Publications by authors named "Qiushi Zhang"

43 Publications

Outcomes of reproduction following cesarean scar pregnancy treatment: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2021 May 10;262:80-92. Epub 2021 May 10.

Department of Gynecology, Guangdong Second Provincial General Hospital, Guangzhou, China.

Objectives: To explore the reproductive outcomes of women with a history of cesarean scar pregnancy (CSP) and the influence of various treatments on subsequent pregnancy outcomes.

Study Design: The PubMed, Embase, Medline, Cochrane Library and ClinicalTrial.gov databases were searched for studies with the outcomes of pregnancy after CSP treatment. Studies that reported reproductive outcomes after CSP with more than 5 followed cases were included. The main data collected includes the treatment methods of CSP and subsequent pregnancy outcomes. The main information includes intrauterine pregnancy, recurrent CSP (RCSP), and spontaneous miscarriage, while the secondary information includes complications during pregnancies and the outcomes of childbirths. According to different treatments (conservative treatment, surgical treatment without resection of cesarean scar, and surgical treatment with resection of cesarean scar), a stratified analysis was carried out to compare the influence of treatments on subsequent pregnancy outcomes.

Results: A total of 32 studies including 3380 cases of CSP met the inclusion criteria, of which 583 cases conceived again after treatment (including 292 cases of unexpected pregnancy), and finally 178 cases delivered successfully. The follow-up time ranged from 3 to 72 months. Among women with fertility requirements, a total of 291 cases in 403 women were successfully conceived during the follow-up period in 15 studies. Thence the pregnancy rate of women with fertility requirements was 76.2 %. Among all of the 583 successfully conceived women, 83.4 % of them had intrauterine pregnancy, while 15.3 % of cases were RCSP. The total ectopic pregnancy rate reached 16.6 %, covering RCSP and other sites of ectopic pregnancy. 14.6 % of intrauterine pregnancy experienced spontaneous miscarriage. The intrauterine pregnancy rates of the conservative treatment group, the surgical treatment without resection of cesarean scar group, and the surgical treatment with resection of cesarean scar group were 93.1 %, 80.1 % and 86.0 % respectively; the corresponding RCSP rates were 6.9 %, 15.6 % and 14.0 % respectively; and the corresponding spontaneous miscarriage rates were 20.7 %, 13.9 % and 22.2 % respectively.

Conclusion: The outcomes of reproduction after CSP included intrauterine pregnancy, RCSP and other sites of ectopic pregnancy. Women with a history of CSP still have a high pregnancy rate, but the risk of RCSP and spontaneous miscarriage is also increased. It is impossible to clarify the effect of different treatments on subsequent pregnancy. Whether the resection and repair of cesarean scar can ameliorate reproductive outcomes needs to be further assessed. Further large-scale prospective studies, even RCTs with long-term follow-up are needed to expound the outcomes of reproduction after CSP and the effect of different treatments on subsequent reproductive outcomes.
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http://dx.doi.org/10.1016/j.ejogrb.2021.05.010DOI Listing
May 2021

Optically Driven Gold Nanoparticles Seed Surface Bubble Nucleation in Plasmonic Suspension.

Nano Lett 2021 May 3. Epub 2021 May 3.

Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States.

Photothermal surface bubbles play important roles in applications like microfluidics and biosensing, but their formation on transparent substrates immersed in a plasmonic nanoparticle (NP) suspension has an unknown origin. Here, we reveal NPs deposited on the transparent substrate by optical forces are responsible for the nucleation of such photothermal surface bubbles. We show the surface bubble formation is always preceded by the optically driven NPs moving toward and deposited to the surface. Interestingly, such optically driven motion can happen both along and against the photon stream. The laser power density thresholds to form a surface bubble drastically differ depending on if the surface is forward- or backward-facing the light propagation direction. We attributed this to different optical power densities needed to enable optical pulling and pushing of NPs in the suspension, as optical pulling requires higher light intensity to excite supercavitation around NPs to enable proper optical configuration.
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http://dx.doi.org/10.1021/acs.nanolett.0c04913DOI Listing
May 2021

Investigation of edge states in artificial graphene nano-flakes.

J Phys Condens Matter 2021 May 5;33(22). Epub 2021 May 5.

Department of Physics, The Hong Kong University of Science and Technology, Hong Kong, People's Republic of China.

Graphene nano-flakes (GNFs) are predicted to host spin-polarized metallic edge states, which are envisioned for exploration of spintronics at the nanometer scale. To date, experimental realization of GNFs is only in its infancy because of the limitation of precise cutting or synthesizing methods at the nanometer scale. Here, we use low temperature scanning tunneling microscope to manipulate coronene molecules on a Cu(111) surface to build artificial triangular and hexagonal GNFs with either zigzag or armchair type of edges. We observe that an electronic state at the Dirac point emerges only in the GNFs with zigzag edges and localizes at the outmost lattice sites. The experimental results agree well with the tight-binding calculations. Our work renders an experimental confirmation of the predicated edge states of the GNFs.
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http://dx.doi.org/10.1088/1361-648X/abe819DOI Listing
May 2021

Multi-organ proteomic landscape of COVID-19 autopsies.

