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Biomedical subjects

B Dolenko

Publications and source records attributed to B Dolenko.

8 recordsLinked to original sources

Class prediction and discovery using gene microarray and proteomics mass spectroscopy data: curses, caveats, cautions.

MOTIVATION: Two practical realities constrain the analysis of microarray data, mass spectra from proteomics, and biomedical infrared or magnetic resonance spectra. One is the 'curse of dimensionality': the number of features characterizing these data is in the thousands or tens of thousands. The other is the 'curse of dataset sparsity': the number of samples is limited. The consequences of these two curses are far-reaching when such data are used to classify the presence or absence of disease. RESULTS: Using very simple classifiers, we show for several publicly available microarray and proteomics datasets how these curses influence classification outcomes. In particular, even if the sample per feature ratio is increased to the recommended 5-10 by feature extraction/reduction methods, dataset sparsity can render any classification result statistically suspect. In addition, several 'optimal' feature sets are typically identifiable for sparse datasets, all producing perfect classification results, both for the training and independent validation sets. This non-uniqueness leads to interpretational difficulties and casts doubt on the biological relevance of any of these 'optimal' feature sets. We suggest an approach to assess the relative quality of apparently equally good classifiers.

Algorithms↗

Disease pattern recognition testing for rheumatoid arthritis using infrared spectra of human serum.

BACKGROUND: In view of the importance of the diagnosis of rheumatoid arthritis, a novel diagnostic method based on spectroscopic pattern recognition in combination with laboratory parameters such as the rheumatoid factor is described in the paper. Results of a diagnostic study of rheumatoid arthritis employing this method are presented. METHOD: The method uses classification of infrared (IR) spectra of serum samples by means of discriminant analysis. The spectroscopic pattern yielding the highest discriminatory power is found through a complex optimization procedure. In the study, IR spectra of 384 serum samples have been analyzed in this fashion with the objective of differentiating between rheumatoid arthritis and healthy subjects. In addition, the method integrates results from the classification with levels of the rheumatoid factor in the sample by optimized classifier weighting, in order to enhance classification accuracy, i.e. sensitivity and specificity. RESULTS: In independent validation, sensitivity and specificity of 84% and 88%, respectively, have been obtained purely on the basis of spectra classification employing a classifier designed specifically to provide robustness. Sensitivity and specificity are improved by 1% and 6%, respectively, upon inclusion of rheumatoid factor levels. Results for less robust methods are also presented and compared to the above numbers. CONCLUSION: The discrimination between RA and healthy by means of the pattern recognition approach presented here is feasible for IR spectra of serum samples. The method is sufficiently robust to be used in a clinical setting. A particular advantage of the method is its potential use in RA diagnosis at early stages of the disease.

Adolescent↗

Diagnosis and prognosis of breast cancer by magnetic resonance spectroscopy of fine-needle aspirates analysed using a statistical classification strategy.

BACKGROUND: The aim was to develop robust classifiers to analyse magnetic resonance spectroscopy (MRS) data of fine-needle aspirates taken from breast tumours. The resulting data could provide computerized, classification-based diagnosis and prognostic indicators. METHODS: Fine-needle aspirate biopsies obtained at the time of surgery for both benign and malignant breast diseases were analysed by one-dimensional proton MRS at 8.5 Tesla. Diagnostic correlation was performed between the spectra and standard pathology reports, including the presence of vascular invasion by the primary cancer and involvement of the excised axillary lymph nodes. RESULTS: Malignant tissue was distinguished from benign lesions with an overall accuracy of 93 per cent. From the same spectra, lymph node involvement was predicted with an overall accuracy of 95 per cent, and tumour vascular invasion with an overall accuracy of 94 per cent. CONCLUSION: The pathology, nodal involvement and tumour vascular invasion were predicted by computerized statistical classification of the proton MRS spectrum from a fine-needle aspirate biopsy taken from the primary breast lesion.

Adult↗

The use of 1H magnetic resonance spectroscopy in inflammatory bowel diseases: distinguishing ulcerative colitis from Crohn's disease.

OBJECTIVES: The distinction between the two major forms of inflammatory bowel diseases (IBD), i.e., ulcerative colitis (UC) and Crohn's disease is sometimes difficult and may lead to a diagnosis of indeterminate colitis. We have used 1H magnetic resonance spectroscopy (MRS) combined with multivariate methods of spectral data analysis to differentiate UC from Crohn's disease and to evaluate normal-appearing mucosa in IBD. METHODS: Colon mucosal biopsies (45 UC and 31 Crohn's disease) were submitted to 1H MRS, and multivariate analysis was applied to distinguish the two diseases. A second study was performed to test endoscopically and histologically normal biopsies from IBD patients. A classifier was developed by training on 101 spectra (76 inflamed IBD tissues and 25 normal control tissues). The spectra of 38 biopsies obtained from endoscopically and histologically normal areas of the colons of patients with IBD were put into the validation test set. RESULTS: The classification accuracy between UC and Crohn's disease was 98.6%, with only one case of Crohn's disease and no cases of UC misclassified. The diagnostic spectral regions identified by our algorithm included those for taurine, lysine, and lipid. In the second study, the classification accuracy between normal controls and IBD was 97.9%. Only 47.4% of the endoscopically and histologically normal IBD tissue spectra were classified as true normals; 34.2% showed "abnormal" magnetic resonance spectral profiles, and the remaining 18.4% could not be classified unambiguously. CONCLUSIONS: There is a strong potential for MRS to be used in the accurate diagnosis of indeterminate colitis; it may also be sensitive in detecting preclinical inflammatory changes in the colon.

