Search

Active retrotransposons play important roles during evolution and continue to shape our genomes today, especially in genetic polymorphisms underlying a diverse set of diseases. However, studies of human retrotransposon insertion polymorphisms (RIPs) based on whole-genome deep sequencing at the population level have not been sufficiently undertaken, despite the obvious need for a thorough characterization of RIPs in the general population. Herein, we present a novel and efficient computational tool called Specific Insertions Detector (SID) for the detection of non-reference RIPs. We demonstrate that SID is suitable for high-depth whole-genome sequencing data using paired-end reads obtained from simulated and real datasets. We construct a comprehensive RIP database using a large population of 90 Han Chinese individuals with a mean ×68 depth per individual. In total, we identify 9342 recent RIPs, and 8433 of these RIPs are novel compared with dbRIP, including 5826 Alu, 2169 long interspersed nuclear element 1 (L1), 383 SVA, and 55 long terminal repeats. Among the 9342 RIPs, 4828 were located in gene regions and 5 were located in protein-coding regions. We demonstrate that RIPs can, in principle, be an informative resource to perform population evolution and phylogenetic analyses. Taking the demographic effects into account, we identify a weak negative selection on SVA and L1 but an approximately neutral selection for Alu elements based on the frequency spectrum of RIPs. SID is a powerful open-source program for the detection of non-reference RIPs. We built a non-reference RIP dataset that greatly enhanced the diversity of RIPs detected in the general population, and it should be invaluable to researchers interested in many aspects of human evolution, genetics, and disease. As a proof of concept, we demonstrate that the RIPs can be used as biomarkers in a similar way as single nucleotide polymorphisms.

We simulate paired-end reads for testing the accuracy and sensitivity of ourcomputer program for detection of transportable element (TE) insertions (also called Mobile Element Insertions, MEIs). we named the software "Specific Insertions Detector (SID)".

A few cases of cerebral cavernous malformation (CCM) have been reported in Chinese families with different mutations during the past decade. Herein, we report a case of CCM in a proband in a Chinese family, for whom the mutation type of the CCM remains to be identified. The proband of the family presented a range of clinical symptoms and features that included paralysis, aphasia, multiple lesions in the brain, and cutaneous capillary-venous malformations. PCR was performed to amplify all of the coding exons of the three CCM genes (CCM1, CCM2, and CCM3) in the proband and revealed a heterozygous T deletion in exon 15 (c.1542delT) of CCM1 gene. Targeted mutation analysis in family members demonstrated that this mutation segregated with the disease in the family. This is the first report of a heterozygous CCM1 deletion mutation. Our findings provide a new CCM gene mutation profile in a Chinese family which will be of significance in genetic counseling for CCM.

The tumor microenvironment (TME) is composed of tumor cells, as well as immune and stromal cells. Cancer cells can interact with the tumor microenvironment to suppress anticancer immunity and host inflammatory cells can modulate that immune response to the lesion. To better understand the TME across cancer types we used single-cell RNA-seq analysis of 224,330 cells from 77 patients with breast, gastric, nasopharyngeal carcinoma (NPC), diffuse large B-cell lymphoma (DLBCL), pancreatic, colorectal and lung cancer. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level to identify distinct cell clusters and subtypes. Comparison of the profile of T cells, macrophages, dendritic cells (DC), B cells, mast cells, granulocytes and cancer-associated fibroblasts (CAFs) identifies unique profiles by tumor type. Breast tumors have high numbers of macrophages, colorectal tumors are elevated for CD4+-T cells, DLBCLs are low in CAFs, gastric cancers have high levels of mast cells, lung tumors high levels of CD4+-T cells and natural killer (NK) T cells, NPC have elevated levels of B cells and DCs and pancreatic cancers high levels of CAFs and granulocytes and low levels of DC and CD8+-T cells. However, within a tumor type, there is also considerable heterogeneity. Understanding how the TME evolves and changes with therapy or predicts response to treatment and survival may provide insight into tumorigenesis and cancer progression. Note: This abstract was not presented at the meeting. Citation Format: Michael Dean, Guibo Li, Jianhua Jin, Yong Hou, Kui Wu, Shida Zhu, Hanlin Zhou, Ruqian Lv, Feng Lin, Si Liu, Shichen Dong, Lei Wang, Cuijuan Zhang, Yi Zhao. Analysis of the tumor microenvironment in seven cancer types by single-cell RNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 148.

The tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer by single-cell RNA-seq. The breast tumor microenvironment was profiled by analyzing the single-cell transcriptomes of 52,163 cells from the tumor tissues of 15 breast cancer patients. The tumor cells and immune cells from individual patients were analyzed simultaneously at the single-cell level. Among more than 40,000 tumor cells, we identified distinct cell clusters with different molecular subtypes and gene signatures in the same tumor, which revealed intra-tumor heterogeneity in breast cancer. We comprehensively profiled the functional state of T cells, macrophages, B cells, CAFs in breast cancer tumor microenvironment, which highlight the immune cell and CAF diversity in the breast cancer TME. Moreover, we analyzed intercellular communication in the breast cancer TME using a dataset of human ligand receptor pairs, which showed distinct cell interaction models across tumors. The evolution of the tumor microenvironment during clinical treatment was dissected by comparing tumor microenvironment of breast cancer pre- and post-chemotherapy. This study investigated the diversity of the cell types in the tumor microenvironment and provided information on the mechanisms of escape from clearance by immune cells in breast cancer, which could be a beneficial resource for immunotherapy development. Citation Format: Jianhua Yin, Hanlin Zhou, Chen Yan, Ruqian lv, Ting Wang, Chenyang He, Chen Huang, Yong Hou, Shida Zhu, Ling Wang, Michael Dean, Kui Wu, Hong Hu, Guibo Li. Comprehensive analysis of immune evasion in breast cancer by single-cell RNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 140.

Characterizing the evolution of clonal cell populations in tumor progression is a challenging task given pervasive intratumor heterogeneity (ITH). Bulk DNA sequencing remains the dominant technology for large cohorts, but requires computationally deconvolving clonal substructure from bulk data, an error-prone process with limited resolution. Single-cell sequencing (SCS) is a promising alternative but is not yet practical at the scales needed for large cohorts. To address limitations of both bulk and SCS approaches, we developed strategies for deconvolving ITH by combining bulk sequencing with limited SCS data with specific focus on copy number alterations (CNAs), which are amenable to low-depth SCS and particularly challenging for deconvolution. We introduce two methods based on non-negative matrix factorization (NMF) of bulk data. One method extends the NMF optimization objective with a penalty for deviation of inferred clones from small numbers of observed SCS samples. The other combines clonal deconvolution with tumor phylogeny inference, balancing deconvolution quality against a minimum evolution cost for incorporating inferred and observed single cells into a reconstruction of the history of clonal evolution. We validated the methods on a set of semi-synthetic data derived from true low-depth SCS data consisting of 393 single cells derived from three regions each of two human glioblastoma cases. These data were used to call mean copy numbers at 9934 genomic loci. We artificially mixed the data to generate synthetic bulk samples of known clonal composition and applied each method to correctly reconstruct unobserved single cells and their clonal structures from three, six, or nine semi-synthetic bulk samples plus six single cells each per trial. For three/six/nine bulk samples, we achieved mean RMSD of copy number inference of 1.507/1.483/1.406 for pure NMF without SCS, 0.657/0.641/0.588 for the phylogeny-free SCS method, and 0.479/0.497/0.462 for the phylogeny-based SCS method. RMSD of mixture fractions describing the clonal composition were 0.245/0.242/0.243 for pure NMF without SCS, 0.215/0.198/0.206 for the phylogeny-free SCS method, and 0.215/0.215/0.224 for the phylogeny-based SCS method. The results show that we can substantially improve on bulk CNA deconvolution using limited SCS data, providing a way to balance advantages of pure bulk and pure SCS. The work also supports the value of a principled evolutionary model in inferring accurate clonal structure. Citation Format: Haoyun Lei, Bochuan Lyu, E. Michael Gertz, Alejandro A. Schaeffer, Xulian Shi, Kui Wu, Guibo Li, Liqin Xu, Yong Hou, Michael Dean, Russell Schwartz. Deconvolution of copy number alterations combining bulk and single-cell genomic data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1650.

This study describes the case of a 41-year-old woman admitted for anterograde memory loss, right facial grimacing and right arm posturing that had begun 1 month previously. Cranial magnetic resonance-diffusion weighted imaging and -fluid-attenuated inversion recovery imaging revealed a hyperintense signal in the left hippocampus and right basal ganglia, but no contrast enhancement. An electroencephalogram revealed rhythmic sharp and slow waves and rhythmic θ build-ups in the left temporal area. Single-photon emission computed tomography showed increased regional blood flow perfusion in the left cerebral frontal lobe and the right basal ganglia. The cerebrospinal fluid was normal, with the exception of the presence of leucine-rich glioma-inactivated 1 (LGI1) antibodies, and LGI1 antibodies were also found in the blood serum. The presence of the antibodies, the faciobrachial dystonic seizures (FBDSs) and the memory loss indicated limbic encephalitis. After 3 months of immunotherapy, the patient was free from epileptic seizures and had undergone a partial memory restoration. FBDSs alone justify the immediate initiation of immunotherapy, even prior to laboratory confirmation of the disease, as early treatment limits the duration of the illness.