Cell 2021 02 9;184(3):775-791.e14. Epub 2021 Jan 9.

Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.
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http://dx.doi.org/10.1016/j.cell.2021.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794601PMC
February 2021

ProteomeExpert: a docker image based web-server for exploring, modeling, visualizing, and mining quantitative proteomic data sets.

Bioinformatics 2021 Jan 8. Epub 2021 Jan 8.

Zhejiang Provincial Laboratory of Life Sciences and Biomedicine, Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, Zhejiang, China Province.

: The rapid progresses of high throughput sequencing technology-based omics and mass spectrometry (MS)-based proteomics such as data-independent acquisition (DIA) and its penetration to clinical studies have generated increasing number of proteomic data sets containing 100 s-1000s samples. To analyze these quantitative proteomic data sets and other -omics data sets more efficiently and conveniently, we present a web server-based software tool ProteomeExpert implemented in Docker, which offers various analysis tools for experimental design, data mining, interpretation, and visualization of quantitative proteomic data sets. ProteomeExpert can be deployed on an operating system with Docker installed or with R language environment.

Availability And Implementation: The Docker image of ProteomeExpert is freely available from https://hub.docker.com/r/lifeinfo/proteomeexpert. The source code of ProteomeExpert is also openly accessible at http://www.github.com/lifeinfo/ProteomeExpert/. In addition, a demo server is provided at https://proteomic.shinyapps.io/peserver/.

Supplementary Information: SUPPLEMENTARY DATA ARE AVAILABLE AT BIOINFORMATICS ONLINE.
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http://dx.doi.org/10.1093/bioinformatics/btaa1088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055226PMC
January 2021

Multivariate genome wide association and network analysis of subcortical imaging phenotypes in Alzheimer's disease.

BMC Genomics 2020 Dec 29;21(Suppl 11):896. Epub 2020 Dec 29.

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Background: Genome-wide association studies (GWAS) have identified many individual genes associated with brain imaging quantitative traits (QTs) in Alzheimer's disease (AD). However single marker level association discovery may not be able to address the underlying biological interactions with disease mechanism.

Results: In this paper, we used the MGAS (Multivariate Gene-based Association test by extended Simes procedure) tool to perform multivariate GWAS on eight AD-relevant subcortical imaging measures. We conducted multiple iPINBPA (integrative Protein-Interaction-Network-Based Pathway Analysis) network analyses on MGAS findings using protein-protein interaction (PPI) data, and identified five Consensus Modules (CMs) from the PPI network. Functional annotation and network analysis were performed on the identified CMs. The MGAS yielded significant hits within APOE, TOMM40 and APOC1 genes, which were known AD risk factors, as well as a few new genes such as LAMA1, XYLB, HSD17B7P2, and NPEPL1. The identified five CMs were enriched by biological processes related to disorders such as Alzheimer's disease, Legionellosis, Pertussis, and Serotonergic synapse.

Conclusions: The statistical power of coupling MGAS with iPINBPA was higher than traditional GWAS method, and yielded new findings that were missed by GWAS. This study provides novel insights into the molecular mechanism of Alzheimer's Disease and will be of value to novel gene discovery and functional genomic studies.
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http://dx.doi.org/10.1186/s12864-020-07282-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771059PMC
December 2020

Convergent network effects along the axis of gene expression during prostate cancer progression.

Genome Biol 2020 12 14;21(1):302. Epub 2020 Dec 14.

CECAD, University of Cologne, Cologne, Germany.

Background: Tumor-specific genomic aberrations are routinely determined by high-throughput genomic measurements. It remains unclear how complex genome alterations affect molecular networks through changing protein levels and consequently biochemical states of tumor tissues.

Results: Here, we investigate the propagation of genomic effects along the axis of gene expression during prostate cancer progression. We quantify genomic, transcriptomic, and proteomic alterations based on 105 prostate samples, consisting of benign prostatic hyperplasia regions and malignant tumors, from 39 prostate cancer patients. Our analysis reveals the convergent effects of distinct copy number alterations impacting on common downstream proteins, which are important for establishing the tumor phenotype. We devise a network-based approach that integrates perturbations across different molecular layers, which identifies a sub-network consisting of nine genes whose joint activity positively correlates with increasingly aggressive tumor phenotypes and is predictive of recurrence-free survival. Further, our data reveal a wide spectrum of intra-patient network effects, ranging from similar to very distinct alterations on different molecular layers.

Conclusions: This study uncovers molecular networks with considerable convergent alterations across tumor sites and patients. It also exposes a diversity of network effects: we could not identify a single sub-network that is perturbed in all high-grade tumor regions.
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http://dx.doi.org/10.1186/s13059-020-02188-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737297PMC
December 2020

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery.

Genomics Proteomics Bioinformatics 2020 04 12;18(2):104-119. Epub 2020 Aug 12.

Department of Anatomical Pathology, Singapore General Hospital, Singapore 169608, Singapore.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
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http://dx.doi.org/10.1016/j.gpb.2019.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646093PMC
April 2020

The factors influencing sludge incineration residue (SIR)-based magnesium potassium phosphate cement and the solidification/stabilization characteristics and mechanisms of heavy metals.

