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Yuan L.,CAS Beijing Institute of Genomics | Yuan L.,Peking Union Medical College | Yuan L.,Suzhou Institute of Systems Medicine | Yu Y.,Liaoning University | And 11 more authors.
BMC Genomics | Year: 2017

Background: Next-generation sequencing (NGS) technologies have greatly promoted the genomic study of prokaryotes. However, highly fragmented assemblies due to short reads from NGS are still a limiting factor in gaining insights into the genome biology. Reference-assisted tools are promising in genome assembly, but tend to result in false assembly when the assigned reference has extensive rearrangements. Results: Herein, we present GAAP, a genome assembly pipeline for scaffolding based on core-gene-defined Genome Organizational Framework (cGOF) described in our previous study. Instead of assigning references, we use the multiple-reference-derived cGOFs as indexes to assist in order and orientation of the scaffolds and build a skeleton structure, and then use read pairs to extend scaffolds, called local scaffolding, and distinguish between true and chimeric adjacencies in the scaffolds. In our performance tests using both empirical and simulated data of 15 genomes in six species with diverse genome size, complexity, and all three categories of cGOFs, GAAP outcompetes or achieves comparable results when compared to three other reference-assisted programs, AlignGraph, Ragout and MeDuSa. Conclusions: GAAP uses both cGOF and pair-end reads to create assemblies in genomic scale, and performs better than the currently available reference-assisted assembly tools as it recovers more assemblies and makes fewer false locations, especially for species with extensive rearranged genomes. Our method is a promising solution for reconstruction of genome sequence from short reads of NGS. © 2017 The Author(s).


Wang L.,Peking Union Medical College | Wang L.,Suzhou Institute of Systems Medicine | Wang L.,University of California at Los Angeles | Liu S.-Y.,University of California at Los Angeles | And 29 more authors.
Cell Host and Microbe | Year: 2017

New influenza vaccines that provide effective and broad protection are desperately needed. Live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. However, recent formulations of live attenuated influenza vaccines (LAIVs) have not been protective. We combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate W7-791, a live attenuated mutant virus strain. W7-791 produced only a transient asymptomatic infection in adult and neonatal mice even at doses 100-fold higher than the LD50 of the parent strain. A single administration of W7-791 conferred full protection to mice against lethal challenge with H1N1, H3N2, and H5N1 strains, and improved viral clearance in ferrets. Adoptive transfer of T cells from W7-791-immunized mice conferred heterologous protection, indicating a role for T cell-mediated immunity. These studies present an LAIV development strategy to rapidly generate and screen entire libraries of viral clones. © 2017 Elsevier Inc.


Vacchelli E.,Gustave Roussy Cancer Campus | Vacchelli E.,French Institute of Health and Medical Research | Vacchelli E.,University of Paris Descartes | Vacchelli E.,University Pierre and Marie Curie | And 84 more authors.
Science | Year: 2015

Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer.We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1-/- mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses.


PubMed | CAS Institute of Biophysics, University of Science and Technology of China, Suzhou Institute of Systems Medicine, China Institute of Metrology and 3 more.
Type: Journal Article | Journal: Zhonghua zhong liu za zhi [Chinese journal of oncology] | Year: 2016

The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair (MMR) function on the tumorigenesis of colorectal cancer.The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 (hRad9) gene in these samples were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing. The plasmid of pFLAG-hRad9 (L101M) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9-deleted mouse cells (mRad9(-/-) cells). The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function.Mutation from Leu to Met at the residue 101 (L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9(-/-)+ L101M cells (mRad9-deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.05.6)%, which was significantly lower than that in the mRad9(-/-)+ hRad9 cells [mRad9-deleted mouse cells with ectopic expression of hRad9 gene, (48.07.5)%, P<0.05]. After N-nitroso-N-methylurea (MNU) treatment, the survival rate of mRad9(-/-)+ L101M cells was (33.75.9)%, which was significantly higher than that in the mRad9(-/-)+ hRad9 cells [(21.34.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post-translational modification in mRad9(-/-) cells also led to a reduced MMR activity.Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.


Liu W.,Shanghai JiaoTong University | Liu W.,Suzhou Institute of Systems Medicine | Wu A.,Suzhou Institute of Systems Medicine | Wu A.,Chinese Institute of Basic Medical Sciences
Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015 | Year: 2015

Recent advances in proteomic technologies have enabled high-throughput binary data on protein-protein interactions of E. coli to be released into public domain, and many protein complexes have been identified by experimental methods. Although it has a long study history, a large-scale analysis of protein complex in binary PPI network of E. coli is still absent. We used a novel link clustering algorithm named ELPA to infer protein complexes and functional modules in E. coli PPI network. By mapping our results to 276 gold standard protein complexes and protein function annotations offered by EcoCyc, we found that 80.2% of predicted modules mapping well with one or more complexes, while 92.8% of predicted modules tally well with certain GO terms. Furthermore, we compare our results with MCL algorithm, and evaluated our results with several accuracy measures and biological relevance, the result shows that ELPA achieved an average 18.3% improvement over MCL based on the accuracy measures, which means our method will contributes to uncover the complexes of Ecoli. © 2015 IEEE.


