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Article ; Online: Comprehensive analysis of neoantigens derived from structural variation across whole genomes from 2528 tumors.

Shi, Yang / Jing, Biyang / Xi, Ruibin

2023 Volume 24, Issue 1, Page(s) 169

Abstract: Background: Neoantigens are critical for anti-tumor immunity and have been long-envisioned as promising therapeutic targets. However, current neoantigen analyses mostly focus on single nucleotide variations (SNVs) and indel mutations and seldom consider ...

Abstract	Background: Neoantigens are critical for anti-tumor immunity and have been long-envisioned as promising therapeutic targets. However, current neoantigen analyses mostly focus on single nucleotide variations (SNVs) and indel mutations and seldom consider structural variations (SVs) that are also prevalent in cancer. Results: Here, we develop a computational method termed NeoSV, which incorporates SV annotation, protein fragmentation, and MHC binding prediction together, to predict SV-derived neoantigens. Analysis of 2528 whole genomes reveals that SVs significantly contribute to the neoantigen repertoire in both quantity and quality. Whereas most neoantigens are patient-specific, shared neoantigens are identified with high occurrence rates in breast, ovarian, and gastrointestinal cancers. We observe extensive immunoediting on SV-derived neoantigens, especially on clonal events, which suggests their immunogenic potential. We also demonstrate that genomic alteration-related neoantigen burden, which integrates SV-derived neoantigens, depicts the tumor-immune interplay better than tumor neoantigen burden and may improve patient selection for immunotherapy. Conclusions: Our study fills the gap in the current neoantigen repertoire and provides a valuable resource for cancer vaccine development.
MeSH term(s)	Humans ; Antigens, Neoplasm/genetics ; Mutation ; Neoplasms ; Genome ; Genomics ; Immunotherapy/methods
Chemical Substances	Antigens, Neoplasm
Language	English
Publishing date	2023-07-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2040529-7
ISSN	1474-760X ; 1474-760X
ISSN (online)	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-023-03005-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Structural Priors Guided Network for the Corneal Endothelial Cell Segmentation.

Zhang, Yinglin / Xi, Ruiling / Zeng, Lingxi / Towey, Dave / Bai, Ruibin / Higashita, Risa / Liu, Jiang

IEEE transactions on medical imaging

2024 Volume 43, Issue 1, Page(s) 309–320

Abstract: The segmentation of blurred cell boundaries in cornea endothelium microscope images is challenging, which affects the clinical parameter estimation accuracy. Existing deep learning methods only consider pixel-wise classification accuracy and lack of ... ...

Abstract	The segmentation of blurred cell boundaries in cornea endothelium microscope images is challenging, which affects the clinical parameter estimation accuracy. Existing deep learning methods only consider pixel-wise classification accuracy and lack of utilization of cell structure knowledge. Therefore, the segmentation of the blurred cell boundary is discontinuous. This paper proposes a structural prior guided network (SPG-Net) for corneal endothelium cell segmentation. We first employ a hybrid transformer convolution backbone to capture more global context. Then, we use Feature Enhancement (FE) module to improve the representation ability of features and Local Affinity-based Feature Fusion (LAFF) module to propagate structural information among hierarchical features. Finally, we introduce the joint loss based on cross entropy and structure similarity index measure (SSIM) to supervise the training process under pixel and structure levels. We compare the SPG-Net with various state-of-the-art methods on four corneal endothelial datasets. The experiment results suggest that the SPG-Net can alleviate the problem of discontinuous cell boundary segmentation and balance the pixel-wise accuracy and structure preservation. We also evaluate the agreement of parameter estimation between ground truth and the prediction of SPG-Net. The statistical analysis results show a good agreement and correlation.
MeSH term(s)	Endothelium, Corneal/diagnostic imaging ; Entropy ; Epithelial Cells ; Endothelial Cells ; Image Processing, Computer-Assisted
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	622531-7
ISSN	1558-254X ; 0278-0062
ISSN (online)	1558-254X
ISSN	0278-0062
DOI	10.1109/TMI.2023.3300656
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Article ; Online: Identification of eight genes associated with recurrent patellar dislocation.

Xu, Zijie / Huang, Siyuan / Song, Yifan / Xu, Chao / Yan, Hongyu / Linkun, Ouyang / Lv, Bo / Yuan, Fuzhen / Xu, Bingbing / Wang, Haijun / Xi, Ruibin / Yu, Jia-Kuo

iScience

2024 Volume 27, Issue 5, Page(s) 109697

Abstract: The inheritance of recurrent patellar dislocation (RPD) is known, but the susceptible gene remains unidentified. Here, we performed the first whole exome sequencing (WES) cohort study to identify the susceptible genes. The results showed eight genes were ...