Chemosphere 2020 Dec 26;261:127789. Epub 2020 Jul 26.

Shenzhen Engineering Laboratory of Aerospace Detection and Imaging, Department of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen), Shenzhen, 518055, China.

Magnesium potassium phosphate cement (MKPC) is prepared from MgO and KHPO through an acid-base reaction and has been widely used in the rapid repairs of building structures and the solidification/stabilization (S/S) of heavy metals (HMs). The use of sludge incineration residue (SIR) rich in phosphorus resources to prepare SIR-based MKPC can achieve the reclamation of SIR and efficient HM S/S. Herein, based on the exploration of the optimal MKPC magnesia/phosphate ratio (M/P), the effects of SIR and HMs on the performance of the matrix and its interaction mechanism were comprehensively investigated. The results indicated that the compressive strength of the SIR-based MKPC increased first and then decreased with the gradual increase of SIR incorporation; the optimal was reached at 40.31 MPa when the SIR incorporation was 5 wt%. The peak signal and crystal lattice of Pb(PO) indicated that there is a mixed effect between HMs (in SIR) and KHPO. The Visual MINTEQ analysis results also indicated that HMs are precipitated as HM phosphates. The formation of HM phosphates not only increases the M/P (with 30 wt% SIR, M/P increased by 0.019), affecting the microstructure and changing the compressive strength of the matrix, but also promotes the transformation of HMs from the bioavailable to the more stable residual forms. The residual forms of the six HMs were all above 84% after S/S. Therefore, the SIR-based MKPC preparation significantly immobilized the HMs; particularly, the leaching toxicities of Cu (96.6%) and Zn (96.3%) were alleviated.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127789DOI Listing
December 2020

Surface Bubble Growth in Plasmonic Nanoparticle Suspension.

ACS Appl Mater Interfaces 2020 Jun 27;12(23):26680-26687. Epub 2020 May 27.

Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States.

Understanding the growth dynamics of the microbubbles produced by plasmonic heating can benefit a wide range of applications like microfluidics, catalysis, micropatterning, and photothermal energy conversion. Usually, surface plasmonic bubbles are generated on plasmonic structures predeposited on the surface subject to laser heating. In this work, we investigate the growth dynamics of surface microbubbles generated in plasmonic nanoparticle (NP) suspension. We observe much faster bubble growth rates compared to those in pure water with surface plasmonic structures. Our analyses show that the volumetric heating effect around the surface bubble due to the existence of NPs in the suspension is the key to explaining this difference. Such volumetric heating increases the temperature around the surface bubble more efficiently compared to surface heating which enhances the expelling of dissolved gas. We also find that the bubble growth rates can be tuned in a very wide range by changing the concentration of NPs, besides laser power and dissolved gas concentration.
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http://dx.doi.org/10.1021/acsami.0c05448DOI Listing
June 2020

A circulating extracellular vesicles-based novel screening tool for colorectal cancer revealed by shotgun and data-independent acquisition mass spectrometry.

J Extracell Vesicles 2020 14;9(1):1750202. Epub 2020 Apr 14.

Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

: Early screening for colorectal cancer (CRC) is essential to improve its prognosis. Liquid biopsies are increasingly being considered for diagnosing cancer due to low invasiveness and high reproducibility. In addition, circulating extracellular vesicles (crEVs, extracellular vesicles isolated from plasma) expressing tumour-specific proteins are potential biomarkers for various cancers. Here, we present a data-independent acquisition (DIA)-mass spectrometry (MS)-based diagnostic method for liquid biopsies. : Extracellular vesicles (EVs) were isolated from culture supernatants of human CRC cell lines, and plasma of patients with CRC at different tumour stages, by overnight ultracentrifugation coupled with sucrose density gradient centrifugation. Tumour-specific EV proteins were prioritized using Tandem Mass Tag (TMT)-based shotgun proteomics and phosphoproteomics. The results were verified in a second independent cohort and a mouse tumour-bearing model using Western blotting (WB). The candidate biomarkers were further validated in a third cohort by DIA-MS. Finally, the DIA-MS methodology was accelerated to permit high-throughput detection of EV biomarkers in another independent cohort of patients with CRC and healthy controls. : High levels of total and phosphorylated fibronectin 1 (FN1) in crEVs, haptoglobin (HP), S100A9 and fibrinogen α chain (FGA) were significantly associated with cancer progression. FGA was the most dominant biomarker candidate. Analysis of the human CRC cell lines and the mouse model indicated that FGA+ crEVs were likely released by CRC cells. Furthermore, fast DIA-MS and parallel reaction monitoring (PRM)-MS both confirmed that FGA+ crEVs could distinguish colon adenoma with an area of curve (AUC) in the receiver operating characteristic (ROC) curve of 0.949 and patients with CRC (AUC of ROC is 1.000) from healthy individuals. The performance outperformed conventional tumour biomarkers. The DIA-MS quantification of FGA+ crEVs among three groups agreed with that from PRM-MS. : DIA-MS detection of FGA+ crEVs is a potential rapid and non-invasive screening tool to identify early stage CRC. FGA: fibrinogen α chain; CRC: colorectal cancer; crEVs: circulating extracellular vesicles; EV: extracellular vesicles;MS: mass spectrometry; WB: Western blotting; ROC: receiver operating characteristic; PRM: Parallel Reaction Monitoring; GPC1: Glypican-1; GO: Gene ontology; TEM: transmission electron microscopy; FN1: Fibronectin 1; HP: haptoglobin; TMT: Tandem Mass Tag; LC-MS/MS: liquid chromatography coupled to tandem mass spectrometry; DIA: data-independent acquisition; DDA: data-dependent acquisition; CiRT: Common internal Retention Time standards;AGC: Automatic gain control; AUC: area under curve.
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http://dx.doi.org/10.1080/20013078.2020.1750202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178829PMC
April 2020