Background LINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers. Results Here, using retrotransposon capture sequencing (RC-seq), we surveyed L1 mutations in 14 tumours classified as glioblastoma multiforme (GBM) or as a lower grade glioma. In four GBM tumours, we characterised one probable endonuclease-independent L1 insertion, two L1-associated rearrangements and one likely Alu-Alu recombination event adjacent to an L1. These mutations included PCR validated intronic events in MeCP2 and EGFR. Despite sequencing L1 integration sites at up to 250× depth by RC-seq, we found no tumour-specific, endonuclease-dependent L1 insertions. Whole genome sequencing analysis of the tumours carrying the MeCP2 and EGFR L1 mutations also revealed no endonuclease-dependent L1 insertions. In a complementary in vitro assay, wild-type and endonuclease mutant L1 reporter constructs each mobilised very inefficiently in four cultured GBM cell lines. Conclusions These experiments altogether highlight the consistent absence of canonical L1 retrotransposition in GBM tumours and cultured cell lines, as well as atypical L1-associated sequence rearrangements following DNA damage in vivo. Electronic supplementary material The online version of this article (doi:10.1186/s13100-016-0076-6) contains supplementary material, which is available to authorized users.

The CFD/CSD coupling method is turning into the main research direction for the static/dynamic aeroelastic analyses. If one wants to use the method for the complex engineering aeroelastic problems, he needs to investigate the relative aeroelastic algorithms, such as the numerical computational method of unsteady aerodynamic forces, equivalent low-dimensional structural finite element model and the solution method of structural dynamic equations, data transfer technique between fluid and structure, the moving grid method, etc. Besides, he also needs to improve the computational efficiency by such as massive parallel CFD algorithm, reduced-order model (ROM) of unsteady aerodynamic forces, etc. In this paper, based on the authors’ recent investigations, the research progresses in computational aeroelastic methods and their applications to engineering problem are summarized.

The interfacial interaction between Cu substrates and Sn-3.5Ag-0.7Cu-xSb (x = 0, 0.2, 0.5, 0.8, 1.0, 1.5, and 2.0) solder alloys has been investigated under different isothermal aging temperatures of 100°C, 150°C, and 190°C. Scanning electron microscopy (SEM) was used to measure the thickness of the intermetallic compound (IMC) layer and observe the microstructural evolution of the solder joints. The IMC phases were identified by energy-dispersive x-ray spectroscopy (EDX) and x-ray diffractometry (XRD). The growth of both the Cu6Sn5 and Cu3Sn IMC layers at the interface between the Cu substrate and the solder fits a power-law relationship with the exponent ranging from 0.42 to 0.83, which suggests that the IMC growth is primarily controlled by diffusion but may also be influenced by interface reactions. The activation energies and interdiffusion coefficients of the IMC formation of seven solder alloys were determined. The addition of Sb has a strong influence on the growth of the Cu6Sn5 layer, but very little influence on the formation of the Cu3Sn IMC phase. The thickness of the Cu3Sn layer rapidly increases with aging time and temperature, whereas the thickness of the Cu6Sn5 layer increases slowly. This is probably due to the formation of Cu3Sn at the interface between two IMC phases, which occurs with consumption of Cu6Sn5. Adding antimony to Sn-3.5Ag-0.7Cu solder can evidently increase the activation energy of Cu6Sn5 IMC formation, reduce the atomic diffusion rate, and thus inhibit excessive growth of Cu6Sn5 IMCs. This study suggests that grain boundary pinning is one of the most important mechanisms for inhibiting the growth of Cu6Sn5 IMCs in such solder joints when Sb is added.

Objective The aim of the study was to investigate the impact of 60Co γ-ray on apoptosis, cell cycles and the expression of protein hypoxia-inducible factor-1α (HIF-1α) to Hep-2 cell line in the conditions of normoxia and hypoxia.

