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Liver is the most common site where metastatic lesions of colorectal cancer (CRC) arise. Although researches have shown mutations in driver genes, copy number variations (CNV) and alterations in relevant signaling pathways promoted the tumor evolution and immune escape during colorectal liver metastasis (CLM), the underlying mechanism remains largely elusive. Tumor and matched metastatic tissues were collected from 16 patients diagnosed with colorectal cancer and subjected to whole-exome sequencing (WES) and RNA sequencing (RNA-seq) for studying colorectal cancer clonal evolution and immune escape during CLM. Shared somatic mutations between primary and metastatic tissues with a commonly observed subclonal-clonal (S-C) changing pattern indicated a common clonal origin between two lesions. The recurrent mutations with S-C changing pattern included those in KRAS, SYNE1, CACNA1H, PCLO, FBXL2, and DNAH11. The main CNV events underwent clonal-clonal evolution (20q amplification (amp), 17p deletion (del), 18q del and 8p del), subclonal-clonal evolution (8q amp, 13q amp, 8p del) and metastasis-specific evolution (8q amp) during the process of CLM. In addition, we revealed a potential mechanism of tumor cell immune escape by analyzing human leukocytes antigens (HLA) related clonal neoantigens and immune cell components in CLM. Our study proposed a novel liver metastasis-related evolutionary process in colorectal cancer and emphasized the theory of neo-immune escape in colorectal liver metastasis.

Sanger sequencing of candidate SNVs and Indels. (DOC 417 kb)

Quality metrics generated using YH genome sequencing data. (DOC 18.4 kb)

BACKGROUND Noninvasive prenatal detection of common fetal aneuploidies with cell-free DNA from maternal plasma has been achieved with high-throughput next-generation sequencing platforms. Turnaround times for previously tested platforms are still unsatisfactory for clinical applications, however, because of the time spent on sequencing. The development of semiconductor sequencing technology has provided a way to shorten overall run times. We studied the feasibility of using semiconductor sequencing technology for the noninvasive detection of fetal aneuploidy. METHODS Maternal plasma DNA from 13 pregnant women, corresponding to 4 euploid, 6 trisomy 21 (T21), 2 trisomy 18 (T18), and 1 trisomy 13 (T13) pregnancies, were sequenced on the Ion Torrent Personal Genome Machine sequencer platform with 318 chips. The data were analyzed with the T statistic method after correcting for GC bias, and the T value was calculated as an indicator of fetal aneuploidy. RESULTS We obtained a mean of 3 524 401 high-quality reads per sample, with an efficiency rate of 77.9%. All of the T21, T13, and T18 fetuses could be clearly distinguished from euploid fetuses, and the time spent on library preparation and sequencing was 24 h. CONCLUSIONS Semiconductor sequencing represents a suitable technology for the noninvasive prenatal detection of fetal aneuploidy. With this platform, sequencing times can be substantially reduced; however, a further larger-scale study is needed to determine the imprecision of noninvasive fetal aneuploidy detection with this system.

Strong coupling between discrete phonon and continuous electron-hole pair excitations can give rise to a pronounced asymmetry in the phonon line shape, known as the Fano resonance. This effect has been observed in a variety of systems, such as stripe-phase nickelates, graphene and high-$T_{c}$ superconductors. Here, we reveal explicit evidence for strong coupling between an infrared-active $A_1$ phonon and electronic transitions near the Weyl points (Weyl fermions) through the observation of a Fano resonance in the recently discovered Weyl semimetal TaAs. The resultant asymmetry in the phonon line shape, conspicuous at low temperatures, diminishes continuously as the temperature increases. This anomalous behavior originates from the suppression of the electronic transitions near the Weyl points due to the decreasing occupation of electronic states below the Fermi level ($E_{F}$) with increasing temperature, as well as Pauli blocking caused by thermally excited electrons above $E_{F}$. Our findings not only elucidate the underlying mechanism governing the tunable Fano resonance, but also open a new route for exploring exotic physical phenomena through the properties of phonons in Weyl semimetals., Comment: 16 pages, 3 figures

e15012Background: Microsatellite instability-High(MSI-H) or mismatch repair protein deficiency (dMMR) is a biomarker to predict immunotherapy response, which is approved by the US Food and Drug Adm...

