Biology subjects

Berman, B. P.

Publications and source records attributed to Berman, B. P..

At least 19 recordsLinked to original sources

bioRxiv2026

Improved deconvolution of circulating tumor DNA from ultra-low-pass whole-genome methylation sequencing using CelFiE-ISH

Liquid biopsy using ultra-low-pass whole-genome sequencing (ULP-WGS, [~]0.25x coverage) is a promising tool to detect circulating tumor DNA (ctDNA) for cancer management, and the use of the native Oxford Nanopore (ONT) sequencing platform adds DNA methylation to the set of detectable features. Here, we test the performance of methylation-based cell-type deconvolution in ULP-WGS samples from diverse epithelial malignancies and investigate several new computational strategies using our CelFiE-ISH deconvolution framework. We find that incorporating larger numbers of markers restricted to the epithelial cell lineage can reduce the cancer fraction limit of detection down to 1.7-3.1%, matching or exceeding the 3% floor of established copy-number alteration (CNA) benchmarks. Our study provides a useful strategy for analysis of ULP-WGS ONT data and indicates that marker selection remains a key challenge for analyzing methylation-based cancer datasets.

genomics↗

bioRxiv2026

Cytokine-induced Chromatin Accessibility in Whole Blood Neutrophils Links to Sepsis Transcriptional 1 States

BackgroundNeutrophils play an important role in the immune system and sense environmental perturbations including pathogens. Upon pathogen detection, neutrophils extrude their chromatin, forming neutrophil extracellular traps (NETs) trapping and removing pathogens. Previous studies have shown that controlled chromatin decondensation occurs during NET formation, reflecting NET inducing pathways, and the cellular environment. While NET inducing stimuli like phorbol 12-myristate 13-acetate (PMA) is commonly used to study NET formation, it bypassing regulatory mechanisms, limiting insights. MethodsWe used the Assay for Transposase-Accessible Chromatin with sequencing (ATAC-Seq) to profile chromatin accessibility in neutrophils stimulated in whole blood with PMA and physiologically relevant inflammatory factors (NFs), including TNF-, GM-CSF, fMLP, C5a, and IL-1{beta}, alone and in combination. Chromatin responses were compared across conditions and integrated with publicly available transcriptomic sepsis cohorts. ResultsWe found that NF stimulation induced stimulus specific chromatin accessibility programs distinct from PMA. Individual NFs increased specific transcription factor (TF) motif enrichments in a stimulus dependent manner, with GM-CSF increasing STATs, TNF- increasing NF-{kappa}B, C5a/fMLP increasing AP-1, and Combined with a cooperative response including CEBP. Integration with sepsis transcriptomic datasets revealed that promoter accessibility changes within NF stimulations correspond to transcriptional states associated with sepsis disease severity, highlighting the upstream regulatory programs linked to clinical outcomes. ConclusionsThese findings demonstrate that NF stimulation in whole blood reveals chromatin accessibility programs in neutrophils that correlate with disease severity in sepsis. This approach provides a framework for linking cytokine driven neutrophil regulation to heterogenous inflammatory states in sepsis and other NET-associated diseases.

immunology↗

bioRxiv2025

Chromatin Changes Associated with Neutrophil Extracellular Trap (NET) Formation in Whole Blood Reflect Complex Immune Signaling

BackgroundNeutrophils are key players in innate immunity, forming neutrophil extracellular traps (NETs) to defend against infections. However, excess NET formation is implicated in inflammatory conditions such as sepsis and immunothrombosis. Studying NET formation in isolated neutrophils provides important mechanistic insights but does not reflect the complexity of immune interactions in whole blood, limiting our understanding of neutrophil responses. MethodsThis study investigates chromatin accessibility changes using Assay for Transposase-Accessible Chromatin with sequencing (ATAC-Seq) during phorbol 12-myristate 13-acetate (PMA) induced NET formation in whole blood. We compared chromatin accessibility patterns in neutrophils following PMA treatment in isolation and whole blood to assess the impact of other immune cells and signaling environment. ResultsWhole blood PMA stimulation elicited consistent chromatin accessibility changes across donors, demonstrating organized chromatin decondensation during NET formation. The chromatin response was characterized by increased accessibility in genomic regions enriched for immune-specific pathways, highlighting the role of immune cell interactions in NET formation. Differentially accessible regions (DARs) present following PMA induction in whole blood and isolated neutrophils showed greater association with NET-related and inflammatory transcription factors, while DARs specific to isolated neutrophils showed fewer relevant motifs. Pathway analysis indicated that whole blood responses involved more robust activation of immune-specific pathways, such as interleukin and cytokine signaling, compared to isolated neutrophils. ConclusionsOur findings underscore the importance of studying NET formation within a whole blood environment to capture the complexity of neutrophil responses and immune cell interactions. This understanding is crucial for identifying effective therapeutic targets in NET-associated inflammatory diseases.