Copy number aberrations in the tumour sample of patient #2 on chr4q12. (a) Detailed view of the 4q12 region with aberrant and highly variable copy number changes in oncogenes PDGFRA, KIT, and KDR (VEGFR2). (b) altered region in the context of chromosome 4. Y-axis of both panels indicates the log10 fold-change in counts per million (CPM), X-axis indicates position on the indicated chromosome. Shaded regions indicate gaps in the chromosome reference sequence. (PDF 133 kb)

Copy number aberration of CDKN2A on chromosome 9 in patient 2. (a) Detailed view of the CDKN2A region with the regional single-copy deletion and focal deletion of both copies indicated. (b) Altered region in the context of chromosome 9. Axes and shading are as described for Additional file 3: Figure S3. (PDF 130 kb)

Copy number aberration of MECP2 on chromosome X in patient 2. (a) Detailed view of the MECP2 region with the regional single-copy amplification indicated. (b) Altered region in the context of chromosome X. Axes and shading are as described for Additional file 3: Figure S3. (PDF 135 kb)

Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ≥ 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.

An analytical solution of the governing equations of the interacting shear flows for unsteady oblique stagnation point flow is obtained. It has the same form as that of the exact solution obtained from the complete NS equations and physical analysis and relevant discussions are then presented.

Background Single-cell resequencing (SCRS) provides many biomedical advances in variations detection at the single-cell level, but it currently relies on whole genome amplification (WGA). Three methods are commonly used for WGA: multiple displacement amplification (MDA), degenerate-oligonucleotide-primed PCR (DOP-PCR) and multiple annealing and looping-based amplification cycles (MALBAC). However, a comprehensive comparison of variations detection performance between these WGA methods has not yet been performed. Results We systematically compared the advantages and disadvantages of different WGA methods, focusing particularly on variations detection. Low-coverage whole-genome sequencing revealed that DOP-PCR had the highest duplication ratio, but an even read distribution and the best reproducibility and accuracy for detection of copy-number variations (CNVs). However, MDA had significantly higher genome recovery sensitivity (~84 %) than DOP-PCR (~6 %) and MALBAC (~52 %) at high sequencing depth. MALBAC and MDA had comparable single-nucleotide variations detection efficiency, false-positive ratio, and allele drop-out ratio. We further demonstrated that SCRS data amplified by either MDA or MALBAC from a gastric cancer cell line could accurately detect gastric cancer CNVs with comparable sensitivity and specificity, including amplifications of 12p11.22 (KRAS) and 9p24.1 (JAK2, CD274, and PDCD1LG2). Conclusions Our findings provide a comprehensive comparison of variations detection performance using SCRS amplified by different WGA methods. It will guide researchers to determine which WGA method is best suited to individual experimental needs at single-cell level. Electronic supplementary material The online version of this article (doi:10.1186/s13742-015-0068-3) contains supplementary material, which is available to authorized users.

In this study, we intend to develop a high-order numerical approach using the immersed-boundary method to solve problems with complex and moving boundaries such as biological locomotion (animal swimming and flying) and biomedical flow systems. The basic idea is to use the compact finite-difference scheme to resolve the flow field and a higher-order forcing scheme to treat the immersed boundaries. In this work, the one-dimensional formulation of the numerical approach is presented and is tested extensively for its convergence. Such tests are necessary before more complicated tests in 2D/3D. An overall third-order accuracy is achieved as desired. Extension to higher dimensions is ongoing.Copyright © 2014 by ASME

This paper focuses on the numerical simulation of two-phase flow near the outlet of flat fan nozzles under low operating pressure. The moment-of-fluid (MOF) method is used for the representation of the liquid gas interface and the directional split method is used for the advection of the interface. A variable density pressure projection algorithm is used for the fluid solver and a block structured adaptive mesh refinement (AMR) method is used to locally increase the resolution near interface. The internal geometry of the nozzle is defined by three parameters: nozzle inlet diameter D, V-cut or U-cut width W and V-cut or U-cut offset H. The effects of these three parameters on the fan exit angle and pressure loss through the nozzles are studied. Experiments are conducted to validate our simulation results. Finally, we give some conclusions about the modeling of the flat fan nozzle under low operating pressure based on our study.Copyright © 2014 by ASME

Single cell genomics is a rapidly growing field with many new techniques emerging in the past few years. However, few bioinformatics tools specific for single cell genomics analysis are available. Single cell DNA/RNA sequencing data usually have low genome coverage and high amplification bias, which makes bioinformatics analysis challenging. Many current bioinformatics tools developed for bulk cell sequencing do not work well with single cell sequencing data. Here, we summarize current challenges in the bioinformatics analysis of single cell genomic DNA sequencing and single cell transcriptomes. These challenges include calling copy number variations, identifying mutated genes in tumor samples, reconstructing cell lineages, recovering low abundant transcripts, and improving the accuracy of quantitative analysis of transcripts. Development in single cell genomics bioinformatics analysis will promote the application of this technology to basic biology and medical research.

