This paper describes the methodology of providing multiprobability predictions for proteomic mass spectrometry data. The methodology is based on a newly developed machine learning framework called Venn machines. Is allows to output a valid probability interval. The methodology is designed for mass spectrometry data. For demonstrative purposes, we applied this methodology to MALDI-TOF data sets in order to predict the diagnosis of heart disease and early diagnoses of ovarian cancer and breast cancer. The experiments showed that probability intervals are narrow, that is, the output of the multiprobability predictor is similar to a single probability distribution. In addition, probability intervals produced for heart disease and ovarian cancer data were more accurate than the output of corresponding probability predictor. When Venn machines were forced to make point predictions, the accuracy of such predictions is for the most data better than the accuracy of the underlying algorithm that outputs single probability distribution of a label. Application of this methodology to MALDI-TOF data sets empirically demonstrates the validity. The accuracy of the proposed method on ovarian cancer data rises from 66.7 % 11 months in advance of the moment of diagnosis to up to 90.2 % at the moment of diagnosis. The same approach has been applied to heart disease data without time dependency, although the achieved accuracy was not as high (up to 69.9 %). The methodology allowed us to confirm mass spectrometry peaks previously identified as carrying statistically significant information for discrimination between controls and cases.

This paper describes the methodology of providing multiprobability predictions for proteomic mass spectrometry data. The methodology is based on a newly developed machine learning framework called Venn machines. They allow us to output a valid probability interval. We apply this methodology to mass spectrometry data sets in order to predict the diagnosis of heart disease and early diagnoses of ovarian cancer. The experiments show that probability intervals are valid and narrow. In addition, probability intervals were compared with the output of a corresponding probability predictor.

The work describes an application of a recently developed machine-learning technique called Mondrian predictors to risk assessment of ovarian and breast cancers. The analysis is based on mass spectrometry profiling of human serum samples that were collected in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. The work describes the technique and presents the results of classification (diagnosis) and the corresponding measures of confidence of the diagnostics. The main advantage of this approach is a proven validity of prediction. The work also describes an approach to improve early diagnosis of ovarian and breast cancers since the data in the United Kingdom Collaborative Trial of Ovarian Cancer Screening were collected over a period of 7 years and do allow to make observations of changes in human serum over that period of time. Significance of improvement is confirmed statistically (for up to 11 months for ovarian cancer and 9 months for breast cancer). In addition, the methodology allowed us to pinpoint the same mass spectrometry peaks as previously detected as carrying statistically significant information for discrimination between healthy and diseased patients. The results are discussed.

The paper describes an application of a recently developed machine learning technique called Mondrian predictors to risk assessment of ovarian and breast cancers. The analysis is based on mass spectrometry profiling of human serum samples that were collected in the United Kingdom Collaborative Trial of Ovarian Cancer Screening. The paper describes the technique and presents the results of classification (diagnosis) and the corresponding measures of confidence of the diagnostics. The main advantage of this approach is a proven validity of prediction. The paper also describes an approach to improve early diagnosis of ovarian and breast cancers since the data in the United Kingdom Collaborative Trial of Ovarian Cancer Screening were collected over a period of seven years and do allow to make observations of changes in human serum over that period of time. Significance of improvement is confirmed statistically (for up to 11 months for Ovarian Cancer and 9 months for Breast Cancer). In addition, the methodology allowed us to pinpoint the same mass spectrometry peaks as previously detected as carrying statistically significant information for discrimination between healthy and diseased patients. The results are discussed. 1 Computer Learning Research Centre, Royal Holloway, University of London 2 EGA Institute for Women’s Health, University College London 3 BioCentre and Department of Chemistry, University of Reading ∗ Address correspondence to Dr Ilia Nouretdinov, Department of Computer Science, Royal Holloway, University of London, Egham, Surrey TW20 0EX. Tel/Fax: +44(0)1784 443912/439786. Email: ilia@cs.rhul.ac.uk.

Aim: A nested case-control discovery study was undertaken 10 test whether information within the serum peptidome can improve on the utility of CA125 for early ovarian cancer detection. Materials and Methods: High-throughput matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) was used to profile 295 serum samples from women pre-dating their ovarian cancer diagnosis and from 585 matched control samples. Classification rules incorporating CA125 and MS peak intensities were tested for discriminating ability. Results: Two peaks were found which in combination with CA125 discriminated cases from controls up to 15 and 11 months before diagnosis, respectively, and earlier than using CA125 alone. One peak was identified as connective tissue-activating peptide III (CTAPIII), whilst the other was putatively identified as platelet factor 4 (PF4). ELISA data supported the down-regulation of PF4 in early cancer cases. Conclusion: Serum peptide information with CA125 improves lead time for early detection of ovarian cancer. The candidate markers are platelet-derived chemokines, suggesting a link between platelet function and tumour development.