immunology↗

bioRxiv2024

Understanding Complex Chromatin Dynamics of Primary Human Neutrophils During PMA Induced NETosis

BackgroundPrimary human neutrophils play a pivotal role in innate immunity, mainly through the formation of neutrophil extracellular traps (NETs) in a process known as NETosis. This cell-death pathway is crucial for combating infections but is also implicated in many inflammatory diseases such as sepsis, systemic lupus erythematosus, rheumatoid arthritis, and others. MethodsThe study presented here investigates chromatin dynamics during NETosis by stimulating primary human neutrophils with phorbol 12-myristate 13-acetate (PMA). We adapt the ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) method to isolated neutrophils and characterize a time-dependent chromatin response. ResultsWe find that chromatin accessibility patterns are consistent across individual donors and most chromatin changes occur within 30 minutes, with many continuing across the 90 minutes assessed in this study. Regulatory regions gaining accessibility are associated with activity of pathways that have been implicated in NOX-dependent NET formation. ConclusionsOur findings enhance the understanding of the chromatin changes underlying NETosis and also identify potential early-acting targets for modulating this process in inflammatory diseases.

immunology↗

bioRxiv2024

Long-read sequencing reveals aberrant fragmentation patterns and origins of circulating DNA in cancer

Circulating cell-free DNA (cfDNA) carries fragmentation patterns that serve as biomarkers of cancer, but standard sequencing approaches miss large portions of the fragment length spectrum. In addition to altered fragmentation patterns, cancer patients often have elevated levels of cfDNA, but the underlying mechanisms are not well understood. To address both questions, we analyzed cancer cases with elevated cfDNA levels using Oxford Nanopore (ONT) sequencing. Long-read ONT sequencing captures the full spectrum of cfDNA fragment lengths and enables cell type inference based on DNA methylation markers. One cohort included cases from several cancer types with elevated cfDNA levels, and a second consisted of patients from a single neuroendocrine cancer study. In each cohort, cases with the highest cfDNA levels showed either hypofragmentation (excess fragments of 1-4 kb) or hyperfragmentation (excess fragments <145 bp). Hypofragmentation reflected blood cell DNA released during delayed sample processing, bearing DNASE1L3-associated hallmarks, while in one cohort we also observed ultra-long fragments (>7.5 kb) lacking these hallmarks and consistent with plasma lysis. By contrast, hyperfragmented samples often had elevated levels of both cancer- and blood-derived DNA, indicating an inflammatory or other system process rather than cancer-specific origin. These findings clarify the distinction between biological and artifactual fragmentation, expand our understanding of cfDNA biology, and highlight long-read sequencing as a powerful tool for biomarker discovery.

cancer biology↗

bioRxiv2023

Multi-cell type deconvolution using a probabilistic model for single-molecule DNA methylation haplotypes

BackgroundDeconvolution is used to estimate the proportion of mixed cell types from tissue or blood samples based on genomic profiling. DNA methylation is commonly used because specific CpG positions reflect cell type identity and can be accurately measured at either the population or single-molecule level. Methylation sequencing techniques can profile multiple individual CpGs on a single DNA molecule, but few deconvolution models have been developed to exploit these single-molecule methylation haplotypes for cell type deconvolution. Results and ConclusionsWe used simulated whole-genome methylation data and in silico mixtures of real data to compare existing deconvolution tools with two new models developed here. We found that adapting an existing model CelFiE to incorporate methylation haplotype information improved deconvolution accuracy by [~]30% over other tools, including the original CelFiE. In addition to overall higher accuracy, our new tool CelFiE Integrated Single-molecule Haplotypes (or CelFiE-ISH) outperformed others in detecting rare cell types present at 0.1% and below. Detection of rare cell types is important for the analysis of circulating DNA, which we demonstrate using a patient-derived plasma sequencing dataset.Finally,we show that marker selection strategy has a strong effect on deconvolution accuracy, concluding that haplotype-aware deconvolution can take advantage of markers tailored for that purpose.