Numerical simulations are carried out to study the breakup phenomena of liquid jets issuing from nozzles into gas. Liquid gas interface is captured using the state of art moment-of-fluid (MOF) methods. Directional split method is used for the advection of the liquid-gas interface and a block structured adaptive mesh refinement method is used to locally increase the resolution in the regions of interest. The breakup of two-dimensional and three-dimensional liquid jets is investigated. The influence of jet exit velocity on the breakup is studied. Comparisons are made with theoretical solutions and good agreement is observed. The parallel efficiency test shows that the block structured framework can achieve high parallel efficiency.© 2013 ASME

11580Background: Glioblastoma (GBM) is a common intracranial tumor and the most malignant form of brain cancer in adults and results in a high global mortality. GBM displays mutational complexity b...

Background Patients with hepatocellular carcinoma frequently develop multiple anatomically separate liver tumours even at early stages of the disease, thus severely limiting the benefit of surgery. Hepatitis B virus is one of the most well recognised carcinogens causing hepatocellular carcinoma in man, and the integration of viral DNA into the host genome might sufficiently induce hepatocyte transformation. The question of whether virus integration has a role in development of multiple hepatocellular carcinomas cannot be answered until the pattern of hepatitis B virus DNA integration is better understood. We aimed to search for a potential link between viral integration and development of multiple hepatocellular carcinoma. Methods We studied a Chinese man (aged 47 years) with multiple hepatocellular carcinomas that were potentially caused by an occult hepatitis B virus infection. We combined advanced liquid-phase hybridisation and capture techniques with single-cell sequencing to analyse viral integration sites in individual cells taken from the patient. The pattern of integration of hepatitis B virus was used as a genetic marker to investigate clonal evolution in hepatocellular carcinomas and hypervascular liver metastases. The study was approved by the institutional review board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Written informed consent was obtained from the patient before recruitment, according to the regulations of the institutional review board. Findings Hepatitis serology testing showed that the patient was HBsAg negative and HBsAb positive, and hepatitis B virus DNA was undetectable in his serum samples; all of these findings are consistent with the definition of occult hepatitis B virus infection. However, we detected integration of hepatitis B virus into hepatocellular carcinoma, adjacent non-hepatocellular carcinoma tissues, and tumour thrombi from the inflow and outflow hepatic vasculature. By sequencing 270 single cells from six tumour tissues, we identified two integration sites that are recurrent among almost all HBV-integrated cells—the intergenic region of MED30–EXT1 on chromosome 8 and the intragenic region of CSMD2 on chromosome 1. The preferred integration hot spots were located in the core protein-coding gene (for MED30–EXT1 ) and the DR1 region on the HBX gene (for CSMD2 ). Additionally, the DR1 region of HBX has a preference of integrating into the intronic region of CSMD2 , resulting in a truncated HBX gene, which might alter the oncogenic transforming ability of hepatocytes. Interpretation Our findings lend support to the hypothesis that multifocal hepatocellular carcinomas are monoclonal in origin and are formed in the absence of hepatitis B virus replication. Furthermore, the sites of oncogenic viral integration are not random and occur in genes that might have important roles in carcinogenesis and metastasis. Funding Major and Special Program of National Science and Technology in Twelfth Five-year Plan of China (2012ZX10002016-004 to X-PC), Major Science Foundation of the Ministry of Health of China (201302009 to X-PC), the National Natural Science Foundation of China (31200666 and 81471612 to QC; 81202300 to H-FL, and 81372495 to X-PC), the National Basic Research Program of China (973 Program; No.2011CB809203), Chinese 863 Program (2012AA02A502, 2012AA02A201), Guangdong Innovative Research Team Program (2009010016), the Guangdong Enterprise Key Laboratory of Human Disease Genomics, and the Shenzhen Municipal Government of China (CXB201108250094A, CXB201108250096A).

Background Cancers arise through an evolutionary process in which cell populations are subjected to selection; however, to date, the process of bladder cancer, which is one of the most common cancers in the world, remains unknown at a single-cell level. Results We carried out single-cell exome sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading to two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively. Conclusions This work provides a new approach of investigating the genetic details of bladder tumoral changes at the single-cell level and a new method for assessing bladder cancer evolution at a cell-population level.

Copy number aberration of EGFR, CDKN2A, and RAB14 in patient 8. (a) Amplification of EGFR on chromosome 7 (see also Fig. 2e). (b) Amplifications on chromosome 9 including CDKN2A and RAB14. (PDF 151 kb)

Copy number aberration of EGFR, CDKN2A, and RAB14 in patient 8. (a) Amplification of EGFR on chromosome 7 (see also Fig. 2e). (b) Amplifications on chromosome 9 including CDKN2A and RAB14. (PDF 151 kb)