Adult↗

Classification of breast tumors by grade and steroid receptor status using pattern recognition analysis of infrared spectra.

Infrared (IR) spectroscopy applied to tissue sections yields complex spectra that provide a molecular fingerprint of the tissue. We have studied a cohort of 77 breast tumors by IR spectroscopy to develop an objective method for the assignment of grade of breast tumors. Although the major variations between spectra from different tumors were in absorptions arising from triglycerides (adipose tissue) and collagen, subtle changes in spectra could be detected that were independent of cellularity and tissue composition. Using a specific multivariate pattern recognition strategy to associate these changes in spectra with different tumor grades, we then were able to accurately reclassify tumors by grade (87% accuracy; kappa = 0.835). A similar approach allowed classification of steroid receptor status (93% accuracy; kappa = 0.852). We conclude that IR spectroscopy may have clinical utility in the objective assignment of breast tumor grade.

Breast Neoplasms↗

Computerized consensus diagnosis: a classification strategy for the robust analysis of MR spectra. I. Application to 1H spectra of thyroid neoplasms.

We introduce and apply a new classification strategy we call computerized consensus diagnosis (CCD). Its purpose is to provide robust, reliable classification of biomedical data. The strategy involves the cross-validated training of several classifiers of diverse conceptual and methodological origin on the same data, and appropriately combining their outcomes. The strategy is tested on proton magnetic resonance spectra of human thyroid biopsies, which are successfully allocated to normal or carcinoma classes. We used Linear Discriminant Analysis, a Neural Net-based method, and Genetic Programming as independent classifiers on two spectral regions, and chose the median of the six classification outcomes as the consensus. This procedure yielded 100% specificity and 100% sensitivity on the training sets, and 100% specificity and 98% sensitivity on samples of known malignancy in the test sets. We discuss the necessary steps any classification approach must take to guarantee reliability, and stress the importance of fuzziness and undecidability in robust classification.

Adenocarcinoma, Follicular↗

Near-optimal region selection for feature space reduction: novel preprocessing methods for classifying MR spectra.

We introduce a global feature extraction method specifically designed to preprocess magnetic resonance spectra of biomedical origin. Such preprocessing is essential for the accurate and reliable classification of diseases or disease stages manifest in the spectra. The new method is genetic algorithm-guided. It is compared with our enhanced version of the standard forward selection algorithm. Both seek and select optimal spectral subregions. These subregions necessarily retain spectral information, thus aiding the eventual identification of the biochemistry of disease presence and progression. The power of the methods is demonstrated on two biomedical examples: the discrimination between meningioma and astrocytoma in brain tissue biopsies, and the classification of colorectal biopsies into normal and tumour classes. Both preprocessing methods lead to classification accuracies over 97% for the two examples.

Algorithms↗

Classification of 1H MR spectra of human brain neoplasms: the influence of preprocessing and computerized consensus diagnosis on classification accuracy.

We study how classification accuracy can be improved when both different data preprocessing methods and computerized consensus diagnosis (CCD) are applied to 1H magnetic resonance (MR) spectra of astrocytomas, meningiomas, and epileptic brain tissue. The MR spectra (360 MHz, 37 degrees C) of tissue specimens (biopsies) from subjects with meningiomas (95; 26 cases), astrocytomas (74; 26 cases), and epilepsy (37; 8 cases) were preprocessed by several methods. Each data set was partitioned into training and validation sets. Robust classification was carried out via linear discriminant analysis (LDA), artificial neural nets (NN), and CCD, and the results were compared with histopathological diagnosis of the MR specimens. Normalization of the relevant spectral regions affects classification accuracy significantly. The spectra-based average three-class classification accuracies of LDA and NN increased from 81.7% (unnormalized data sets) to 89.9% (normalized). CCD increased the classification accuracy of the normalized sets to an average of 91.8%. CCD invariably decreases the fraction of unclassifiable spectra. The same trends prevail, with improved results, for case-based classification. Preprocessing the 1H MR spectra is essential for accurate and reliable classification of astrocytomas, meningiomas, and nontumorous epileptic brain tissue. CCD improves classification accuracy, with an attendant decrease in the fraction of unclassifiable spectra or cases.

Astrocytoma↗