Accelerated Lysis and Proteolytic Digestion of Biopsy-Level Fresh-Frozen and FFPE Tissue Samples Using Pressure Cycling Technology.

J Proteome Res 2020 05 30;19(5):1982-1990. Epub 2020 Mar 30.

Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, China.

Pressure cycling technology (PCT)-assisted tissue lysis and digestion have facilitated reproducible and high-throughput proteomic studies of both fresh-frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tissue of biopsy scale for biomarker discovery. Here, we present an improved PCT method accelerating the conventional procedures by about two-fold without sacrificing peptide yield, digestion efficiency, peptide, and protein identification. The time required for processing 16 tissue samples from tissues to peptides is reduced from about 6 to about 3 h. We analyzed peptides prepared from FFPE hepatocellular carcinoma (HCC) tissue samples by the accelerated PCT method using multiple MS acquisition methods, including short-gradient SWATH-MS, PulseDIA-MS, and 10-plex TMT-based shotgun MS. The data showed that up to 8541 protein groups could be reliably quantified from the thus prepared peptide samples. We applied the accelerated sample preparation method to 25 pairs (tumorous and matched benign) of HCC samples followed by a single-shot, 15 min gradient SWATH-MS analysis. An average of 18 453 peptides from 2822 proteins were quantified in at least 20% samples in this cohort, while 1817 proteins were quantified in at least 50% samples. The data not only identified the previously known dysregulated proteins such as MCM7, MAPRE1, and SSRP1 but also discovered promising novel protein markers, including DRAP1 and PRMT5. In summary, we present an accelerated PCT protocol that effectively doubles the throughput of PCT-assisted sample preparation of biopsy-level FF and FFPE samples without compromising protein digestion efficiency, peptide yield, and protein identification.
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http://dx.doi.org/10.1021/acs.jproteome.9b00790DOI Listing
May 2020

Accelerated Protein Biomarker Discovery from FFPE Tissue Samples Using Single-Shot, Short Gradient Microflow SWATH MS.

J Proteome Res 2020 07 13;19(7):2732-2741. Epub 2020 Feb 13.

Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, 18 Shilongshan Road, Hangzhou, Zhejiang 310024, China.

We reported and evaluated a microflow, single-shot, short gradient SWATH MS method intended to accelerate the discovery and verification of protein biomarkers in preclassified clinical specimens. The method uses a 15 min gradient microflow-LC peptide separation, an optimized SWATH MS window configuration, and OpenSWATH software for data analysis. We applied the method to a cohort containing 204 FFPE tissue samples from 58 prostate cancer patients and 10 benign prostatic hyperplasia patients. Altogether we identified 27,975 proteotypic peptides and 4037 SwissProt proteins from these 204 samples. Compared to a reference SWATH method with a 2 h gradient, we found 3800 proteins were quantified by the two methods on two different instruments with relatively high consistency ( = 0.77). The accelerated method consumed only 17% instrument time, while quantifying 80% of proteins compared to the 2 h gradient SWATH. Although the missing value rate increased by 20%, batch effects reduced by 21%. 75 deregulated proteins measured by the accelerated method were selected for further validation. A shortlist of 134 selected peptide precursors from the 75 proteins were analyzed using MRM-HR, and the results exhibited high quantitative consistency with the 15 min SWATH method ( = 0.89) in the same sample set. We further verified the applicability of these 75 proteins in separating benign and malignant tissues (AUC = 0.99) in an independent prostate cancer cohort ( = 154). Altogether, the results showed that the 15 min gradient microflow SWATH accelerated large-scale data acquisition by 6 times, reduced batch effect by 21%, introduced 20% more missing values, and exhibited comparable ability to separate disease groups.
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http://dx.doi.org/10.1021/acs.jproteome.9b00671DOI Listing
July 2020

Awareness and Attitudes Toward Advance Care Planning Among Community-Dwelling Older Adults in China: A Mixed-Methods Study.

Am J Hosp Palliat Care 2020 Sep 13;37(9):743-749. Epub 2020 Feb 13.

School of Nursing and Health, Zhengzhou University, Zhengzhou, China.

Context: Quality of palliative care and death in mainland China is at a low level of the rest of the world, the public is lacked of proper understanding of the relevant information is one of the important reasons. There has been a shift in policy of palliative care in municipalities recently in mainland China.

