We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were ...more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.
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•We build the genomic and transcriptomic landscape of 465 primary TNBCs•Chinese TNBC cases demonstrate more PIK3CA mutations and LAR subtype•Transcriptomic data classify TNBCs into four subtypes•Multi-omics profiling identifies potential targets within specific TNBC subtypes
Jiang et al. characterize primary Chinese triple-negative breast cancer (TNBC) and classify it into four subtypes. They find that these TNBCs have more frequent PIK3CA mutations and chromosome 22q11 copy-number gains than non-Asian TNBCs and that the LAR subtype has more ERBB2 somatic mutations and CDKN2A loss.
Due to the tolerance of mismatches between gRNA and targeting sequence, base editors frequently induce unwanted Cas9-dependent off-target mutations. Here, to develop models to predict such ...off-targets, we design gRNA-off- target pairs for adenine base editors (ABEs) and cytosine base editors (CBEs) and stably integrate them into the human cells. After five days of editing, we obtain valid efficiency datasets of 54,663 and 55,727 off-targets for ABEs and CBEs, respectively. We use the datasets to train deep learning models, resulting in ABEdeepoff and CBEdeepoff, which can predict off-target sites. We use these tools to predict off-targets for a panel of endogenous loci and achieve Spearman correlation values varying from 0.710 to 0.859. Finally, we develop an integrated tool that is freely accessible via an online web server http://www.deephf.com/#/bedeep/bedeepoff . These tools could facilitate minimizing the off-target effects of base editing.
Polo-like kinase 1 (PLK1) is a potential prognostic marker in colorectal cancer (CRC). Nevertheless, the clinicopathological and prognostic roles of PLK1 in CRC are still undefined. Therefore, we ...performed a meta-analysis to investigate the clinicopathological and prognostic relevance of PLK1 expression in CRC patients.
Studies published between 2003 and 2016 were selected for the meta-analysis based on an electronic literature search (PubMed, EMBASE and Chinese databases). Studies that investigated the clinicopathological and prognostic impacts of PLK1 expression in CRC patients were included for this analysis.
Eleven studies that enrolled 1147 CRC patients were included in our meta-analysis. The effect of PLK1 level on overall survival (OS) was reported in five studies, which included 702 patients. Ten studies investigated the clinicopathological role of PLK1 expression in CRC patients. Consequently, PLK1 overexpression was associated with poorer OS in CRC patients. Furthermore, the results revealed that higher PLK1 levels were also observed in CRC tissues compared with that of normal colorectal tissues. In addition, this meta-analysis also revealed positive correlations between PLK1 upregulation and lymph node metastasis or invasion. PLK1 overexpression was significantly correlated with advanced TNM stages and higher Dukes stages.
This meta-analysis strongly supports the hypothesis that PLK1 might serve as an important factor in evaluating the biological behavior and prognosis of CRC.
•Eleven studies enrolling 1147 CRC patients were included for our meta-analysis.•PLK1 overexpression was associated with poorer OS in CRC patients.•The results revealed that higher PLK1 level was also observed in CRC tissues compared with normal colorectal tissues.•This meta-analyses also revealed the positive correlations between PLK1 up-regulation and lymph node metastasis or invasion.•The PLK1 overexpression was significantly correlated with advanced TNM stages and higher Dukes stages.
Abstract
The Quartet Data Portal facilitates community access to well-characterized reference materials, reference datasets, and related resources established based on a family of four individuals ...with identical twins from the Quartet Project. Users can request DNA, RNA, protein, and metabolite reference materials, as well as datasets generated across omics, platforms, labs, protocols, and batches. Reproducible analysis tools allow for objective performance assessment of user-submitted data, while interactive visualization tools support rapid exploration of reference datasets. A closed-loop “distribution-collection-evaluation-integration” workflow enables updates and integration of community-contributed multiomics data. Ultimately, this portal helps promote the advancement of reference datasets and multiomics quality control.
Bound state in the continuum (BIC), as a novel eigenmode with infinitely high-quality factor, has received great attention in modern optical science. Mode coupling in dielectric metasurfaces opens ...possibilities in searching for robust BICs. Here, we discover multiple BICs in periodic dielectric resonators composed of a silicon rectangular bar and a silicon ring in one lattice. For the symmetry-protected BIC at-Γ point, a sharp electromagnetically induced transparency window can be formed by either tilting incident angle to induce the 'bright-bright' mode coupling, or by displacing the ring to generate the 'bright-dark' mode coupling. Besides, the coupling between two resonators leads to a new energy band in the dielectric metasurface. As a result, two off-Γ BICs are formed owing to avoided crossings with two energy bands, and another one belongs to the single-resonance parametric BIC. Thus, our coupled resonators possess superior abilities to judiciously engineer BICs via versatile physical mechanisms. Taking advantage exclusively of coupled resonators in dielectric metasurfaces provides fresh insights into the creation of both symmetry-protected and accidental BICs, which enables profound advancements in designing novel photonic devices.
Abstract
Background
Batch effects are notoriously common technical variations in multiomics data and may result in misleading outcomes if uncorrected or over-corrected. A plethora of batch-effect ...correction algorithms are proposed to facilitate data integration. However, their respective advantages and limitations are not adequately assessed in terms of omics types, the performance metrics, and the application scenarios.
