Date Published: April 12, 2017
Publisher: Public Library of Science
Author(s): Jun-Hee Yoon, Thomas W. Kim, Pedro Mendez, David M. Jablons, Il-Jin Kim, Jian-Hua Mao.
The development of next-generation sequencing (NGS) technology allows to sequence whole exomes or genome. However, data analysis is still the biggest bottleneck for its wide implementation. Most laboratories still depend on manual procedures for data handling and analyses, which translates into a delay and decreased efficiency in the delivery of NGS results to doctors and patients. Thus, there is high demand for developing an automatic and an easy-to-use NGS data analyses system. We developed comprehensive, automatic genetic analyses controller named Mobile Genome Express (MGE) that works in smartphones or other mobile devices. MGE can handle all the steps for genetic analyses, such as: sample information submission, sequencing run quality check from the sequencer, secured data transfer and results review. We sequenced an Actrometrix control DNA containing multiple proven human mutations using a targeted sequencing panel, and the whole analysis was managed by MGE, and its data reviewing program called ELECTRO. All steps were processed automatically except for the final sequencing review procedure with ELECTRO to confirm mutations. The data analysis process was completed within several hours. We confirmed the mutations that we have identified were consistent with our previous results obtained by using multi-step, manual pipelines.
There were several breakthroughs for genetic and genomic analyses since the first description of DNA double helix structure in 1953 [1,2]. A development of the polymerase chain reaction (PCR) technology opened an era for different types of genetic analyses with limited amount of DNA from various biological samples [3–5]. PCR amplification technology is still a foundation of up-to-date genome analysis technologies. Sanger sequencing was then developed [6,7], and enabled a discovery of human genome sequences and completed the human genome sequence map (The Human Genome Project) in 2003 (https://www.genome.gov/10001772). The next revolution of genetic and genomic analyses would be the development of microarray or DNA chip technology . With this hybridization-based high throughput expression or genotype technologies, all known genes could be analyzed at one time for their expression. Microarray technology contributed to the identification of new subtypes and biomarkers of diseases such as cancer [8–12].
It is highly expected that NGS sequencing information will be available to more and more people who want to know their genetic information, thanks to the significant reduction of a cost and TAT of NGS sequencing. We show that MGE can be an efficient mobile device or cell phone-based genetic controller enabling personalized genome analyses using targeted NGS panel feasible to most of regular laboratories. Current workflows in most laboratories require technicians or bioinformaticians to stay in a laboratory to check the sequencing run quality from the sequencing machine. Then data should be transferred to different types of bioinformatics pipelines used for each laboratory and analyzed by skilled bioinformaticians. All these manual-based sequencing quality check, data transfer, analyses, and review steps prevent the fast and robust genetic analyses. MGE allows us to check all the processes mentioned above into one application of a cellular phone or other mobile device. We used TMAP (Torrent Mapping Alignment Program) for mapping the raw sequencing reads and used DanPA program for variant calling and annotation. DanPA was previously tested in different sequencing projects [22, 37]. We plan to install and use another variant caller in MGE in a near future.