We acquired more than 4 million useful sequences using a high-throughput method from a library for miRNA identification, which is constructed from a mixture of 14 RNA samples from different developmental stages. We mapped 247,410 reads to known silkworm miRNAs in miRBase (13.0), 701,913 reads to other RNA molecules based on sequence homology, and 3,219,395 reads to the silkworm genome. Our analysis identified 54 silkworm known miRNAs. A striking strand bias between miRNAs and their corresponding miRNA*s was found, and was speculated to reflect that transcripts from the passenger strand of pre-miRNAs may have important biological roles. Using an elaborate screening protocol, we predicted 287 candidate novel miRNAs (represent 116,494 short reads), and 59 of them have both miRNA and miRNA* sequences. Most of the previously identified silkworm miRNAs are cross-species conserved with a high abundance, while those predicted candidates tend to be species-specific miRNAs. Our discovery of SNPs among miRNAs implied within-species functional diversity. Target prediction uncovers that considerable silkworm miRNAs may aim at modulating more than one hormone signaling pathway components and/or hormone biosynthesis-related proteins implying their important roles in silkworm development.

Background The identification of causative mutations is important for treatment decisions and genetic counseling of patients with disorders of sex development (DSD). Here, we designed a new assay based on targeted next-generation sequencing (NGS) to diagnose these genetically heterogeneous disorders. Methods All coding regions and flanking sequences of 219 genes implicated in DSD were designed to be included on a panel. A total of 45 samples were used for sex chromosome dosage validation by targeted sequencing using the NGS platform. Among these, 21 samples were processed to find the causative mutation. Results The sex chromosome dosages of all 45 samples in this assay were concordant with their corresponding karyotyping results. Among the 21 DSD patients, a total of 11 mutations in SRY, NR0B1, AR, CYP17A1, GK, CHD7, and SRD5A2 were identified, including five single nucleotide variants, three InDels, one in-frame duplication, one SRY-positive 46,XX, and one gross duplication with an estimated size of more than 427,038 bp containing NR0B1 and GK. We also identified six novel mutations: c.230_231insA in SRY, c.7389delA in CHD7, c.273C>G in NR0B1, and c.2158G>A, c.1825A>G, and c.2057_2065dupTGTGTGCTG in AR. Conclusions Our assay was able to make a genetic diagnosis for eight DSD patients (38.1 %), and identified variants of uncertain clinical significance in the other three cases (14.3 %). Targeted NGS is therefore a comprehensive and efficient method to diagnose DSD. This work also expands the pathogenic mutation spectrum of DSD. Electronic supplementary material The online version of this article (doi:10.1186/s12881-016-0286-2) contains supplementary material, which is available to authorized users.

In power system, data acquisition plays an increasing important role in the field of modern power quality monitoring system. However, data communication expanding range of protocols, increasing the signal type, growing the supervisory instruments has become the major problem. In this paper, we present a power data acquisition and quality monitoring framework (F-PDAQM) that is a software framework which abstracts the most common attributes and behaviors in power quality monitoring system. F-PDAQM was developed in object-oriented with some design patterns, and implemented by using C++. It can achieve data visualization of power system via combining virtualization technology and power quality monitoring system. A significant contribution which F-PDAQM brings is that the problem of multiple communication protocols match with a variety of communication channel is solved. A voltage prediction component is provided to realize the voltage quality prediction. In addition, we propose a new concept of soft data acquisition and provide interfaces which are conducive to realize different algorithms. Soft data acquisition is an extremely important method to assure data integrity. F-PDAQM is composed of four layers. This four-layer architecture is designed for extensibility and reusability so that more complex power system problems can be tackled within the framework. It is complementary and compatible of the international standard of the power system-IEC 61850. The research in this paper has been applied to a data acquisition and supervisory system for a substation which demonstrates the validity and flexibility of the framework.

Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report a genome assembly for an elite variety (Khalas), which is 605.4 Mb in size and covers >90% of the genome (~671 Mb) and >96% of its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. dactylifera experienced a clear genome-wide duplication after either ancient whole genome duplications or massive segmental duplications. Genetic diversity analysis indicates that its stress resistance and sugar metabolism-related genes tend to be enriched in the chromosomal regions where the density of single-nucleotide polymorphisms is relatively low. Using transcriptomic data, we also illustrate the date palm’s unique sugar metabolism that underlies fruit development and ripening. Our large-scale genomic and transcriptomic data pave the way for further genomic studies not only on P. dactylifera but also other Arecaceae plants., The date palm is one of the most economically important plants of the palm family. Here, the authors present a high-quality genome assembly of the date palm Phoenix dactylifera, and reveal insights into the unique sugar metabolism underlying fruit ripening.