bioinformatics↗

bioRxiv2022

Comprehensive analyses of partially methylated domains and differentially methylated regions in esophageal cancer reveal both cell-type- and cancer-specific epigenetic regulation

As one of the most common malignancies, esophageal cancer has two subtypes, squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), arising from distinct cells-of-origin. However, distinguishing cell-type-specific molecular features from cancer-specific characteristics has been challenging. Here, we analyze whole-genome bisulfite sequencing (WGBS) data on 45 esophageal tumor and nonmalignant samples from both subtypes. We develop a novel sequence-aware method to identify large partially methylated domains (PMDs), revealing profound heterogeneity at both the methylation level (depth) and genomic distribution (breadth) of PMDs across tumor samples. We identify subtype-specific PMDs, which are associated with repressive transcription, chromatin B compartments and high somatic mutation rate. While the genomic locations of these PMDs are pre-established in normal cells, the degree of loss is significantly higher in tumors. We find that cell-type-specific deposition of H3K36me2 may underlie the genomic distribution PMDs. At a smaller genomic scale, both cell-type- and cancer-specific differentially methylated regions (DMRs) are identified for each subtype. Using binding motif analysis within these DMRs, we show that a cell-type-specific transcription factor such as HNF4A can maintain the binding sites that it establishes in normal cells, while being recruited to new binding sites with novel partners such as FOSL1 in cancer. Finally, leveraging pan-tissue single-cell and pan-cancer epigenomic datasets, we demonstrate that a substantial fraction of the cell-type-specific PMDs and DMRs identified here in esophageal cancer, are actually markers that co-occur in other cancers originating from related cell types. These findings advance our understanding of the DNA methylation dynamics at various genomic scales in normal and malignant states, providing novel mechanistic insights into cell-type- and cancer-specific epigenetic regulations.

cancer biology↗

bioRxiv2022

A local sequence signature defines a subset of heterochromatin-associated CpGs with minimal loss of methylation in healthy tissues but extensive loss in cancer

Global loss of DNA methylation in mammalian genomes occurs during aging and cancer, primarily in heterochromatin-associated Partially Methylated Domains (PMDs). It has previously been shown that local sequence context (100bp) has a strong influence on the rate of demethylation of individual CpG dinucleotides within PMDs. Here, we train a deep learning model to capture this sequence dependence, finding that methylation loss in healthy tissues and cancer can be predicted with high accuracy based on the 150bp surrounding a CpG. We use a published whole-genome map of the re-methylation rate of newly synthesized DNA during mitosis to show that CpGs with a "slow-loss" sequence context are efficiently re-methylated, while CpGs with a "fast-loss" sequence context are inefficiently re-methylated. Intriguingly, we find that the 10% most slow-loss CpGs lose almost no DNA methylation in healthy cell types, but lose significant DNA methylation in many cancer types. This finding suggests that loss of DNA methylation at slow-loss CpGs could underlie some cancer-specific transcriptional deregulation that has been linked to DNA hypomethylation, including the derepression of cancer antigens and transposable elements.

genomics↗

bioRxiv2021

Detecting cell-of-origin and cancer-specific features of cell-free DNA with Nanopore sequencing

The Oxford Nanopore (ONT) platform provides portable and rapid genome sequencing, and its ability to natively profile DNA methylation without complex sample processing is attractive for clinical sequencing. We recently demonstrated ONT shallow whole-genome sequencing to detect copy number alterations (CNA) from the circulating tumor DNA (ctDNA) of cancer patients. Here, we show that cell-type and cancer-specific methylation changes can also be detected, as well as cancer-associated fragmentation signatures. This feasibility study suggests that ONT shallow WGS could be a powerful tool for liquid biopsy, especially real-time medical applications.

genomics↗

bioRxiv2021

Validation of Data Acquisition and Phase Estimation for Quantitative Susceptibility Mapping with a Rotating-Tube Phantom

