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- Karlsson, Isak, 1987-
(författare)
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Order in the random forest
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In many domains, repeated measurements are systematically collected to obtain the characteristics of objects or situations that evolve over time or other logical orderings. Although the classification of such data series shares many similarities with traditional multidimensional classification, inducing accurate machine learning models using traditional algorithms are typically infeasible since the order of the values must be considered.In this thesis, the challenges related to inducing predictive models from data series using a class of algorithms known as random forests are studied for the purpose of efficiently and effectively classifying (i) univariate, (ii) multivariate and (iii) heterogeneous data series either directly in their sequential form or indirectly as transformed to sparse and high-dimensional representations. In the thesis, methods are developed to address the challenges of (a) handling sparse and high-dimensional data, (b) data series classification and (c) early time series classification using random forests. The proposed algorithms are empirically evaluated in large-scale experiments and practically evaluated in the context of detecting adverse drug events.In the first part of the thesis, it is demonstrated that minor modifications to the random forest algorithm and the use of a random projection technique can improve the effectiveness of random forests when faced with discrete data series projected to sparse and high-dimensional representations. In the second part of the thesis, an algorithm for inducing random forests directly from univariate, multivariate and heterogeneous data series using phase-independent patterns is introduced and shown to be highly effective in terms of both computational and predictive performance. Then, leveraging the notion of phase-independent patterns, the random forest is extended to allow for early classification of time series and is shown to perform favorably when compared to alternatives. The conclusions of the thesis not only reaffirm the empirical effectiveness of random forests for traditional multidimensional data but also indicate that the random forest framework can, with success, be extended to sequential data representations.
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| 2. |
- Levels, Johannes HM, et al.
(författare)
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High-density Lipoprotein proteome dynamics in human endotoxemia
- 2011
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Ingår i: Proteome Science. - : BiOMed Central. - 1477-5956. ; 9:34
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Tidskriftsartikel (refereegranskat)abstract
- Background: A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL) and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS) was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L) and 10 men with high HDL cholesterol levels (1.9+/-0.4mmol/L) were challenged with endotoxin (LPS) intravenously (1ng/kg bodyweight). We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome.Results: Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value<0.05) were observed in the proteome in both study groups. These changes were observed 1 hour after LPS infusion and sustained up to 24 hours, but unexpectedly were not different between the 2 study groups. Hierarchical clustering of the protein spectra at all time points of all individuals revealed 3 distinct clusters, which were largely independent of baseline HDL cholesterol levels but correlated with paraoxonase 1 activity. The acute phase protein serum amyloid A-1/2 (SAA-1/2) was clearly upregulated after LPS infusion in both groups and comprised both native and N-terminal truncated variants that were identified by two-dimensional gel electrophoresis and mass spectrometry. Individuals of one of the clusters were distinguished by a lower SAA-1/2 response after LPS challenge and a delayed time-response of the truncated variants.Conclusions: This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS.
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| 3. |
- Seçilmiş, Deniz, 1991-
(författare)
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Improving the accuracy of gene regulatory network inference from noisy data
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gene regulatory networks (GRNs) control physiological and pathological processes in a living organism, and their accurate inference from measured gene expression can identify therapeutic mechanisms for complex diseases such as cancers. The biggest obstacle in achieving the accurate reconstruction of GRNs is called ‘noise’, which considerably alters the measured gene expression because the noise generally dominates the biological signal. This situation needs to be addressed carefully so that GRN inference methods do not estimate a fit to the noise instead of the underlying biological signal. Potential noise compensation approaches are a must if the goal is to reconstruct the true system. To this end, within the scope of this doctoral thesis, I developed two methods that, in different ways, overcome the obstacles introduced by noise in gene expression data. Method 1 allows the collection of more informative subsets of genes whose expression is not as highly affected as those which cause the system to be overall uninformative. Method 2 infers a perturbation design that is better suited to the gene expression data than the originally intended design, and therefore produces more accurate GRNs at high noise levels. Furthermore, a benchmark study was carried out which compares the methodological backgrounds of GRN inference methods in terms of whether they utilize knowledge of the perturbation design or not, which clearly shows that utilization of the perturbation design is essential for accurate inference of GRNs. Finally a method is presented to improve GRN inference accuracy by selecting the GRN with the optimal sparsity based on information theoretical criteria. The three new methods (PAPERS I, II and IV) can also be used together, which is shown in this thesis to improve the GRN inference accuracy considerably more than the methods separately. As inference of accurate GRNs is a major challenge in gene regulation, the methods presented in this thesis represent an important contribution to move the field forward.
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