Abstract	The inheritance of recurrent patellar dislocation (RPD) is known, but the susceptible gene remains unidentified. Here, we performed the first whole exome sequencing (WES) cohort study to identify the susceptible genes. The results showed eight genes were associated with this disease. Notably, the carboxypeptidase D (CPD) gene showed the highest relevance based on its gene function and tissue expression. Single-cell sequencing results indicate that the CPD gene is involved in the pathophysiological process of RPD through granulocytes. Implicated pathways include nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Wnt/β-catenin signaling, potentially influencing CPD's role in RPD pathogenesis. This study identified the susceptible gene and investigates the potential pathogenesis of RPD, which provided a new prospect for the understanding of RPD. Besides, it would offer the theoretical basis for disease prevention and genetic counseling.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2024.109697
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Article ; Online: Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing.

Cortés-Ciriano, Isidro / Lee, Jake June-Koo / Xi, Ruibin / Jain, Dhawal / Jung, Youngsook L / Yang, Lixing / Gordenin, Dmitry / Klimczak, Leszek J / Zhang, Cheng-Zhong / Pellman, David S / Park, Peter J

Nature genetics

2023 Volume 55, Issue 6, Page(s) 1076

Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-023-01315-z
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: CNV-BAC: Copy number Variation Detection in Bacterial Circular Genome.

Wu, Linjie / Wang, Han / Xia, Yuchao / Xi, Ruibin

Bioinformatics (Oxford, England)

2020 Volume 36, Issue 12, Page(s) 3890–3891

Abstract: Motivation: Whole-genome sequencing (WGS) is widely used for copy number variation (CNV) detection. However, for most bacteria, their circular genome structure and high replication rate make reads more enriched near the replication origin. CNV detection ...

Abstract	Motivation: Whole-genome sequencing (WGS) is widely used for copy number variation (CNV) detection. However, for most bacteria, their circular genome structure and high replication rate make reads more enriched near the replication origin. CNV detection based on read depth could be seriously influenced by such replication bias. Results: We show that the replication bias is widespread using ∼200 bacterial WGS data. We develop CNV-BAC (CNV-Bacteria) that can properly normalize the replication bias and other known biases in bacterial WGS data and can accurately detect CNVs. Simulation and real data analysis show that CNV-BAC achieves the best performance in CNV detection compared with available algorithms. Availability and implementation: CNV-BAC is available at https://github.com/XiDsLab/CNV-BAC. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Algorithms ; Computer Simulation ; DNA Copy Number Variations ; Genome, Bacterial/genetics ; High-Throughput Nucleotide Sequencing ; Whole Genome Sequencing
Language	English
Publishing date	2020-03-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btaa208
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Zs.A 2374: Show issues

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Book ; Online: Single-cell gene regulatory network analysis for mixed cell populations with applications to COVID-19 single cell data

Tang, Junjie / Wang, Changhu / Xiao, Feiyi / Xi, Ruibin

2022

Abstract: Gene regulatory network (GRN) refers to the complex network formed by regulatory interactions between genes in living cells. In this paper, we consider inferring GRNs in single cells based on single cell RNA sequencing (scRNA-seq) data. In scRNA-seq, ... ...

Abstract	Gene regulatory network (GRN) refers to the complex network formed by regulatory interactions between genes in living cells. In this paper, we consider inferring GRNs in single cells based on single cell RNA sequencing (scRNA-seq) data. In scRNA-seq, single cells are often profiled from mixed populations and their cell identities are unknown. A common practice for single cell GRN analysis is to first cluster the cells and infer GRNs for every cluster separately. However, this two-step procedure ignores uncertainty in the clustering step and thus could lead to inaccurate estimation of the networks. To address this problem, we propose to model scRNA-seq by the mixture multivariate Poisson log-normal (MPLN) distribution. The precision matrices of the MPLN are the GRNs of different cell types and can be jointly estimated by maximizing MPLN's lasso-penalized log-likelihood. We show that the MPLN model is identifiable and the resulting penalized log-likelihood estimator is consistent. To avoid the intractable optimization of the MPLN's log-likelihood, we develop an algorithm called VMPLN based on the variational inference method. Comprehensive simulation and real scRNA-seq data analyses reveal that VMPLN performs better than the state-of-the-art single cell GRN methods. Comment: 95 pages,28 figures
Keywords	Quantitative Biology - Molecular Networks ; Statistics - Methodology
Subject code	310
Publishing date	2022-05-23
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The shaping of cancer genomes with the regional impact of mutation processes.