PurposeQuantitative Susceptibility Mapping (QSM) is an MRI tool with the potential to reveal pathological changes from magnetic susceptibility measurements. Before phase data can be used to recover susceptibility ({Delta}{chi}), the QSM process begins with two steps: data acquisition and phase estimation. We assess the performance of these steps, when applied without user intervention, on several variations of a phantom imaging task. ApproachWe used a rotating-tube phantom with five tubes ranging from {Delta}{chi}=0.05 ppm to {Delta}{chi}=0.336 ppm. MRI data was acquired at nine angles of rotation for four different pulse sequences. The images were processed by 10 phase estimation algorithms including Laplacian, region-growing, branch-cut, temporal unwrapping and maximum-likelihood methods. We analyzed errors between measured and expected phase using the probability mass function and Cumulative Distribution Function. ResultsRepeatable acquisition and estimation methods were identified based on the probability of relative phase errors. For single-echo GRE and segmented EPI sequences, a region-growing method was most reliable with Pr(relative error<0.1)=0.95 and 0.90 respectively. For multi-echo sequences, a Maximum-Likelihood method was most reliable with Pr(relative error<0.1)=0.97. The most repeatable multi-echo methods outperformed the most repeatable single-echo methods. ConclusionsWe found a wide range of repeatability and reproducibility for off-the-shelf MRI acquisition and phase estimation approaches. The error was dominated in many cases by spatially discontinuous phase unwrapping errors. Any post-processing applied on erroneous phase estimates, such as QSMs background field removal and dipole inversion, would suffer from error propagation. Our paradigm identifies methods that yield consistent and accurate phase estimates that would ultimately yield consistent and accurate {Delta}{chi} estimates.

bioengineering↗

bioRxiv2021

Expanding the MECP2 network using comparative genomics reveals potential therapeutic targets for Rett syndrome

Inactivating mutations in the Methyl-CpG Binding Protein 2 (MECP2) gene are the main cause of Rett syndrome (RTT). Despite extensive research into MECP2 function, no treatments for RTT are currently available. Here we use an evolutionary genomics approach to construct an unbiased MECP2 gene network, using 1,028 eukaryotic genomes to prioritize proteins with strong co-evolutionary signatures with MECP2. Focusing on proteins targeted by FDA approved drugs led to three promising candidates, two of which were previously linked to MECP2 function (IRAK, KEAP1) and one that was not (EPOR). We show that each of these compounds has the ability to rescue different phenotypes of MECP2 inactivation in cultured human neural cell types, and appear to act on Nuclear Factor Kappa B (NF-{kappa}B) signaling in inflammation. This study highlights the potential of comparative genomics to accelerate drug discovery, and yields potential new avenues for the treatment of RTT. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/431162v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1d7e0f8org.highwire.dtl.DTLVardef@1f2c602org.highwire.dtl.DTLVardef@1a5dd7dorg.highwire.dtl.DTLVardef@7071c8_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2020

DNA methylation landscapes of matched primary and recurrent high grade serous ovarian cancers are preserved throughout disease progression and chemoresistance.

Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). We performed whole genome bisulfite sequencing (WGBS) and whole transcriptome sequencing (RNA-seq) to establish methylation and gene expression signatures in 62 primary and recurrent tumors from 28 patients diagnosed with stage III/IV HGSOC. Eleven of these patients carried pathogenic germline BRCA1/BRCA2 mutations. Genome-wide methylation and transcriptomic features identified in primary tumors were largely preserved in matched recurrent tumors from the same patient (P-value = 7.16 x 10-7 and 1.41 x 10-3 in BRCA1/2 and non-BRCA1/2 cases respectively). Tumors from BRCA1/2 carriers displayed high levels of heterogeneity, with significantly more shared methylation changes identified between primary and recurrent tumors from non-BRCA1/2 patients, which may be related to the poorer survival we observe in HGSOCs from non-BRCA1/2 carriers (P-value = 0.0056). Partially methylated domains (PMDs) dominated the epigenetic variation across all tumors, and were more hypomethylated in BRCA1/2 than non-BRCA1/2 cases. Differential gene expression analysis identified upregulation of genes from immune pathways including antigen processing and presentation in tumors from BRCA1/2 carriers, implicating increased immune response in the improved survival observed in these patients. In summary, this study shows a previously unreported conservation of methylation and gene expression in recurrent HGSOCs. These data have implications for the possible effectiveness of epigenetic based therapies to treat both primary and recurrent ovarian cancers.