Wang L.,Peking Union Medical College | Wang L.,Suzhou Institute of Systems Medicine | Valderramos S.,University of California at Los Angeles | Wu A.,Peking Union Medical College | And 12 more authors.
Cell Host and Microbe | Year: 2016

Initially isolated in 1947, Zika virus (ZIKV) has recently emerged as a significant public health concern. Sequence analysis of all 41 known ZIKV RNA open reading frames to date indicates that ZIKV has undergone significant changes in both protein and nucleotide sequences during the past half century. Initially isolated in 1947, Zika virus (ZIKV) has recently emerged as a significant public health concern. Sequence analysis of all 41 known ZIKV RNA open reading frames to date indicates that ZIKV has undergone significant changes in both protein and nucleotide sequences during the past half century. © 2016 Elsevier Inc.


Peng Y.,Hunan University | Yang L.,Chinese National Institute for Viral Disease Control and Prevention | Li H.,Hunan University | Zou Y.,Hunan University | And 10 more authors.
Bioinformatics | Year: 2016

Motivation: Timely surveillance of the antigenic dynamics of the influenza virus is critical for accurate selection of vaccine strains, which is important for effective prevention of viral spread and infection. Results: Here, we provide a computational platform, called PREDAC-H3, for antigenic surveillance of human influenza A(H3N2) virus based on the sequence of surface protein hemagglutinin (HA). PREDAC-H3 not only determines the antigenic variants and antigenic cluster (grouped for similar antigenicity) to which the virus belongs, based on HA sequences, but also allows visualization of the spatial distribution and temporal dynamics of antigenic clusters of viruses isolated from around the world, thus assisting in antigenic surveillance of human influenza A(H3N2) virus. © 2016 The Author 2016. Published by Oxford University Press. All rights reserved.


Peng Y.,Hunan University | Wang D.,Chinese National Institute for Viral Disease Control and Prevention | Shu Y.,Chinese National Institute for Viral Disease Control and Prevention | Jiang T.,Peking Union Medical College | Jiang T.,Suzhou Institute of Systems Medicine
Virologica Sinica | Year: 2016

[Figure not available: see fulltext.] © 2016 Wuhan Institute of Virology, CAS and Springer Science+Business Media Singapore


Ci X.,Jilin University | Lv H.,Jilin University | Wang L.,Jilin University | Wang X.,Jilin University | And 9 more authors.
Chemico-Biological Interactions | Year: 2015

Abstract Farrerol, (S)-2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-6,8-dimethyl-4-benzopyrone, isolated from rhododendron, has been shown to have antioxidative potential, but the molecular mechanism underlying this activity remains unclear. The inducible expression of heme oxygenase-1 (HO-1), a potent antioxidative and cytoprotective enzyme, is known to play an important role in cytoprotection in a variety of pathological models. In this study, we evaluated the antioxidative potential of farrerol against oxidative damage and investigated its antioxidative mechanism in RAW 264.7 cells. The molecular mechanism underlying the cytoprotective function of farrerol was determined by analyzing intracellular signaling pathways, transcriptional activation and the inhibitory effect of HO-1 on ROS production. Farrerol induced antioxidant enzymes mRNA expression, HO-1 protein expression and nuclear translocation of NF-E2-related factor 2 in RAW 264.7 macrophage cells. Farrerol down-regulated the expression of the Keap1 protein and the thiol reducing agents attenuated farrerol-induced HO-1 expression. Further investigation utilizing Western blotting and specific inhibitors of Akt, p38, JNK and ERK demonstrated that Akt, p38, and ERK axis of signaling pathway mediates HO-1 expression. Moreover, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was ameliorated by farrerol treatment in a dose-dependent manner, which was abolished by Akt, p38, ERK and HO-1 inhibitors (Snpp). It is hence likely that farrerol inactivated KEAP-1 or activated the Akt, p38 and ERK to facilitate the release of Nrf2 from Keap1 and subsequent reduced the intracellular production of reactive oxygen species via the induction of HO-1 expression. These results support the central role of HO-1 in the cytoprotective effect of farrerol. © 2015 Elsevier Ireland Ltd.


Zhang J.,University of Southern California | Zhu L.,University of Southern California | Lu X.,University of Southern California | Feldman E.R.,University of Florida | And 12 more authors.
PLoS Pathogens | Year: 2015

Human gamma herpesviruses, including Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), are capable of inducing tumors, particularly in in immune-compromised individuals. Due to the stringent host tropism, rodents are resistant to infection by human gamma herpesviruses, creating a significant barrier for the in vivo study of viral genes that contribute to tumorigenesis. The closely-related murine gamma herpesvirus 68 (γHV68) efficiently infects laboratory mouse strains and establishes robust persistent infection without causing apparent disease. Here, we report that a recombinant γHV68 carrying the KSHV G protein-coupled receptor (kGPCR) in place of its murine counterpart induces angiogenic tumors in infected mice. Although viral GPCRs are conserved in all gamma herpesviruses, kGPCR potently activated downstream signaling and induced tumor formation in nude mouse, whereas γHV68 GPCR failed to do so. Recombinant γHV68 carrying kGPCR demonstrated more robust lytic replication ex vivo than wild-type γHV68, although both viruses underwent similar acute and latent infection in vivo. Infection of immunosuppressed mice with γHV68 carrying kGPCR, but not wild-type γHV68, induced tumors in mice that exhibited angiogenic and inflammatory features shared with human Kaposi’s sarcoma. Immunohistochemistry staining identified abundant latently-infected cells and a small number of cells supporting lytic replication in tumor tissue. Thus, mouse infection with a recombinant γHV68 carrying kGPCR provides a useful small animal model for tumorigenesis induced by a human gamma herpesvirus gene in the setting of a natural course of infection. © 2015 Zhang et al.

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