Objectives: Our objective was to test the performance of CA125 in classifying serum samples from a cohort of malignant and benign ovarian cancers and age-matched healthy controls and to assess whether combining information from matrix-assisted laser desorption/ionization (MALDI) time-of-flight profiling could improve diagnostic performance.Materials and Methods: Serum samples from women with ovarian neoplasms and healthy volunteers were subjected to CA125 assay and MALDI time-of-flight mass spectrometry (MS) profiling. Models were built from training data sets using discriminatory MALDI MS peaks in combination with CA125 values and tested their ability to classify blinded test samples. These were compared with models using CA125 threshold levels from 193 patients with ovarian cancer, 290 with benign neoplasm, and 2236 postmenopausal healthy controls.Results: Using a CA125 cutoff of 30 U/mL, an overall sensitivity of 94.8% (96.6% specificity) was obtained when comparing malignancies versus healthy postmenopausal controls, whereas a cutoff of 65 U/mL provided a sensitivity of 83.9% (99.6% specificity). High classification accuracies were obtained for early-stage cancers (93.5% sensitivity). Reasons for high accuracies include recruitment bias, restriction to postmenopausal women, and inclusion of only primary invasive epithelial ovarian cancer cases. The combination of MS profiling information with CA125 did not significantly improve the specificity/accuracy compared with classifications on the basis of CA125 alone.Conclusions: We report unexpectedly good performance of serum CA125 using threshold classification in discriminating healthy controls and women with benign masses from those with invasive ovarian cancer. This highlights the dependence of diagnostic tests on the characteristics of the study population and the crucial need for authors to provide sufficient relevant details to allow comparison. Our study also shows that MS profiling information adds little to diagnostic accuracy. This finding is in contrast with other reports and shows the limitations of serum MS profiling for biomarker discovery and as a diagnostic tool.

Conformal predictors represent a new flexible framework that outputs region predictions with a guaranteed error rate. Efficiency of such predictions depends on the nonconformity measure that underlies the predictor. In this work we designed new nonconformity measures based on a random forest classifier. Experiments demonstrate that proposed conformal predictors are more efficient than current benchmarks on noisy mass spectrometry data (and at least as efficient on other type of data) while maintaining the property of validity: they output fewer multiple predictions, and the ratio of mistakes does not exceed the preset level. When forced to produce singleton predictions, the designed conformal predictors are at least as accurate as the benchmarks and sometimes significantly outperform them.

Background: The serum peptidome may be a valuable source of diagnostic cancer biomarkers. Previous mass spectrometry (MS) studies have suggested that groups of related peptides discriminatory for different cancer types are generated ex vivo from abundant serum proteins by tumor-specific exopeptidases. We tested 2 complementary serum profiling strategies to see if similar peptides could be found that discriminate ovarian cancer from benign cases and healthy controls. Methods: We subjected identically collected and processed serum samples from healthy volunteers and patients to automated polypeptide extraction on octadecylsilane-coated magnetic beads and separately on ZipTips before MALDI-TOF MS profiling at 2 centers. The 2 platforms were compared and case control profiling data analyzed to find altered MS peak intensities. We tested models built from training datasets for both methods for their ability to classify a blinded test set. Results: Both profiling platforms had CVs of approximately 15% and could be applied for high-throughput analysis of clinical samples. The 2 methods generated overlapping peptide profiles, with some differences in peak intensity in different mass regions. In cross-validation, models from training data gave diagnostic accuracies up to 87% for discriminating malignant ovarian cancer from healthy controls and up to 81% for discriminating malignant from benign samples. Diagnostic accuracies up to 71% (malignant vs healthy) and up to 65% (malignant vs benign) were obtained when the models were validated on the blinded test set. Conclusions: For ovarian cancer, altered MALDI-TOF MS peptide profiles alone cannot be used for accurate diagnoses.

In this paper we apply computer learning methods to the diagnosis of ovarian cancer using the level of the standard biomarker CA125 in conjunction with information provided by mass spectrometry. Our algorithm gives probability predictions for the disease. To check the power of our algorithm we use it to test the hypothesis that CA125 and the peaks do not contain useful information for the prediction of the disease at a particular time before the diagnosis. It produces p-values that are less than those produced by an algorithm that has been previously applied to this data set. Our conclusion is that the proposed algorithm is especially reliable for prediction the ovarian cancer on some stages.

The invention discloses a novel sun visor, and more particularly, to the combination of a sun visor and bandanna, and to the attachment mechanism, for releasably securing the headband to the visor. A sun visor includes a band of flexible, moisture absorbent material, and a sun visor brim member. The brim member is a planar self-supporting material, secured to the band by flaps. The brim is adapted to lie symmetrically curved when affixed to the head of a person by the band. The inner curved edge of the brim is positioned to lie against the forehead of the user, when affixed to the head of a person by the band. Two or three flaps are provided each of which extending inward from the curved inner edge. Each flap is provided with pairs of fasteners, preferably of the hook and loop type, that the flaps can be folded over and secured in the folded position by the fasteners, to form an elongated loop. The brim is preferably a closed cell, substantially moisture impermeable polymeric foam. The flaps are extended approximately perpendicular to a line tangent to the curve of the inner brim edge at the point of intersection of the flap inner edge and the brim inner edge.

We construct prediction intervals for the linear regression model with IID errors with a known distribution, not necessarily Gaussian. The coverage probability of our prediction intervals is equal to the nominal confidence level not only unconditionally but also conditionally given a natural sigma-algebra of invariant events. This implies, in particular, the perfect calibration of our prediction intervals in the on-line mode of prediction.

Ovarian cancer (OC) can usually clinically be diagnosed only at the late stages of the disease. We show that the combination of the biomarker antigen CA125 with proteomic mass spectra data and applying newly developed machine learning algorithms, may establish a diagnosis of OC very early.

This study aims to prove empirically that the information contained in serum proteome mass spectra can improve the discriminating ability of CA125 in early stages of ovarian cancer (OC) development. Our serial data collected in the UKCTOCS project over the period of 7 years allow us to reject the null hypothesis at significance level 5% for detection up to 15 months in advance of the diagnosis which was confirmed by histology/cytology. Moreover, in addition to what has been previously reported we identified certain mass spectrometry (MS) peaks that, in combination with CA125 level, can provide reliable long term prediction of OC. The peaks with m/z-values 7772 Da and 9297 Da were the most informative in extending the period of significant discrimination, and in combination with CA125 they proved to be able to predict the disease up to 6 and 4 months earlier than CA125 alone, respectively.