genomics↗

bioRxiv2020

A pan-cancer analysis of CpG Island gene regulation reveals extensive plasticity within Polycomb targets

CpG Island promoter genes make up more than half of human genes, and a subset regulated by Polycomb-Repressive Complex 2 (PRC2+-CGI) become DNA methylated and silenced in cancer. Here, we perform a systematic regulatory analysis of CGI genes across TCGA cancer types, finding that PRC2+-CGI genes are frequently prone to transcriptional upregulation as well. These upregulated PRC2+-CGI genes control important pathways such as Epithelial-Mesenchymal Transition and TNF-associated inflammatory response, and have the greatest cancer-type specificity among any class of CGI genes. Using publicly available chromatin datasets and genetic perturbations, we show that transcription factor binding sites (TFBSs) within distal enhancers underlie transcriptional activation of PRC2+-CGI genes, in contrast to PRC2-free CGI genes which are predominantly regulated by promoter TFBSs. Surprisingly, a large subset of PRC2+-CGI genes that are upregulated in one cancer type are also hypermethylated/silenced in at least one other cancer type, highlighting the high degree of regulatory plasticity likely derived from their complex regulatory patterns during normal development.

cancer biology↗

bioRxiv2020

Ovarian Cancer Risk Variants are Enriched in Histotype-Specific Enhancers that Disrupt Transcription Factor Binding Sites

Quantifying the functional effects of complex disease risk variants can provide insights into mechanisms underlying disease biology. Genome wide association studies (GWAS) have identified 39 regions associated with risk of epithelial ovarian cancer (EOC). The vast majority of these variants lie in the non-coding genome, suggesting they mediate their function through the regulation of gene expression by their interaction with tissue specific regulatory elements (REs). In this study, by intersecting germline genetic risk data with regulatory landscapes of active chromatin in ovarian cancers and their precursor cell types, we first estimated the heritability explained by known common low penetrance risk alleles. The narrow sense heritability [Formula] of both EOC overall and high grade serous ovarian cancer (HGSOCs) was estimated to be 5-6%. Partitioned SNP-heritability across broad functional categories indicated a significant contribution of regulatory elements to EOC heritability. We collated epigenomic profiling data for 77 cell and tissue types from public resources (Roadmap Epigenomics and ENCODE), and H3K27Ac ChIP-Seq data generated in 26 ovarian cancer-relevant cell types. We identified significant enrichment of risk SNPs in active REs marked by H3K27Ac in HGSOCs. To further investigate how risk SNPs in active REs influence predisposition to ovarian cancer, we used motifbreakR to predict the disruption of transcription factor binding sites. We identified 469 candidate causal risk variants in H3K27Ac peaks that break TF motifs (enrichment P-Value < 1x10-5 compared to control variants). The most frequently broken motif was REST (P-Value = 0.0028), which has been reported as both a tumor suppressor and an oncogene. These systematic functional annotations with epigenomic data highlight the specificity of the regulatory landscape and demonstrate functional annotation of germline risk variants is most informative when performed in highly relevant cell types.

genetics↗

bioRxiv2019

Lineage-Specific Epigenomic and Genomic Activation of the Oncogene HNF4A Promotes Gastrointestinal Adenocarcinomas

BackgroundsGastrointestinal adenocarcinomas (GIACs) of the tubular GI tract including esophagus, stomach, colon and rectum comprise most GI cancers and share a spectrum of genomic features. However, the unified epigenomic changes specific to GIACs are less well-characterized.We applied mathematical algorithms to large-scale DNA methylome and transcriptome profiles to reconstruct transcription factor (TF) networks using 907 GIAC samples from The Cancer Genome Atlas (TCGA). Complementary epigenomic technologies were performed to investigate HNF4A activation, including Circularized Chromosome Conformation Capture (4C), Chromatin immunoprecipitation (ChIP) sequencing, Whole Genome Bisulfite Sequencing (WGBS), and Assay for Transposase-Accessible Chromatin (ATAC) sequencing. In vitro and in vivo cellular phenotypical assays were conducted to study HNF4A functions.\n\nResultsWe identified a list of functionally hyperactive master regulator (MR)TFs shared across different GIACs. As the top candidate, HNF4A exhibited prominent genomic and epigenomic activation in a GIAC-specific manner. We further characterized a complex interplay between HNF4A promoter and three distal enhancer elements, which was coordinated by GIAC-specific MRTFs including ELF3, GATA4, GATA6 and KLF5. HNF4A also self-regulated its own promoter and enhancers. Functionally, HNF4A promoted cancer proliferation and survival by transcriptionally activating many downstream targets including HNF1A and factors of Interleukin signaling in a lineage-specific manner.\n\nConclusionWe use a large cohort of patient samples and an unbiased mathematical approach to highlight lineage-specific oncogenic MRTFs, which provide new insights into the GIAC-specific gene regulatory networks, and identify potential therapeutic strategies against these common cancers.

