TrAp: a Tree Approach for Fingerprinting Subclonal Tumor Composition

Revealing the clonal composition of a single tumor is essential for identifying cell subpopulations with metastatic potential in primary tumors or with resistance to therapies in metastatic tumors. Sequencing technologies provide an overview of an aggregate of numerous cells, rather than subclonal-specific quantification of aberrations such as single nucleotide variants (SNVs). Computational approaches to de-mix a single collective signal from the mixed cell population of a tumor sample into its individual components are currently not available. Herein we propose a framework for deconvolving data from a single genome-wide experiment to infer the composition, abundance and evolutionary paths of the underlying cell subpopulations of a tumor. The method is based on the plausible biological assumption that tumor progression is an evolutionary process where each individual aberration event stems from a unique subclone and is present in all its descendants subclones. We have developed an efficient algorithm (TrAp) for solving this mixture problem. In silico analyses show that TrAp correctly deconvolves mixed subpopulations when the number of subpopulations and the measurement errors are moderate. We demonstrate the applicability of the method using tumor karyotypes and somatic hypermutation datasets. We applied TrAp to SNV frequency profile from Exome-Seq experiment of a renal cell carcinoma tumor sample and compared the mutational profile of the inferred subpopulations to the mutational profiles of twenty single cells of the same tumor. Despite the large experimental noise, specific co-occurring mutations found in clones inferred by TrAp are also present in some of these single cells. Finally, we deconvolve Exome-Seq data from three distinct metastases from different body compartments of one melanoma patient and exhibit the evolutionary relationships of their subpopulations

A Comprehensive Survey of Deep Learning in Remote Sensing: Theories, Tools and Challenges for the Community

In recent years, deep learning (DL), a re-branding of neural networks (NNs), has risen to the top in numerous areas, namely computer vision (CV), speech recognition, natural language processing, etc. Whereas remote sensing (RS) possesses a number of unique challenges, primarily related to sensors and applications, inevitably RS draws from many of the same theories as CV; e.g., statistics, fusion, and machine learning, to name a few. This means that the RS community should be aware of, if not at the leading edge of, of advancements like DL. Herein, we provide the most comprehensive survey of state-of-the-art RS DL research. We also review recent new developments in the DL field that can be used in DL for RS. Namely, we focus on theories, tools and challenges for the RS community. Specifically, we focus on unsolved challenges and opportunities as it relates to (i) inadequate data sets, (ii) human-understandable solutions for modelling physical phenomena, (iii) Big Data, (iv) non-traditional heterogeneous data sources, (v) DL architectures and learning algorithms for spectral, spatial and temporal data, (vi) transfer learning, (vii) an improved theoretical understanding of DL systems, (viii) high barriers to entry, and (ix) training and optimizing the DL.Comment: 64 pages, 411 references. To appear in Journal of Applied Remote Sensin