Molecular characterization of lung adenocarcinoma from Korean patients using next generation sequencing.

The treatment of Lung adenocarcinoma (LUAD) could benefit from the incorporation of precision medicine. This study was to identify cancer-related genetic alterations by next generation sequencing (NGS) in resected LUAD samples from Korean patients and to determine their associations with clinical features. A total of 201 tumors and their matched peripheral blood samples were analyzed using targeted sequencing via the Illumina HiSeq 2500 platform of 242 genes with a median depth of coverage greater than 500X.

Brain somatic mutations observed in Alzheimer's disease associated with aging and dysregulation of tau phosphorylation.

The role of brain somatic mutations in Alzheimer's disease (AD) is not well understood. Here, we perform deep whole-exome sequencing (average read depth 584×) in 111 postmortem hippocampal formation and matched blood samples from 52 patients with AD and 11 individuals not affected by AD. The number of somatic single nucleotide variations (SNVs) in AD brain specimens increases significantly with aging, and the rate of mutation accumulation in the brain is 4.

The use of technical replication for detection of low-level somatic mutations in next-generation sequencing.

Accurate genome-wide detection of somatic mutations with low variant allele frequency (VAF, <1%) has proven difficult, for which generalized, scalable methods are lacking. Herein, we describe a new computational method, called RePlow, that we developed to detect low-VAF somatic mutations based on simple, library-level replicates for next-generation sequencing on any platform. Through joint analysis of replicates, RePlow is able to remove prevailing background errors in next-generation sequencing analysis, facilitating remarkable improvement in the detection accuracy for low-VAF somatic mutations (up to ~99% reduction in false positives).

Brain somatic mutations in cause intractable epilepsy with aberrant N-glycosylation.

Objective: To identify whether somatic mutations in alter N-glycan structures in human brain tissues and cause nonlesional focal epilepsy (NLFE) or mild malformation of cortical development (mMCD).

Methods: Deep whole exome and targeted sequencing analyses were conducted for matched brain and blood tissues from patients with intractable NLFE and patients with mMCD who are negative for mutations in mTOR pathway genes. Furthermore, tissue glyco-capture and nanoLC/mass spectrometry analysis were performed to examine N-glycosylation in affected brain tissue.

AIRVF: a filtering toolbox for precise variant calling in Ion Torrent sequencing.

Summary: Ion Torrent sequencing is one of the most frequently used platforms in healthcare research and industry. Despite many advantages, platform-specific artifacts complicate efficient separation of true variants from errors, especially in variants with lower allele frequencies (<15%). Here, we developed a multi-step filtering toolbox AIRVF that works on flowgram, raw and mapped reads and called variants to reduce artifact-driven false variant calls.

Somatic mutation driven codon transition bias in human cancer.

Accumulation of DNA mutations alters amino acid sequence in the key domains of oncoproteins, leading to cellular malignant transformation. Due to redundancy of the genetic code, the same amino acid alteration can be achieved by multiple distinct genetic mutations, which are considered functionally identical and not actively distinguished in the current cancer genome research. For the first time, we analyzed the distribution of codon level transitions acquired by somatic mutations in human cancers.

ISOexpresso: a web-based platform for isoform-level expression analysis in human cancer.

Background: Alternative splicing events that result in the production of multiple gene isoforms reveals important molecular mechanisms. Gene isoforms are often differentially expressed across organs and tissues, developmental stages, and disease conditions. Specifically, recent studies show that aberrant regulation of alternative splicing frequently occurs in cancer to affect tumor cell transformation and growth.

Vecuum: identification and filtration of false somatic variants caused by recombinant vector contamination.

Motivation: Advances in sequencing technologies have remarkably lowered the detection limit of somatic variants to a low frequency. However, calling mutations at this range is still confounded by many factors including environmental contamination. Vector contamination is a continuously occurring issue and is especially problematic since vector inserts are hardly distinguishable from the sample sequences.