cancer biology↗

bioRxiv2019

Non-coding Somatic Mutations Converge on the PAX8 Pathway in Epithelial Ovarian Cancer

Transcriptional regulation is highly disease and cell-type specific. We performed H3K27ac chromatin immunoprecipitation and transcriptomic sequencing in primary tumors for the four different subtypes of invasive epithelial ovarian cancer (OC). Histotype-specific regulatory elements (REs) were enriched in enhancers (P<0.001). In silico prediction of putative target genes for histotype-specific REs identified genes (WFDC2, P=5.5x10-5) and pathways (PI3K-Akt signaling, P<0.002) known to be involved in OC development. Some genes (e.g. PAX8 and CA125) are associated with super-enhancers (SEs) in all OCs, while others are histotype-specific, including PPP1R3B which is associated with SEs specific to clear cell OC. Integrated analysis of active chromatin landscapes with somatic single nucleotide variants (SNVs) from whole genome sequencing (WGS) of 232 primary OCs identified frequently mutated REs, including the KLF6 promoter (P=8.2x10-8) and a putative enhancer at chromosome 6p22.1 (P<0.05). In high-grade serous OCs, somatic SNVs clustered in binding sites for the PAX8 binding partner TEAD4 (P=6x10-11), while the collection of cis regulatory elements associated with PAX8 was the most frequently mutated set of enhancers in OC (P=0.003). Functional analyses supported our findings: Knockdown of PPP1R3B in clear cell OC cells significantly reduced intracellular glycogen content, a signature feature of this histotype; and stable knockout of a 635 bp region in the 6p22.1 enhancer induced downregulation of two predicted target genes, ZSCAN16 and ZSCAN12 (P=6.6 x 10-4 and P=0.02). In summary, we have characterized histotype-specific epigenomic and transcriptomic landscapes in OC and defined likely functional REs based on somatic mutation analysis of ovarian tumors.

cancer biology↗

bioRxiv2017

Enhancer Linking by Methylation/Expression Relationships with the R package ELMER version 2

MotivationDNA methylation has been used to identify functional changes at transcriptional enhancers and other cis-regulatory modules (CRMs) in tumors and other disease tissues. Our R/Bioconductor package ELMER (Enhancer Linking by Methylation/Expression Relationships) provides a systematic approach that reconstructs altered gene regulatory networks (GRNs) by combining enhancer methylation and gene expression data derived from the same sample set.\n\nResultsWe present a completely revised version 2 of ELMER that provides numerous new features including an optional web-based interface and a new Supervised Analysis mode to use pre-defined sample groupings. We show that this approach can identify GRNs associated with many new Master Regulators including KLF5 in breast cancer.\n\nAvailabilityELMER v.2 is available as an R/Bioconductor package at http://bioconductor.org/packages/ELMER/

bioinformatics↗

bioRxiv2017

TCGAbiolinksGUI: A graphical user interface to analyze cancer molecular and clinical data

BackgroundThe GDC (Genomic Data Commons) data portal provides users with data from cancer genomics studies. Recently, we developed the R/Bioconductor TCGAbiolinks package, which allows users to search, download and prepare cancer genomics data for integrative data analysis. The use of this package requires users to have advanced knowledge of R thus limiting the number of users.\n\nResultsTo overcome this obstacle and improve the accessibility of the package by a wider range of users, we developed TCGAbiolinksGUI that uses shiny graphical user interface (GUI) available through the R/Bioconductor package.\n\nConclusionThe TCGAbiolinksGUI package is freely available within the Bioconductor project at http://bioconductor.org/packages/TCGAbiolinksGUI/. Links to the GitHub repository, a demo version of the tool, a docker image and PDF/video tutorials are available at http://bit.do/TCGAbiolinksDocs.

bioinformatics↗