Objectives: To measure the advance care planning-related knowledge and attitudes of Chinese community-dwelling older adults, in the hope of presenting a specific implementation of the strategy.

Methods: We conducted a mixed-method sequential explanatory study, composed of a quantitative survey followed by qualitative interviews. The first quantitative phase included 523 community elderly individuals, who completed a validated questionnaire. After statistical analysis, a semistructured qualitative interview has been developed and conducted with 16 of them in order to help explain findings obtained in the first phase.

Results: The study was conducted with 523 community-dwelling older adults. The cognition level of advance care planning (ACP) was low, and attitude toward ACP was active. Living alone or living with a spouse (and children), have a religion, poor health condition, and life-sustaining treatment-related experience can affect how they behave with ACP. However, lack of trust in ACP, lack of life education and relevant legislation or policies, and Chinese traditional culture and emotion may impede their take-up.

Conclusions: This study indicated that the awareness and participation of ACP of community-dwelling older adults in mainland China are not enough. The influence of national conditions and culture should be fully considered during the process of ACP development.
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http://dx.doi.org/10.1177/1049909120905255DOI Listing
September 2020

Controlling the Rotational Barrier of Single Porphyrin Rotors on Surfaces.

J Phys Chem B 2020 02 31;124(6):953-960. Epub 2020 Jan 31.

Institute of Computational and Theoretical Studies & Department of Physics , Hong Kong Baptist University , Hong Kong SAR , China.

Artificial molecular machines have played an indispensable role in many chemical and biological processes in recent decades. Among all kinds of molecular machines, molecular rotor systems have attracted increasing attention. In this work, we used density functional theory (DFT) calculations to investigate the rotational behaviors of on-surface molecular rotors based on porphyrin, which is a species of molecule with wide biological and chemical compatibilities. Moreover, our comparative studies demonstrate that macrocycle metalation, supporting substrate replacement, and functional group substitutions can effectively modify the rotational barrier of porphyrin rotors. We believe that these modification methods can further guide the path to achieve highly controllable on-surface molecular rotor systems in future applications.
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http://dx.doi.org/10.1021/acs.jpcb.9b09986DOI Listing
February 2020

Light-Guided Surface Plasmonic Bubble Movement via Contact Line De-Pinning by In-Situ Deposited Plasmonic Nanoparticle Heating.

ACS Appl Mater Interfaces 2019 Dec 10;11(51):48525-48532. Epub 2019 Dec 10.

Department of Aerospace and Mechanical Engineering , University of Notre Dame , Notre Dame , Indiana 46556 , United States.

Precise spatiotemporal control of surface bubble movement can benefit a wide range of applications like high-throughput drug screening, combinatorial material development, microfluidic logic, colloidal and molecular assembly, and so forth. In this work, we demonstrate that surface bubbles on a solid surface are directed by a laser to move at high speeds (>1.8 mm/s), and we elucidate the mechanism to be the depinning of the three-phase contact line (TPCL) by rapid plasmonic heating of nanoparticles (NPs) deposited in situ during bubble movement. On the basis of our observations, we deduce a stick-slip mechanism based on asymmetric fore-aft plasmonic heating: local evaporation at the front TPCL due to plasmonic heating depins and extends the front TPCL, followed by the advancement of the trailing TPCL to resume a spherical bubble shape to minimize surface energy. The continuous TPCL drying during bubble movement also enables well-defined contact line deposition of NP clusters along the moving path. Our finding is beneficial to various microfluidics and pattern writing applications.
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http://dx.doi.org/10.1021/acsami.9b16067DOI Listing
December 2019

Genome-wide Network-assisted Association and Enrichment Study of Amyloid Imaging Phenotype in Alzheimer's Disease.

Curr Alzheimer Res 2019 ;16(13):1163-1174

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Background: The etiology of Alzheimer's disease remains poorly understood at the mechanistic level, and genome-wide network-based genetics have the potential to provide new insights into the disease mechanisms.

Objective: The study aimed to explore the collective effects of multiple genetic association signals on an AV-45 PET measure, which is a well-known Alzheimer's disease biomarker, by employing a network assisted strategy.

Methods: First, we took advantage of a dense module search algorithm to identify modules enriched by genetic association signals in a protein-protein interaction network. Next, we performed statistical evaluation to the modules identified by dense module search, including a normalization process to adjust the topological bias in the network, a replication test to ensure the modules were not found randomly , and a permutation test to evaluate unbiased associations between the modules and amyloid imaging phenotype. Finally, topological analysis, module similarity tests and functional enrichment analysis were performed for the identified modules.

Results: We identified 24 consensus modules enriched by robust genetic signals in a genome-wide association analysis. The results not only validated several previously reported AD genes (APOE, APP, TOMM40, DDAH1, PARK2, ATP5C1, PVRL2, ELAVL1, ACTN1 and NRF1), but also nominated a few novel genes (ABL1, ABLIM2) that have not been studied in Alzheimer's disease but have shown associations with other neurodegenerative diseases.

