1.
Misannotated Multi-Nucleotide Variants in Public Cancer Genomics Datasets Lead to Inaccurate Mutation Calls with Significant Implications.
Srinivasan, S, Kalinava, N, Aldana, R, Li, Z, van Hagen, S, Rodenburg, SYA, Wind-Rotolo, M, Qian, X, Sasson, AS, Tang, H, et al
Cancer research. 2021;(2):282-288
Abstract
Although next-generation sequencing is widely used in cancer to profile tumors and detect variants, most somatic variant callers used in these pipelines identify variants at the lowest possible granularity, single-nucleotide variants (SNV). As a result, multiple adjacent SNVs are called individually instead of as a multi-nucleotide variants (MNV). With this approach, the amino acid change from the individual SNV within a codon could be different from the amino acid change based on the MNV that results from combining SNV, leading to incorrect conclusions about the downstream effects of the variants. Here, we analyzed 10,383 variant call files (VCF) from the Cancer Genome Atlas (TCGA) and found 12,141 incorrectly annotated MNVs. Analysis of seven commonly mutated genes from 178 studies in cBioPortal revealed that MNVs were consistently missed in 20 of these studies, whereas they were correctly annotated in 15 more recent studies. At the BRAF V600 locus, the most common example of MNV, several public datasets reported separate BRAF V600E and BRAF V600M variants instead of a single merged V600K variant. VCFs from the TCGA Mutect2 caller were used to develop a solution to merge SNV to MNV. Our custom script used the phasing information from the SNV VCF and determined whether SNVs were at the same codon and needed to be merged into MNV before variant annotation. This study shows that institutions performing NGS sequencing for cancer genomics should incorporate the step of merging MNV as a best practice in their pipelines. SIGNIFICANCE Identification of incorrect mutation calls in TCGA, including clinically relevant BRAF V600 and KRAS G12, will influence research and potentially clinical decisions.
2.
Recent progress on the molecular breeding of Cucumis sativus L. in China.
Feng, S, Zhang, J, Mu, Z, Wang, Y, Wen, C, Wu, T, Yu, C, Li, Z, Wang, H
TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik. 2020;(5):1777-1790
Abstract
Molecular breeding of Cucumis sativus L. is based on traditional breeding techniques and modern biological breeding in China. There are opportunities for further breeding improvement by molecular design breeding and the automation of phenotyping technology using untapped sources of genetic diversity. Cucumber (Cucumis sativus L.) is an important vegetable cultivated worldwide. It bears fruits of light fragrance, and crisp texture with high nutrition. China is the largest producer and consumer of cucumber, accounting for 70% of the world's total production. With increasing consumption demand, the production of Cucurbitaceae crops has been increasing yearly. Thus, new cultivars that can produce high-quality cucumber with high yield and easy cultivation are in need. Conventional genetic breeding has played an essential role in cucumber cultivar innovation over the past decades. However, its progress is slow due to the long breeding period, and difficulty in selecting stable genetic characters or genotypes, prompting researchers to apply molecular biotechnologies in cucumber breeding. Here, we first summarize the achievements of conventional cucumber breeding such as crossing and mutagenesis, and then focus on the current status of molecular breeding of cucumber in China, including the progress and achievements on cucumber genomics, molecular mechanism underlying important agronomic traits, and also on the creation of high-quality multi-resistant germplasm resources, new variety breeding and ecological breeding. Future development trends and prospects of cucumber molecular breeding in China are also discussed.