Lee, Soo-Youn / Wang, Han / Cho, Hae Jin / Xi, Ruibin / Kim, Tae-Min

Experimental & molecular medicine

2022 Volume 54, Issue 7, Page(s) 1049–1060

Abstract: Mutation signature analysis has been used to infer the contributions of various DNA mutagenic-repair events in individual cancer genomes. Here, we build a statistical framework using a multinomial distribution to assign individual mutations to their ... ...

Abstract	Mutation signature analysis has been used to infer the contributions of various DNA mutagenic-repair events in individual cancer genomes. Here, we build a statistical framework using a multinomial distribution to assign individual mutations to their cognate mutation signatures. We applied it to 47 million somatic mutations in 1925 publicly available cancer genomes to obtain a mutation signature map at the resolution of individual somatic mutations. Based on mutation signature-level genetic-epigenetic correlative analyses, mutations with transcriptional and replicative strand asymmetries show different enrichment patterns across genomes, and "transcribed" chromatin states and gene boundaries are particularly vulnerable to transcription-coupled repair activities. While causative processes of cancer-driving mutations can be diverse, as shown for converging effects of multiple mutational processes on TP53 mutations, the substantial fraction of recurrently mutated amino acids points to specific mutational processes, e.g., age-related C-to-T transition for KRAS p.G12 mutations. Our investigation of evolutionary trajectories with respect to mutation signatures further revealed that candidate pairs of early- vs. late-operative mutation processes in cancer genomes represent evolutionary dynamics of multiple mutational processes in the shaping of cancer genomes. We also observed that the local mutation clusters of kataegis often include mutations arising from multiple mutational processes, suggestive of a locally synchronous impact of multiple mutational processes on cancer genomes. Taken together, our examination of the genome-wide landscape of mutation signatures at the resolution of individual somatic mutations shows the spatially and temporally distinct mutagenesis-repair-replication histories of various mutational processes and their effects on shaping cancer genomes.
MeSH term(s)	DNA Repair ; Genome, Human ; Humans ; Mutagenesis ; Mutation ; Neoplasms/genetics
Language	English
Publishing date	2022-07-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1328915-9
ISSN	2092-6413 ; 1226-3613 ; 0378-8512
ISSN (online)	2092-6413
ISSN	1226-3613 ; 0378-8512
DOI	10.1038/s12276-022-00808-x
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Zs.A 4775: Show issues

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Article ; Online: Single-cell gene fusion detection by scFusion

Zijie Jin / Wenjian Huang / Ning Shen / Juan Li / Xiaochen Wang / Jiqiao Dong / Peter J. Park / Ruibin Xi

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 12

Abstract: Gene fusions are an important class of mutations in tumor genomes. Here, the authors develop a single-cell gene fusion detection method scFusion and demonstrate its applications in cancer single-cell studies. ...

Abstract	Gene fusions are an important class of mutations in tumor genomes. Here, the authors develop a single-cell gene fusion detection method scFusion and demonstrate its applications in cancer single-cell studies.
Keywords	Science ; Q
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nano-microflora Interaction Inducing Pulmonary Inflammation by Pyroptosis.

Gao, Meng / Chen, Jie / Chen, Changzhi / Xie, Maomao / Xie, Qianqian / Li, Wenjie / Jiang, Jie / Liu, Xi / Cai, Xiaoming / Zheng, Huizhen / Zhang, Chengdong / Li, Ruibin

Environmental science & technology

2024

Abstract: Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of ... ...

Abstract	Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.
Language	English
Publishing date	2024-04-27
Publishing country	United States
Document type	Journal Article
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.4c00141
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Article ; Online: Doped Graphene To Mimic the Bacterial NADH Oxidase for One-Step NAD

Liu, Xi / Li, Jingkun / Zitolo, Andrea / Gao, Meng / Jiang, Jun / Geng, Xiangtian / Xie, Qianqian / Wu, Di / Zheng, Huizhen / Cai, Xiaoming / Lu, Jianmei / Jaouen, Frédéric / Li, Ruibin

Journal of the American Chemical Society

2023 Volume 145, Issue 5, Page(s) 3108–3120

Abstract: Nicotinamide adenine dinucleotide (NAD) is a critical regulator of metabolic networks, and declining levels of its oxidized form, ... ...

Abstract	Nicotinamide adenine dinucleotide (NAD) is a critical regulator of metabolic networks, and declining levels of its oxidized form, NAD
MeSH term(s)	Mice ; Animals ; NAD/metabolism ; Graphite ; Oxidation-Reduction ; Mammals/metabolism ; Bacteria/metabolism ; Dietary Supplements
Chemical Substances	NADH oxidase (EC 1.6.-) ; NAD (0U46U6E8UK) ; Graphite (7782-42-5)
Language	English
Publishing date	2023-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/jacs.2c12336
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