Conclusion: The identified genes, consensus modules and enriched pathways may provide important clues to future research on the neurobiology of Alzheimer's disease and suggest potential therapeutic targets.
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http://dx.doi.org/10.2174/1567205016666191121142558DOI Listing
October 2020

Quantitative Proteome Landscape of the NCI-60 Cancer Cell Lines.

iScience 2019 Nov 31;21:664-680. Epub 2019 Oct 31.

Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

Here we describe a proteomic data resource for the NCI-60 cell lines generated by pressure cycling technology and SWATH mass spectrometry. We developed the DIA-expert software to curate and visualize the SWATH data, leading to reproducible detection of over 3,100 SwissProt proteotypic proteins and systematic quantification of pathway activities. Stoichiometric relationships of interacting proteins for DNA replication, repair, the chromatin remodeling NuRD complex, β-catenin, RNA metabolism, and prefoldins are more evident than that at the mRNA level. The data are available in CellMiner (discover.nci.nih.gov/cellminercdb and discover.nci.nih.gov/cellminer), allowing casual users to test hypotheses and perform integrative, cross-database analyses of multi-omic drug response correlations for over 20,000 drugs. We demonstrate the value of proteome data in predicting drug response for over 240 clinically relevant chemotherapeutic and targeted therapies. In summary, we present a novel proteome resource for the NCI-60, together with relevant software tools, and demonstrate the benefit of proteome analyses.
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http://dx.doi.org/10.1016/j.isci.2019.10.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889472PMC
November 2019

High-throughput proteomic analysis of FFPE tissue samples facilitates tumor stratification.

Mol Oncol 2019 11 18;13(11):2305-2328. Epub 2019 Sep 18.

Division of Medical Oncology, Lucerne Cantonal Hospital and Cancer Center, Switzerland.

Formalin-fixed, paraffin-embedded (FFPE), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here, we developed a pressure cycling technology (PCT)-SWATH mass spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PCa) and diffuse large B-cell lymphoma (DLBCL) samples. We show that the proteome patterns of FFPE PCa tissue samples and their analogous fresh-frozen (FF) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PCa tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between 1 and 15 years in a biobank and show a high degree of the proteome pattern similarity between two types of histological regions in small FFPE samples, that is, punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of a certain degree of biological variations. Applying the method to two independent DLBCL cohorts, we identified myeloperoxidase, a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PCa and DLBCL have been discovered.
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http://dx.doi.org/10.1002/1878-0261.12570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822243PMC
November 2019

Transvaginal hysterotomy: A novel approach for the treatment of cesarean scar pregnancy.

Taiwan J Obstet Gynecol 2019 Jul;58(4):460-464

Department of Gynecology, Guangdong Second Provincial General Hospital, Guangzhou, China.

The objective of this study was to determine the outcome of using transvaginal hysterotomy as the first-line treatment of cesarean scar pregnancy (CSP). A literature review was performed on all eligible reports using this modality as the first-line treatment of CSP in English report. Relevant publications were obtained from the PubMed electronic database from inception to October 2018. Two hundred and fifteen cases reported in 7 articles were reviewed. The success rate of treatment was 99.5% (214/215), complication rate was 1.4% (3/215), and hysterectomy rate was 0.5% (1/215). Transvaginal hysterotomy could be considered as a good first-line treatment modality for CSP.
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http://dx.doi.org/10.1016/j.tjog.2019.05.005DOI Listing
July 2019

In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine.

Theranostics 2019 13;9(9):2475-2488. Epub 2019 Apr 13.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing, China.

Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. : To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. : Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). : Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases.
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http://dx.doi.org/10.7150/thno.31144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526001PMC
June 2020

Gold nanoparticles in cancer hyperthermia.

Panminerva Med 2021 Mar 8;63(1):88-89. Epub 2019 May 8.

Department of Biophysics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India -

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http://dx.doi.org/10.23736/S0031-0808.18.03477-8DOI Listing
March 2021

Identification of Protein Abundance Changes in Hepatocellular Carcinoma Tissues Using PCT-SWATH.

Proteomics Clin Appl 2019 01 19;13(1):e1700179. Epub 2018 Nov 19.

Westlake Institute for Advanced Study, Westlake University, Hangzhou, Zhejiang, P. R. China.

Purpose: To rapidly identify protein abundance changes in biopsy-level fresh-frozen hepatocellular carcinoma (HCC).

Experimental Design: The pressure-cycling technology (PCT) is applied and sequential window acquisition of all theoretical mass spectra (SWATH-MS) workflow is optimized to analyze 38 biopsy-level tissue samples from 19 HCC patients. Each proteome is analyzed with 45 min LC gradient. MCM7 is validated using immunohistochemistry (IHC).

Results: A total of 11 787 proteotypic peptides from 2579 SwissProt proteins are quantified with high confidence. The coefficient of variation (CV) of peptide yield using PCT is 32.9%, and the R of peptide quantification is 0.9729. Five hundred forty-one proteins showed significant abundance change between the tumor area and its adjacent benign area. From 24 upregulated pathways and 13 suppressed ones, enhanced biomolecule synthesis and suppressed small molecular metabolism in liver tumor tissues are observed. Protein changes based on α-fetoprotein expression and hepatitis B virus infection are further analyzed. The data altogether highlight 16 promising tumor marker candidates. The upregulation of minichromosome maintenance complex component 7 (MCM7) is further observed in multiple HCC tumor tissues by IHC.

