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Biomedical subjects

Staal A Vinterbo

Publications and source records attributed to Staal A Vinterbo.

4 recordsLinked to original sources

Approximation properties of haplotype tagging.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are locations at which the genomic sequences of population members differ. Since these differences are known to follow patterns, disease association studies are facilitated by identifying SNPs that allow the unique identification of such patterns. This process, known as haplotype tagging, is formulated as a combinatorial optimization problem and analyzed in terms of complexity and approximation properties. RESULTS: It is shown that the tagging problem is NP-hard but approximable within 1 + ln((n2 - n)/2) for n haplotypes but not approximable within (1-epsilon) ln(n/2) for any epsilon > 0 unless NP subset DTIME(n(log log n)). A simple, very easily implementable algorithm that exhibits the above upper bound on solution quality is presented. This algorithm has running time O(np/2(2m-p+1)) < or = O(m(n2-n)/2) where p < or = min(n, m) for n haplotypes of size m. As we show that the approximation bound is asymptotically tight, the algorithm presented is optimal with respect to this asymptotic bound. CONCLUSION: The haplotype tagging problem is hard, but approachable with a fast, practical, and surprisingly simple algorithm that cannot be significantly improved upon on a single processor machine. Hence, significant improvement in computational efforts expended can only be expected if the computational effort is distributed and done in parallel.

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Small, fuzzy and interpretable gene expression based classifiers.

MOTIVATION: Interpretation of classification models derived from gene-expression data is usually not simple, yet it is an important aspect in the analytical process. We investigate the performance of small rule-based classifiers based on fuzzy logic in five datasets that are different in size, laboratory origin and biomedical domain. RESULTS: The classifiers resulted in rules that can be readily examined by biomedical researchers. The fuzzy-logic-based classifiers compare favorably with logistic regression in all datasets. AVAILABILITY: Prototype available upon request.

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A primer on gene expression and microarrays for machine learning researchers.

Data originating from biomedical experiments has provided machine learning researchers with an important source of motivation for developing and evaluating new algorithms. A new wave of algorithmic development has been initiated with the publication of gene expression data derived from microarrays. Microarray data analysis is particularly challenging given the large number of measurements (typically in the order of thousands) that are reported for relatively few samples (typically in the order of dozens). Many data sets are now available on the web. It is important that machine learning researchers understand how data are obtained and which assumptions are necessary in the analysis. Microarray data have the potential to cause significant impact in machine learning research, not just as a rich and realistic source of cases for testing new algorithms, as has been the UCI machine learning repository in the past decades, but also as a main motivation for their development. In this article, we briefly review the biology underlying microarrays, the process of obtaining gene expression measurements, and the rationale behind the common types of analyses involved in a microarray experiment. We outline the main challenges and reiterate critical considerations regarding the construction of supervised learning models that use this type of data. The goal of this article is to familiarize machine learning researchers with data originated from gene expression microarrays.

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An Epicurean learning approach to gene-expression data classification.

We investigate the use of perceptrons for classification of microarray data where we use two datasets that were published in [Nat. Med. 7 (6) (2001) 673] and [Science 286 (1999) 531]. The classification problem studied by Khan et al. is related to the diagnosis of small round blue cell tumours (SRBCT) of childhood which are difficult to classify both clinically and via routine histology. Golub et al. study acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). We used a simulated annealing-based method in learning a system of perceptrons, each obtained by resampling of the training set. Our results are comparable to those of Khan et al. and Golub et al., indicating that there is a role for perceptrons in the classification of tumours based on gene-expression data. We also show that it is critical to perform feature selection in this type of models, i.e. we propose a method for identifying genes that might be significant for the particular tumour types. For SRBCTs, zero error on test data has been obtained for only 13 out of 2308 genes; for the ALL/AML problem, we have zero error for 9 out of 7129 genes that are used for the classification procedure. Furthermore, we provide evidence that Epicurean-style learning and simulated annealing-based search are both essential for obtaining the best classification results.

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