Regulator of exopolysaccharide and type III secretion (RetS) is a hybrid sensor kinase/response regulator protein located on bacterial membrane, and essential for expression of numerous genes. In Pseudomonas aeruginosa, RetS modulates the phosphorylation state of another kinase GacS via a direct interaction.The goal of this study is to study the effect of retS on the antibiotic 2,4-diacetyl-phloroglucinol (2,4-DAPG) production in P. fluorescens 2P24.Production of 2,4-DAPG in strain 2P24 and its mutants was quantified by HPLC. To determine the effect of RetS on the Gac/Rsm pathway, the promoters of the small RNA genes rsmX/rsmY/rsmZ and regulatory genes rsmA/rsmE in the Rsm pathway were fused with a promoterless lacZ, and the promoter activities were measured in 2P24 and the retS-deficient mutants.Genetic inactivation of the retS in strain 2P24 increased the production of an uncharacterized red pigment and the antibiotic 2,4-DAPG. RetS negatively regulated the transcription of the small RNAs RsmX and RsmZ. In the retS and gacS double mutant or the retS and gacA double mutant, all the phenotypic changes caused by the retS deletion were reversed to the level of gacS or gacA single gene mutant.In P. fluorescens 2P24, RetS negatively regulates the production of antibiotic 2,4-DAPG through the Gac/Rsm pathway.

Pseudomonas fluorescens 2P24 is an effective biocontrol agent for soil-borne plant diseases caused by microbial pathogens. The PcoI/PcoR quorum-sensing system, which influences the colonization ability of 2P24 on wheat rhizosphere, is an important factor for disease suppression. In this study we performed random mutagenesis to screen novel regulators of the pcoI gene, a biosynthase gene responsible for N-acyl-homoserine lactone (AHL) production.A gacA gene mutant carrying a pcoI-lacZ fusion was employed as the reporter strain and subjected to a random mini-Tn5 insertion mutagenesis. Expression of pcol kept at a low level under the gacA(-) negative background. The Tn5-mutants with increased pcoI transcription were selected.Two mutants with significantly increased pcoI expression were identified from approximately 10000 Tn5-inserted colonies. The interrupted locus in the mutants was identified as the mvaT gene, a global regulator belonging to the H-NS family. A homolog of the mvaT gene, named mvaV, was also found in the genome draft sequence of 2P24. Genetic inactivation of mvaT or mvaV gene resulted in increased transcription of pcoI and the production of AHL molecules. Further qutitification by HPLC showed that the 2,4-diacetylphloroglucinol (2, 4-DAPG) levels in culture supernatant of the mvaT and mvaV mutants were significantly lower than that of the wild type strain. Furthermore, the mvaT or mvaV mutation drastically improved biofilm formation in 2P24.MvaT and MvaV may function as an important regulatory complex controlling biocontrol capacity of P. fluorescens 2P24.

Bacillus thuringiensis ( B . thuringiensis ) is a soil-dwelling Gram-positive bacterium and its plasmid-encoded toxins (Cry) are commonly used as biological alternatives to pesticides. In a pangenomic study, we sequenced seven B . thuringiensis isolates in both high coverage and base-quality using the next-generation sequencing platform. The B . thuringiensis pangenome was extrapolated to have 4196 core genes and an asymptotic value of 558 unique genes when a new genome is added. Compared to the pangenomes of its closely related species of the same genus, B . thuringiensis pangenome shows an open characteristic, similar to B. cereus but not to B. anthracis ; the latter has a closed pangenome. We also found extensive divergence among the seven B . thuringiensis genome assemblies, which harbor ample repeats and single nucleotide polymorphisms (SNPs). The identities among orthologous genes are greater than 84.5% and the hotspots for the genome variations were discovered in genomic regions of 2.3–2.8 Mb and 5.0–5.6 Mb. We concluded that high-coverage sequence assemblies from multiple strains, before all the gaps are closed, are very useful for pangenomic studies.