Conclusions And Clinical Relevance: The practicality of rapid proteomic analysis of biopsy-level fresh-frozen HCC tissue samples with PCT-SWATH has been demonstrated and promising tumor marker candidates including MCM7 are identified.
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http://dx.doi.org/10.1002/prca.201700179DOI Listing
January 2019

Stabilizing and Organizing Bi Cu and Bi Cu Nanoclusters in Two-Dimensional Metal-Organic Networks.

Angew Chem Int Ed Engl 2018 04 24;57(17):4617-4621. Epub 2018 Mar 24.

Department of Physics, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

Multinuclear heterometallic nanoclusters with controllable stoichiometry and structure are anticipated to possess promising catalytic, magnetic, and optical properties. Heterometallic nanoclusters with precise stoichiometry of Bi Cu and Bi Cu can be stabilized in the scaffold of two-dimensional metal-organic networks on a Cu(111) surface through on-surface metallosupramolecular self-assembly processes. The atomic structures of the nanoclusters were resolved using scanning tunneling microscopy and density functional theory calculations. The nanoclusters feature highly symmetric planar hexagonal shapes and core-shell charge modulation. The clusters are arranged as triangular lattices with a periodicity that can be tuned by choosing molecules of different size. This work shows that on-surface metallosupramolecular self-assembly creates unique possibilities for the design and synthesis of multinuclear heterometallic nanoclusters.
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http://dx.doi.org/10.1002/anie.201800906DOI Listing
April 2018

Gain of function in the mouse model of a recurrent mutation p53 promotes the formation of double minute chromosomes and the oncogenic potential of p19.

Mol Carcinog 2018 02 16;57(2):147-158. Epub 2017 Nov 16.

Lab of Molecular Genetics of Aging and Tumor, Faculty of Medicine, Kunming University of Science and Technology, Kunming, Yunnan Province, China.

The mutation p53 (p53S) has been identified as one of the recurrent mutations in human cancers by TCGA database. Our in vitro data revealed the oncogenic gain of function of p53S. To understand the function of p53S in vivo, we generated the p53S knock-in mouse. The p53 mice manifested highly invasive lymphomas and metastatic sarcomas with dramatically increased double minute chromosomes. The survival curve, the incidence of tumors and the tumor spectrum of p53 mice is very similar to the p53 mouse model. The p53 mice showed delayed onset of tumorigenesis and a high metastasis rate (40%) and low loss of heterozygosity rate (2/16). The activation of CDKN2A pathway in p53 MEF and tumors, and the accumulation of p19 protein in tumor tissues suggested p19 might contribute to the accumulation of mutant p53S protein in the tumor and promote tumorigenesis. The high expression of p19 correlated with mutant p53 accumulation and tumor progression, suggesting a dual role of p19 in tumor promotion or suppression that might depend on the p53 mutation status in tumor cells. The oncogenic gain of function of this recurrent mutation p53S prompts the reconsideration of p53 mutations function that occurs at a low frequency.
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http://dx.doi.org/10.1002/mc.22737DOI Listing
February 2018

Self-assembly of a binodal metal-organic framework exhibiting a demi-regular lattice.

Faraday Discuss 2017 10;204:111-121

Department of Physics, The Hong Kong University of Science and Technology, Hong Kong, China.

Designing metal-organic frameworks with new topologies is a long-standing quest because new topologies often accompany new properties and functions. Here we report that 1,3,5-tris[4-(pyridin-4-yl)phenyl]benzene molecules coordinate with Cu atoms to form a two-dimensional framework in which Cu adatoms form a nanometer-scale demi-regular lattice. The lattice is articulated by perfectly arranged twofold and threefold pyridyl-Cu coordination motifs in a ratio of 1 : 6 and features local dodecagonal symmetry. This structure is thermodynamically robust and emerges solely when the molecular density is at a critical value. In comparison, we present three framework structures that consist of semi-regular and regular lattices of Cu atoms self-assembled out of 1,3,5-tris[4-(pyridin-4-yl)phenyl]benzene and trispyridylbenzene molecules. Thus a family of regular, semi-regular and demi-regular lattices can be achieved by Cu-pyridyl coordination.
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http://dx.doi.org/10.1039/c7fd00088jDOI Listing
October 2017

Genome-wide association and interaction studies of CSF T-tau/Aβ ratio in ADNI cohort.

Neurobiol Aging 2017 09 15;57:247.e1-247.e8. Epub 2017 May 15.

Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA; Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indianapolis, IN, USA. Electronic address:

The pathogenic relevance in Alzheimer's disease (AD) presents a decrease of cerebrospinal fluid amyloid-ß (Aß) burden and an increase in cerebrospinal fluid total tau (T-tau) levels. In this work, we performed genome-wide association study (GWAS) and genome-wide interaction study of T-tau/Aß ratio as an AD imaging quantitative trait on 843 subjects and 563,980 single-nucleotide polymorphisms (SNPs) in ADNI cohort. We aim to identify not only SNPs with significant main effects but also SNPs with interaction effects to help explain "missing heritability". Linear regression method was used to detect SNP-SNP interactions among SNPs with uncorrected p-value ≤0.01 from the GWAS. Age, gender, and diagnosis were considered as covariates in both studies. The GWAS results replicated the previously reported AD-related genes APOE, APOC1, and TOMM40, as well as identified 14 novel genes, which showed genome-wide statistical significance. Genome-wide interaction study revealed 7 pairs of SNPs meeting the cell-size criteria and with bonferroni-corrected p-value ≤0.05. As we expect, these interaction pairs all had marginal main effects but explained a relatively high-level variance of T-tau/Aß, demonstrating their potential association with AD pathology.
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http://dx.doi.org/10.1016/j.neurobiolaging.2017.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869719PMC
September 2017

DNA Binding with Acetate Bis(1,10-phenanthroline)silver(I) Monohydrate in a Solution and Metallization of Formed Structures.

Polymers (Basel) 2017 Jun 8;9(6). Epub 2017 Jun 8.

Pro-Brite Company, Sofiyskaya ul., 93, 192289 St. Petersburg, Russia.

The study of DNA interaction with the acetate bis(1,10-phenanthroline)silver(I) monohydrate in a solution is of interest both for understanding the mechanism of biological activity of silver compound and for forming ordered structures (DNA fibrils) that can be used to solve various problems in the field of nanotechnology. The analysis of changing the DNA conformation (secondary structure, persistent length and volume effects) during the interaction by the methods of UV spectroscopy with the analysis of DNA melting, circular dichroism, viscosity, flow birefringence, AFM (atomic force microscopy) and SEM (scanning electron microscopy) was performed. The formation of two types of complexes was observed. At lower concentration of compound in DNA solution, silver atoms form the coordination bonds with a macromolecule, while the released phenanthroline ligands intercalate between DNA bases. When the concentration of the compound increases, the phenanthroline ligands form an ordered "layer" around the helix. The excess of silver compounds in the DNA solution (with more than five silver atoms per base pair), DNA precipitation is observed with the formation of long fibrils. It was shown that the binding of silver to DNA during the formation of complexes provides further metallization of the resulting structures with the aid of reducing agents; phenanthroline ligands influence the result of such metallization.
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http://dx.doi.org/10.3390/polym9060211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432125PMC
June 2017

Genome-wide network-based pathway analysis of CSF t-tau/Aβ1-42 ratio in the ADNI cohort.

BMC Genomics 2017 05 30;18(1):421. Epub 2017 May 30.

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 W 16th St, Suite 4100, Indianapolis, IN, 46202, USA.

Background: The cerebrospinal fluid (CSF) levels of total tau (t-tau) and Aβ are potential early diagnostic markers for probable Alzheimer's disease (AD). The influence of genetic variation on these CSF biomarkers has been investigated in candidate or genome-wide association studies (GWAS). However, the investigation of statistically modest associations in GWAS in the context of biological networks is still an under-explored topic in AD studies. The main objective of this study is to gain further biological insights via the integration of statistical gene associations in AD with physical protein interaction networks.

Results: The CSF and genotyping data of 843 study subjects (199 CN, 85 SMC, 239 EMCI, 207 LMCI, 113 AD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed. PLINK was used to perform GWAS on the t-tau/Aβ ratio using quality controlled genotype data, including 563,980 single nucleotide polymorphisms (SNPs), with age, sex and diagnosis as covariates. Gene-level p-values were obtained by VEGAS2. Genes with p-value ≤ 0.05 were mapped on to a protein-protein interaction (PPI) network (9,617 nodes, 39,240 edges, from the HPRD Database). We integrated a consensus model strategy into the iPINBPA network analysis framework, and named it as CM-iPINBPA. Four consensus modules (CMs) were discovered by CM-iPINBPA, and were functionally annotated using the pathway analysis tool Enrichr. The intersection of four CMs forms a common subnetwork of 29 genes, including those related to tau phosphorylation (GSK3B, SUMO1, AKAP5, CALM1 and DLG4), amyloid beta production (CASP8, PIK3R1, PPA1, PARP1, CSNK2A1, NGFR, and RHOA), and AD (BCL3, CFLAR, SMAD1, and HIF1A).

Conclusions: This study coupled a consensus module (CM) strategy with the iPINBPA network analysis framework, and applied it to the GWAS of CSF t-tau/Aβ1-42 ratio in an AD study. The genome-wide network analysis yielded 4 enriched CMs that share not only genes related to tau phosphorylation or amyloid beta production but also multiple genes enriching several KEGG pathways such as Alzheimer's disease, colorectal cancer, gliomas, renal cell carcinoma, Huntington's disease, and others. This study demonstrated that integration of gene-level associations with CMs could yield statistically significant findings to offer valuable biological insights (e.g., functional interaction among the protein products of these genes) and suggest high confidence candidates for subsequent analyses.
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http://dx.doi.org/10.1186/s12864-017-3798-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450240PMC
May 2017