SUMMARY: Here, we present Viola, a Python package that provides structural variant (SV; large scale genome DNA variations that can result in disease, e.g. cancer) signature analytical functions and utilities for custom SV classification, merging multi-SV-caller output files and SV annotation. We demonstrate that Viola can extract biologically meaningful SV signatures from publicly available SV data for cancer and we evaluate the computational time necessary for annotation of the data. AVAILABILITY AND IMPLEMENTATION: Viola is available on pip (https://pypi.org/project/Viola-SV/) and the source code is on GitHub (https://github.com/dermasugita/Viola-SV). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: The recent success of immunotherapy in treating tumors has attracted increasing interest in research related to the adaptive immune system in the tumor microenvironment. Recent advances in next-generation sequencing technology enabled the sequencing of whole T-cell receptors (TCRs) and B-cell receptors (BCRs)/immunoglobulins (Igs) in the tumor microenvironment. Since BCRs/Igs in tumor tissues have high affinities for tumor-specific antigens, the patterns of their amino acid sequences and other sequence-independent features such as the number of somatic hypermutations (SHMs) may differ between the normal and tumor microenvironments. However, given the high diversity of BCRs/Igs and the rarity of recurrent sequences among individuals, it is far more difficult to capture such differences in BCR/Ig sequences than in TCR sequences. The aim of this study was to explore the possibility of discriminating BCRs/Igs in tumor and in normal tissues, by capturing these differences using supervised machine learning methods applied to RNA sequences of BCRs/Igs. RESULTS: RNA sequences of BCRs/Igs were obtained from matched normal and tumor specimens from 90 gastric cancer patients. BCR/Ig-features obtained in Rep-Seq were used to classify individual BCR/Ig sequences into normal or tumor classes. Different machine learning models using various features were constructed as well as gradient boosting machine (GBM) classifier combining these models. The results demonstrated that BCR/Ig sequences between normal and tumor microenvironments exhibit their differences. Next, by using a GBM trained to classify individual BCR/Ig sequences, we tried to classify sets of BCR/Ig sequences into normal or tumor classes. As a result, an area under the curve (AUC) value of 0.826 was achieved, suggesting that BCR/Ig repertoires have distinct sequence-level features in normal and tumor tissues. CONCLUSIONS: To the best of our knowledge, this is the first study to show that BCR/Ig sequences derived from tumor and normal tissues have globally distinct patterns, and that these tissues can be effectively differentiated using BCR/Ig repertoires.

Automated detection of cancer metastases in lymph nodes has the potential to improve the assessment of prognosis for patients. To enable fair comparison between the algorithms for this purpose, we set up the CAMELYON17 challenge in conjunction with the IEEE International Symposium on Biomedical Imaging 2017 Conference in Melbourne. Over 300 participants registered on the challenge website, of which 23 teams submitted a total of 37 algorithms before the initial deadline. Participants were provided with 899 whole-slide images (WSIs) for developing their algorithms. The developed algorithms were evaluated based on the test set encompassing 100 patients and 500 WSIs. The evaluation metric used was a quadratic weighted Cohen's kappa. We discuss the algorithmic details of the 10 best pre-conference and two post-conference submissions. All these participants used convolutional neural networks in combination with pre- and postprocessing steps. Algorithms differed mostly in neural network architecture, training strategy, and pre- and postprocessing methodology. Overall, the kappa metric ranged from 0.89 to -0.13 across all submissions. The best results were obtained with pre-trained architectures such as ResNet. Confusion matrix analysis revealed that all participants struggled with reliably identifying isolated tumor cells, the smallest type of metastasis, with detection rates below 40%. Qualitative inspection of the results of the top participants showed categories of false positives, such as nerves or contamination, which could be targeted for further optimization. Last, we show that simple combinations of the top algorithms result in higher kappa metric values than any algorithm individually, with 0.93 for the best combination.

Motivation: The aim of precision medicine is to harness new knowledge and technology to optimize the timing and targeting of interventions for maximal therapeutic benefit. This study explores the possibility of building AI models without precise pixel-level annotation in prediction of the tumor size, extrathyroidal extension, lymph node metastasis, cancer stage and BRAF mutation in thyroid cancer diagnosis, providing the patients' background information, histopathological and immunohistochemical tissue images. Results: A novel framework for objective evaluation of automatic patient diagnosis algorithms has been established under the auspices of the IEEE International Symposium on Biomedical Imaging 2017- A Grand Challenge for Tissue Microarray Analysis in Thyroid Cancer Diagnosis. Here, we present the datasets, methods and results of the challenge and lay down the principles for future uses of this benchmark. The main contributions of the challenge include the creation of the data repository of tissue microarrays; the creation of the clinical diagnosis classification data repository of thyroid cancer; and the definition of objective quantitative evaluation for comparison and ranking of the algorithms. With this benchmark, three automatic methods for predictions of the five clinical outcomes have been compared, and detailed quantitative evaluation results are presented in this paper. Based on the quantitative evaluation results, we believe automatic patient diagnosis is still a challenging and unsolved problem. Availability and implementation: The datasets and the evaluation software will be made available to the research community, further encouraging future developments in this field. (http://www-o.ntust.edu.tw/cvmi/ISBI2017/). Contact: [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.

In this paper, we propose a framework to make the text clustering process, as a whole, efficient. In a real text clustering task, an analyst usually has some expectation on the results in mind. However, a single run of a clustering algorithm on the preprocessed data would not satisfy the expectation. Then the analyst faces labor-intensive trials for improving the results that involve repetitive feature refinement and parameter tuning. We develop the Iterative and Interactive Metric Learning System (IIMLS) for addressing the challenge. Specifically, IIMLS allows analysts to input feedback on a current clustering result. Given the feedback, IIMLS optimizes metric in the feature space so that the clustering algorithm applied with the refined metric would reflect the feedback. As a byproduct, learned metric may be used for a similar dataset. Illustrative examples on a real-world dataset show IIMLS can dramatically improve efficiency of a text clustering task. The learned ¿knowledge¿, or the metric, is visualized for gaining insights of the optimized feature metric.

MOTIVATION: Since DNA microarray experiments provide us with huge amount of gene expression data, they should be analyzed with statistical methods to extract the meanings of experimental results. Some dimensionality reduction methods such as Principal Component Analysis (PCA) are used to roughly visualize the distribution of high dimensional gene expression data. However, in the case of binary classification of gene expression data, PCA does not utilize class information when choosing axes. Thus clearly separable data in the original space may not be so in the reduced space used in PCA. RESULTS: For visualization and class prediction of gene expression data, we have developed a new SVM-based method called multidimensional SVMs, that generate multiple orthogonal axes. This method projects high dimensional data into lower dimensional space to exhibit properties of the data clearly and to visualize a distribution of the data roughly. Furthermore, the multiple axes can be used for class prediction. The basic properties of conventional SVMs are retained in our method: solutions of mathematical programming are sparse, and nonlinear classification is implemented implicitly through the use of kernel functions. The application of our method to the experimentally obtained gene expression datasets for patients' samples indicates that our algorithm is efficient and useful for visualization and class prediction. CONTACT: [email protected].