method and three different sets (dragon, rdkit and signature fingerprints) are investigated as chemical descriptors. The conformal prediction method results in valid models where there is an excellent balance in quality between the internally validated training set and the corresponding external test set, both in terms of validity and with respect to sensitivity and specificity. With this method the level of confidence can be readily altered by the user and the consequences thereof immediately inspected. Furthermore, the predictive boundaries for the derived models are rigorously defined by using the conformal prediction framework, thus no ambiguity exists as to the level of similarity needed for new compounds to be in or out of the predictive boundaries of the derived models where reliable predictions can be expected.
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| 9. |
- Javeed, Ashir, 1989-, et al.
(author)
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Decision Support System for Predicting Mortality in Cardiac Patients Based on Machine Learning
- 2023
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In: Applied Sciences. - : MDPI. - 2076-3417. ; 13:8
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Journal article (peer-reviewed)abstract
- Researchers have proposed several automated diagnostic systems based on machine learning and data mining techniques to predict heart failure. However, researchers have not paid close attention to predicting cardiac patient mortality. We developed a clinical decision support system for predicting mortality in cardiac patients to address this problem. The dataset collected for the experimental purposes of the proposed model consisted of 55 features with a total of 368 samples. We found that the classes in the dataset were highly imbalanced. To avoid the problem of bias in the machine learning model, we used the synthetic minority oversampling technique (SMOTE). After balancing the classes in the dataset, the newly proposed system employed a (Formula presented.) statistical model to rank the features from the dataset. The highest-ranked features were fed into an optimized random forest (RF) model for classification. The hyperparameters of the RF classifier were optimized using a grid search algorithm. The performance of the newly proposed model ((Formula presented.) _RF) was validated using several evaluation measures, including accuracy, sensitivity, specificity, F1 score, and a receiver operating characteristic (ROC) curve. With only 10 features from the dataset, the proposed model (Formula presented.) _RF achieved the highest accuracy of 94.59%. The proposed model (Formula presented.) _RF improved the performance of the standard RF model by 5.5%. Moreover, the proposed model (Formula presented.) _RF was compared with other state-of-the-art machine learning models. The experimental results show that the newly proposed decision support system outperforms the other machine learning systems using the same feature selection module ((Formula presented.)).
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| 10. |
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- 2019
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Journal article (peer-reviewed)
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