Isoform-level gene signature improves prognostic stratification and accurately classifies glioblastoma subtypes.

Molecular stratification of tumors is essential for developing personalized therapies. Although patient stratification strategies have been successful; computational methods to accurately translate the gene-signature from high-throughput platform to a clinically adaptable low-dimensional platform are currently lacking. Here, we describe PIGExClass (platform-independent isoform-level gene-expression based classification-system), a novel computational approach to derive and then transfer gene-signatures from one analytical platform to another. We applied PIGExClass to design a reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) based molecular-subtyping assay for glioblastoma multiforme (GBM), the most aggressive primary brain tumors. Unsupervised clustering of TCGA (the Cancer Genome Altas Consortium) GBM samples, based on isoform-level gene-expression profiles, recaptured the four known molecular subgroups but switched the subtype for 19% of the samples, resulting in significant (P = 0.0103) survival differences among the refined subgroups. PIGExClass derived four-class classifier, which requires only 121 transcript-variants, assigns GBM patients' molecular subtype with 92% accuracy. This classifier was translated to an RT-qPCR assay and validated in an independent cohort of 206 GBM samples. Our results demonstrate the efficacy of PIGExClass in the design of clinically adaptable molecular subtyping assay and have implications for developing robust diagnostic assays for cancer patient stratification

Quantifying sleep architecture dynamics and individual differences using big data and Bayesian networks

The pattern of sleep stages across a night (sleep architecture) is influenced by biological, behavioral, and clinical variables. However, traditional measures of sleep architecture such as stage proportions, fail to capture sleep dynamics. Here we quantify the impact of individual differences on the dynamics of sleep architecture and determine which factors or set of factors best predict the next sleep stage from current stage information. We investigated the influence of age, sex, body mass index, time of day, and sleep time on static (e.g. minutes in stage, sleep efficiency) and dynamic measures of sleep architecture (e.g. transition probabilities and stage duration distributions) using a large dataset of 3202 nights from a non-clinical population. Multi-level regressions show that sex effects duration of all Non-Rapid Eye Movement (NREM) stages, and age has a curvilinear relationship for Wake After Sleep Onset (WASO) and slow wave sleep (SWS) minutes. Bayesian network modeling reveals sleep architecture depends on time of day, total sleep time, age and sex, but not BMI. Older adults, and particularly males, have shorter bouts (more fragmentation) of Stage 2, SWS, and they transition less frequently to these stages. Additionally, we showed that the next sleep stage and its duration can be optimally predicted by the prior 2 stages and age. Our results demonstrate the potential benefit of big data and Bayesian network approaches in quantifying static and dynamic architecture of normal sleep

Predicting Pancreatic Cancer Using Support Vector Machine

This report presents an approach to predict pancreatic cancer using Support Vector Machine Classification algorithm. The research objective of this project it to predict pancreatic cancer on just genomic, just clinical and combination of genomic and clinical data. We have used real genomic data having 22,763 samples and 154 features per sample. We have also created Synthetic Clinical data having 400 samples and 7 features per sample in order to predict accuracy of just clinical data. To validate the hypothesis, we have combined synthetic clinical data with subset of features from real genomic data. In our results, we observed that prediction accuracy, precision, recall with just genomic data is 80.77%, 20%, 4%. Prediction accuracy, precision, recall with just synthetic clinical data is 93.33%, 95%, 30%. While prediction accuracy, precision, recall for combination of real genomic and synthetic clinical data is 90.83%, 10%, 5%. The combination of real genomic and synthetic clinical data decreased the accuracy since the genomic data is weakly correlated. Thus we conclude that the combination of genomic and clinical data does not improve pancreatic cancer prediction accuracy. A dataset with more significant genomic features might help to predict pancreatic cancer more accurately

Gene Expression based Survival Prediction for Cancer Patients: A Topic Modeling Approach

Cancer is one of the leading cause of death, worldwide. Many believe that genomic data will enable us to better predict the survival time of these patients, which will lead to better, more personalized treatment options and patient care. As standard survival prediction models have a hard time coping with the high-dimensionality of such gene expression (GE) data, many projects use some dimensionality reduction techniques to overcome this hurdle. We introduce a novel methodology, inspired by topic modeling from the natural language domain, to derive expressive features from the high-dimensional GE data. There, a document is represented as a mixture over a relatively small number of topics, where each topic corresponds to a distribution over the words; here, to accommodate the heterogeneity of a patient's cancer, we represent each patient (~document) as a mixture over cancer-topics, where each cancer-topic is a mixture over GE values (~words). This required some extensions to the standard LDA model eg: to accommodate the "real-valued" expression values - leading to our novel "discretized" Latent Dirichlet Allocation (dLDA) procedure. We initially focus on the METABRIC dataset, which describes breast cancer patients using the r=49,576 GE values, from microarrays. Our results show that our approach provides survival estimates that are more accurate than standard models, in terms of the standard Concordance measure. We then validate this approach by running it on the Pan-kidney (KIPAN) dataset, over r=15,529 GE values - here using the mRNAseq modality - and find that it again achieves excellent results. In both cases, we also show that the resulting model is calibrated, using the recent "D-calibrated" measure. These successes, in two different cancer types and expression modalities, demonstrates the generality, and the effectiveness, of this approach

Massively-Parallel Feature Selection for Big Data

We present the Parallel, Forward-Backward with Pruning (PFBP) algorithm for feature selection (FS) in Big Data settings (high dimensionality and/or sample size). To tackle the challenges of Big Data FS PFBP partitions the data matrix both in terms of rows (samples, training examples) as well as columns (features). By employing the concepts of $p$-values of conditional independence tests and meta-analysis techniques PFBP manages to rely only on computations local to a partition while minimizing communication costs. Then, it employs powerful and safe (asymptotically sound) heuristics to make early, approximate decisions, such as Early Dropping of features from consideration in subsequent iterations, Early Stopping of consideration of features within the same iteration, or Early Return of the winner in each iteration. PFBP provides asymptotic guarantees of optimality for data distributions faithfully representable by a causal network (Bayesian network or maximal ancestral graph). Our empirical analysis confirms a super-linear speedup of the algorithm with increasing sample size, linear scalability with respect to the number of features and processing cores, while dominating other competitive algorithms in its class