Results
As part of the Quartet Project for quality control and data integration of multiomics profiling, we comprehensively assess the performance of seven batch effect correction algorithms based on different performance metrics of clinical relevance, i.e., the accuracy of identifying differentially expressed features, the robustness of predictive models, and the ability of accurately clustering cross-batch samples into their own donors. The ratio-based method, i.e., by scaling absolute feature values of study samples relative to those of concurrently profiled reference material(s), is found to be much more effective and broadly applicable than others, especially when batch effects are completely confounded with biological factors of study interests. We further provide practical guidelines for implementing the ratio based approach in increasingly large-scale multiomics studies.
Conclusions
Multiomics measurements are prone to batch effects, which can be effectively corrected using ratio-based scaling of the multiomics data. Our study lays the foundation for eliminating batch effects at a ratio scale.
Abstract
One important aspect of precision medicine aims to deliver the right medicine to the right patient at the right dose at the right time based on the unique ‘omics’ features of each individual ...patient, thus maximizing drug efficacy and minimizing adverse drug reactions. However, fragmentation and heterogeneity of available data makes it challenging to readily obtain first-hand information regarding some particular diseases, drugs, genes and variants of interest. Therefore, we developed the Precision Medicine Knowledgebase (PreMedKB) by seamlessly integrating the four fundamental components of precision medicine: diseases, genes, variants and drugs. PreMedKB allows for search of comprehensive information within each of the four components, the relationships between any two or more components, and importantly, the interpretation of the clinical meanings of a patient's genetic variants. PreMedKB is an efficient and user-friendly tool to assist researchers, clinicians or patients in interpreting a patient's genetic profile in terms of discovering potential pathogenic variants, recommending therapeutic regimens, designing panels for genetic testing kits, and matching patients for clinical trials. PreMedKB is freely accessible and available at http://www.fudan-pgx.org/premedkb/index.html#/home.
Esophageal cancer (EC) is considered as one of the deadliest malignancies with respect to incidence and mortality rate, and numerous risk factors may affect the prognosis of EC patients. For better ...understanding of the risk factors associated with the onset and prognosis of this malignancy, we develop an interactive web-based tool for the convenient analysis of clinical and survival characteristics of EC patients.
The clinical data were obtained from The Surveillance, Epidemiology, and End Results (SEER) database. Seven analysis and visualization modules were built with Shiny.
The Esophageal Cancer Clinical Data Interactive Analysis (ECCDIA, http://webapps.3steps.cn/ECCDIA/ ) was developed to provide basic data analysis, visualization, survival analysis, and nomogram of the overall group and subgroups of 77,273 EC patients recorded in SEER. The basic data analysis modules contained distribution analysis of clinical factor ratios, Sankey plot analysis for relationships between clinical factors, and a map for visualizing the distribution of clinical factors. The survival analysis included Kaplan-Meier (K-M) analysis and Cox analysis for different subgroups of EC patients. The nomogram module enabled clinicians to precisely predict the survival probability of different subgroups of EC patients.
ECCDIA provides clinicians with an interactive prediction and visualization tool for visualizing invaluable clinical and prognostic information of individual EC patients, further providing useful information for better understanding of esophageal cancer.
Various laboratory-developed metabolomic methods lead to big challenges in inter-laboratory comparability and effective integration of diverse datasets.
As part of the Quartet Project, we establish a ...publicly available suite of four metabolite reference materials derived from B lymphoblastoid cell lines from a family of parents and monozygotic twin daughters. We generate comprehensive LC-MS-based metabolomic data from the Quartet reference materials using targeted and untargeted strategies in different laboratories. The Quartet multi-sample-based signal-to-noise ratio enables objective assessment of the reliability of intra-batch and cross-batch metabolomics profiling in detecting intrinsic biological differences among the four groups of samples. Significant variations in the reliability of the metabolomics profiling are identified across laboratories. Importantly, ratio-based metabolomics profiling, by scaling the absolute values of a study sample relative to those of a common reference sample, enables cross-laboratory quantitative data integration. Thus, we construct the ratio-based high-confidence reference datasets between two reference samples, providing "ground truth" for inter-laboratory accuracy assessment, which enables objective evaluation of quantitative metabolomics profiling using various instruments and protocols.
Our study provides the community with rich resources and best practices for inter-laboratory proficiency tests and data integration, ensuring reliability of large-scale and longitudinal metabolomic studies.
MicroRNA (miRNA) played an important role in the progression of liver cancer and its diagnostic and prognostic values have been frequently studied. However, different microarray techniques and small ...sample size led to inconsistent findings in previous studies. We performed a comprehensive meta-analysis of a total of 357 tumor and 283 noncancerous samples from 12 published miRNA expression studies using robust rank aggregation method. As a result, we identified a statistically significant meta-signature of five upregulated (miR-221, miR-222, miR-93, miR-21 and miR-224) and four downregulated (miR-130a, miR-195, miR-199a and miR-375) miRNAs. We then conducted miRNA target prediction and pathway enrichment analysis to find what biological process these miRNAs might affect. We found that most of the pathways were frequently associated with cell signaling and cancer pathogenesis. Thus these miRNAs may involve in the onset and progression of liver cancer and serve as potential diagnostic and therapeutic targets of this malignancy.
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