ACGT: advancing clinico-genomic trials on cancer - four years of experience.

The challenges regarding seamless integration of distributed, heterogeneous and multilevel data arising in the context of contemporary, post-genomic clinical trials cannot be effectively addressed with current methodologies. An urgent need exists to access data in a uniform manner, to share information among different clinical and research centers, and to store data in secure repositories assuring the privacy of patients. Advancing Clinico-Genomic Trials (ACGT) was a European Commission funded Integrated Project that aimed at providing tools and methods to enhance the efficiency of clinical trials in the -omics era. The project, now completed after four years of work, involved the development of both a set of methodological approaches as well as tools and services and its testing in the context of real-world clinico-genomic scenarios. This paper describes the main experiences using the ACGT platform and its tools within one such scenario and highlights the very promising results obtained

Identification of novel fusion genes in lung cancer using breakpoint assembly of transcriptome sequencing data

Genomic translocation events frequently underlie cancer development through generation of gene fusions with oncogenic properties. Identification of such fusion transcripts by transcriptome sequencing might help to discover new potential therapeutic targets. We developed TRUP (Tumor-specimen suited RNA-seq Unified Pipeline) (https://github.com/ruping/TRUP), a computational approach that combines split-read and read-pair analysis with de novo assembly for the identification of chimeric transcripts in cancer specimens. We apply TRUP to RNA-seq data of different tumor types, and find it to be more sensitive than alternative tools in detecting chimeric transcripts, such as secondary rearrangements in EML4-ALK-positive lung tumors, or recurrent inactivating rearrangements affecting RASSF8

Modeling Read Counts for CNV Detection in Exome Sequencing Data

Varying depth of high-throughput sequencing reads along a chromosome makes it possible to observe copy number variants (CNVs) in a sample relative to a reference. In exome and other targeted sequencing projects, technical factors increase variation in read depth while reducing the number of observed locations, adding difficulty to the problem of identifying CNVs. We present a hidden Markov model for detecting CNVs from raw read count data, using background read depth from a control set as well as other positional covariates such as GC-content. The model, exomeCopy, is applied to a large chromosome X exome sequencing project identifying a list of large unique CNVs. CNVs predicted by the model and experimentally validated are then recovered using a cross-platform control set from publicly available exome sequencing data. Simulations show high sensitivity for detecting heterozygous and homozygous CNVs, outperforming normalization and state-of-the-art segmentation methods.

Data Science in Healthcare: Benefits, Challenges and Opportunities

The advent of digital medical data has brought an exponential increase in information available for each patient, allowing for novel knowledge generation methods to emerge. Tapping into this data brings clinical research and clinical practice closer together, as data generated in ordinary clinical practice can be used towards rapid-learning healthcare systems, continuously improving and personalizing healthcare. In this context, the recent use of Data Science technologies for healthcare is providing mutual benefits to both patients and medical professionals, improving prevention and treatment for several kinds of diseases. However, the adoption and usage of Data Science solutions for healthcare still require social capacity, knowledge and higher acceptance. The goal of this chapter is to provide an overview of needs, opportunities, recommendations and challenges of using (Big) Data Science technologies in the healthcare sector. This contribution is based on a recent whitepaper (http://www.bdva.eu/sites/default/files/Big%20Data%20Technologies%20in%20Healthcare.pdf) provided by the Big Data Value Association (BDVA) (http://www.bdva.eu/), the private counterpart to the EC to implement the BDV PPP (Big Data Value PPP) programme, which focuses on the challenges and impact that (Big) Data Science may have on the entire healthcare chain