Study design requirements for RNA sequencing-based breast cancer diagnostics

Sequencing-based molecular characterization of tumors provides information required for individualized cancer treatment. There are well-defined molecular subtypes of breast cancer that provide improved prognostication compared to routine biomarkers. However, molecular subtyping is not yet implemented in routine breast cancer care. Clinical translation is dependent on subtype prediction models providing high sensitivity and specificity. In this study we evaluate sample size and RNA-sequencing read requirements for breast cancer subtyping to facilitate rational design of translational studies. We applied subsampling to ascertain the effect of training sample size and the number of RNA sequencing reads on classification accuracy of molecular subtype and routine biomarker prediction models (unsupervised and supervised). Subtype classification accuracy improved with increasing sample size up to N = 750 (accuracy = 0.93), although with a modest improvement beyond N = 350 (accuracy = 0.92). Prediction of routine biomarkers achieved accuracy of 0.94 (ER) and 0.92 (Her2) at N = 200. Subtype classification improved with RNA-sequencing library size up to 5 million reads. Development of molecular subtyping models for cancer diagnostics requires well-designed studies. Sample size and the number of RNA sequencing reads directly influence accuracy of molecular subtyping. Results in this study provide key information for rational design of translational studies aiming to bring sequencing-based diagnostics to the clinic.NonePublishe

Identification of Topological Features in Renal Tumor Microenvironment Associated with Patient Survival

Motivation As a highly heterogeneous disease, the progression of tumor is not only achieved by unlimited growth of the tumor cells, but also supported, stimulated, and nurtured by the microenvironment around it. However, traditional qualitative and/or semi-quantitative parameters obtained by pathologist’s visual examination have very limited capability to capture this interaction between tumor and its microenvironment. With the advent of digital pathology, computerized image analysis may provide a better tumor characterization and give new insights into this problem. Results We propose a novel bioimage informatics pipeline for automatically characterizing the topological organization of different cell patterns in the tumor microenvironment. We apply this pipeline to the only publicly available large histopathology image dataset for a cohort of 190 patients with papillary renal cell carcinoma obtained from The Cancer Genome Atlas project. Experimental results show that the proposed topological features can successfully stratify early- and middle-stage patients with distinct survival, and show superior performance to traditional clinical features and cellular morphological and intensity features. The proposed features not only provide new insights into the topological organizations of cancers, but also can be integrated with genomic data in future studies to develop new integrative biomarkers

PALSAR wide-area mapping and annual monitoring methodology for Borneo

This paper describes the operational radar mapping processing chain developed and steps taken to produce a provisional wide-area PALSAR forest and land cover map of Borneo for the year 2007, compliant with emerging international standards (CEOS guidelines, FAO LCCS). The methodology is based on the classification of FBS and FBD image pairs. To cover Borneo the equivalent of 554 standard images is required. The final overall accuracy assessment result shows this demonstration map product is in 85.5% full agreement with the independent reference dataset and in 7.8% ‘partial agreement’. Monitoring land cover change on an annual basis requires consistent year-to-year mapping. This implies that the localised and temporal effects of environmental factors on the backscatter level (such as inundation or El Niño drought) and variation due to differing observation dates/cycles (related to change of season) have to be accounted for strip by strip. New concepts for (a) automated intercalibration of radar data, (b) time-consistency and (c) automated adaptation of radar signatures to changing environmental conditions have been evaluated for its usefulness to improve the classification and the consistency of annual monitoring

Study of Population Structure and Genetic Prediction of Buffalo from Different Provinces of Iran using Machine Learning Method

Considering breeding livestock programs to milk production and type traits based on existence two different ecotypes of Iranian’s buffalo, a study carried out to investigate the population structure of Iranian buffalo and validate its classification accuracy according to different ecotypes from Iran (Azerbaijan and North) using data SNP chip 90K by means Support vector Machine (SVM), Random Forest (RF) and Discriminant Analysis Principal Component (DAPC) methods. A total of 258 buffalo were sampled and genotyped. The results of admixture, multidimensional scaling (MDS), and DAPC showed a close relationship between the animals of different provinces. Two ecotypes indicated higher accuracy of 96% that the Area Under Curve (AUC) confirmed the obtained result of the SVM approach while the DAPC and RF approach demonstrated lower accuracy of 88% and 80 %, respectively. SVM method proved high accuracy compared with DAPC and RF methods and assigned animals to their herds with more accuracy. According to these results, buffaloes distributed in two different ecotypes are one breed, and therefore the same breeding program should be used in the future. The water buffalo ecotype of the northern provinces of Iran and Azerbaijan seem to belong to the same population

Deep learning cardiac motion analysis for human survival prediction

Motion analysis is used in computer vision to understand the behaviour of moving objects in sequences of images. Optimising the interpretation of dynamic biological systems requires accurate and precise motion tracking as well as efficient representations of high-dimensional motion trajectories so that these can be used for prediction tasks. Here we use image sequences of the heart, acquired using cardiac magnetic resonance imaging, to create time-resolved three-dimensional segmentations using a fully convolutional network trained on anatomical shape priors. This dense motion model formed the input to a supervised denoising autoencoder (4Dsurvival), which is a hybrid network consisting of an autoencoder that learns a task-specific latent code representation trained on observed outcome data, yielding a latent representation optimised for survival prediction. To handle right-censored survival outcomes, our network used a Cox partial likelihood loss function. In a study of 302 patients the predictive accuracy (quantified by Harrell's C-index) was significantly higher (p < .0001) for our model C=0.73 (95$\%$ CI: 0.68 - 0.78) than the human benchmark of C=0.59 (95$\%$ CI: 0.53 - 0.65). This work demonstrates how a complex computer vision task using high-dimensional medical image data can efficiently predict human survival

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology