Deep Learning on Abnormal Chromosome Segments: An Intelligent Copy Number Variants Detection System Design

Gene testing emerged as a business in the last two decades, and the testing cost has been reduced from 100 million to 1000 dollars for the development of technologies. Preimplantation genetic screening (PGS) is a popular genetic profiling of embryos prior to implantation in gene testing. Copy number variants (CNVs) detection is a key task in PGS which still needs the manual operation and evaluation. At the same time, deep learning technology earns a booming development and wide application in recent years for its strong computing and learning capability. This research redesigns the PGS workflow with the intelligent CNVs detection system, and proposes the corresponding system framework. Deep learning is selected as the proper technology in the system design for CNVs detection, which also fit the task of denoising. The evaluation is conducted on simulation dataset with high accuracy and low time cost, which may achieve the requirements of clinical application and reduce the workload of bioinformatics experts. Moreover, the redesigned process and proposed framework may enlighten the intelligent system design for gene testing in following work, and provide a guidance of deep learning application in AI healthcar

A Tutorial on Coding Methods for DNA-based Molecular Communications and Storage

Exponential increase of data has motivated advances of data storage technologies. As a promising storage media, DeoxyriboNucleic Acid (DNA) storage provides a much higher data density and superior durability, compared with state-of-the-art media. In this paper, we provide a tutorial on DNA storage and its role in molecular communications. Firstly, we introduce fundamentals of DNA-based molecular communications and storage (MCS), discussing the basic process of performing DNA storage in MCS. Furthermore, we provide tutorials on how conventional coding schemes that are used in wireless communications can be applied to DNA-based MCS, along with numerical results. Finally, promising research directions on DNA-based data storage in molecular communications are introduced and discussed in this paper

Bayesian localization of CNV candidates in WGS data within minutes

Background: Full Bayesian inference for detecting copy number variants (CNV) from whole-genome sequencing (WGS) data is still largely infeasible due to computational demands. A recently introduced approach to perform Forward-Backward Gibbs sampling using dynamic Haar wavelet compression has alleviated issues of convergence and, to some extent, speed. Yet, the problem remains challenging in practice. Results: In this paper, we propose an improved algorithmic framework for this approach. We provide new space-efficient data structures to query sufficient statistics in logarithmic time, based on a linear-Time, in-place transform of the data, which also improves on the compression ratio. We also propose a new approach to efficiently store and update marginal state counts obtained from the Gibbs sampler. Conclusions: Using this approach, we discover several CNV candidates in two rat populations divergently selected for tame and aggressive behavior, consistent with earlier results concerning the domestication syndrome as well as experimental observations. Computationally, we observe a 29.5-fold decrease in memory, an average 5.8-fold speedup, as well as a 191-fold decrease in minor page faults. We also observe that metrics varied greatly in the old implementation, but not the new one. We conjecture that this is due to the better compression scheme. The fully Bayesian segmentation of the entire WGS data set required 3.5 min and 1.24 GB of memory, and can hence be performed on a commodity laptop

Long-term neural and physiological phenotyping of a single human

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.</p

Data based identification and prediction of nonlinear and complex dynamical systems

We thank Dr. R. Yang (formerly at ASU), Dr. R.-Q. Su (formerly at ASU), and Mr. Zhesi Shen for their contributions to a number of original papers on which this Review is partly based. This work was supported by ARO under Grant No. W911NF-14-1-0504. W.-X. Wang was also supported by NSFC under Grants No. 61573064 and No. 61074116, as well as by the Fundamental Research Funds for the Central Universities, Beijing Nova Programme.Peer reviewedPostprin