Bora Uyar

Bora Uyar
Max-Delbrück-Centrum für Molekulare Medizin | MDC · Berlin Institute for Medical Systems Biology

PhD

About

52
Publications
10,565
Reads
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2,177
Citations
Introduction
Additional affiliations
August 2015 - present
Max-Delbrück-Centrum für Molekulare Medizin
Position
  • Bioinformatics Scientist
November 2014 - July 2015
European Molecular Biology Laboratory
Position
  • PostDoc Position
January 2011 - November 2014
European Molecular Biology Laboratory
Position
  • PhD Student

Publications

Publications (52)
Preprint
Comprehensive genomic profiling using cancer gene panels has been shown to improve treatment options for a variety of cancer types. However, genomic aberrations detected via such gene panels don't necessarily serve as strong predictors of drug sensitivity. In this study, using pharmacogenomics datasets of cell lines, patient-derived xenografts, and...
Article
Full-text available
Tumors are complex tissues of cancerous cells surrounded by a heterogeneous cellular microenvironment with which they interact. Single-cell sequencing enables molecular characterization of single cells within the tumor. However, cell annotation—the assignment of cell type or cell state to each sequenced cell—is a challenge, especially identifying t...
Preprint
Full-text available
The use of RNA sequencing from wastewater samples is a valuable way for estimating infection dynamics and circulating lineages of SARS-CoV-2. This approach is independent from testing individuals and can therefore become the key tool to monitor this and potentially other viruses. However, it is equally important to develop easily accessible and sca...
Preprint
Full-text available
The use of RNA sequencing from wastewater samples is proven to be a valuable way for estimating infection dynamics and circulating lineages of SARS-CoV-2. This approach has the advantage of being independent from patient population testing and symptomatic disease courses. However, it is equally important to develop easily accessible and scalable to...
Preprint
Full-text available
Tumors are highly complex tissues composed of cancerous cells, surrounded by a heterogeneous cellular microenvironment. Tumor response to treatments is governed by an interaction of cancer cell intrinsic factors with external influences of the tumor microenvironment. Disentangling the heterogeneity within a tumor is a crucial step in developing and...
Preprint
Full-text available
Cancer is a complex disease with a large financial and healthcare burden on society. One hallmark of the disease is the uncontrolled growth and proliferation of malignant cells. Unlike Mendelian diseases which may be explained by a few genomic loci, a deeper molecular and mechanistic understanding of the development of cancer is needed. Such an end...
Conference Paper
Cancer is a heterogeneous collection of diseases traditionally classified by the tissue of origin. The diversity of the molecular profiles of cancers has a big impact on the way patients are diagnosed and treated, how they respond to their prescribed treatments, the duration of survival after diagnosis, and factors such as remission, recurrence, or...
Article
Full-text available
How regulatory sequences control gene expression is fundamental for explaining phenotypes in health and disease. Regulatory elements must ultimately be understood within their genomic environment and development- or tissue-specific contexts. Because this is technically challenging, few regulatory elements have been characterized in vivo. Here, we u...
Article
Full-text available
The IκB kinase (IKK)-NF-κB pathway is activated as part of the DNA damage response and controls both inflammation and resistance to apoptosis. How these distinct functions are achieved remained unknown. We demonstrate here that DNA double-strand breaks elicit two subsequent phases of NF-κB activation in vivo and in vitro, which are mechanistically...
Article
Background Acute inflammation leads to increased myelopoiesis in the bone marrow and recruitment of immune cells to respective sites of injury. Yet, in certain cases of high demand such as acute tissue damage as in acute myocardial infarction (AMI), innate immune cells can be additionally recruited from lymphoid organs such as the spleen. Monocytes...
Article
Single-cell gene expression (transcriptomics) data are becoming robust and abundant, and are increasingly used to track organisms along their life-course. This allows investigation into how aging affects cellular transcriptomes, and how changes in transcriptomes may underlie aging, including chronic inflammation (inflammaging), immunosenescence and...
Preprint
Full-text available
Understanding how regulatory sequences control gene expression is fundamental to explain how phenotypes arise in health and disease. Traditional reporter assays inform about function of individual regulatory elements, typically in isolation. However, regulatory elements must ultimately be understood by perturbing them within their genomic environme...
Preprint
Full-text available
The IκB kinase (IKK) - NF-κB pathway is activated as part of the DNA damage response and controls both resistance to apoptosis and inflammation. How these different functions are achieved remained unknown. We demonstrate here that DNA double strand breaks elicit two subsequent phases of NF-κB activation in vivo and in vitro, which are mechanistical...
Article
Full-text available
Whether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and aspects of healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of d...
Article
Full-text available
High-occupancy target (HOT) regions are segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and consequently associated...
Preprint
Whether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of different bi...
Article
Full-text available
The IκB kinase (IKK) is considered to control gene expression primarily through activation of the transcription factor NF-κB. However, we show here that IKK additionally regulates gene expression on post-transcriptional level. IKK interacted with several mRNA-binding proteins, including a Processing (P) body scaffold protein, termed enhancer of dec...
Article
Full-text available
In bioinformatics, as well as other computationally intensive research fields, there is a need for workflows that can reliably produce consistent output, from known sources, independent of the software environment or configuration settings of the machine on which they are executed. Indeed, this is essential for controlled comparison between differe...
Data
Table S5. ATAC-Seq Analysis of SSRP1 and SUPT16H Knockdown, Related to Figures 6 and S6
Data
Table S4. ChIP-Seq for SSRP1 and SUPT16H with RNA-Seq Analysis of SSRP1 and SUPT16H Knockdown, Related to Figures 6 and S6
Data
Table S2. Results of HMG-3 and HMG-4 Co-Immunoprecipitation with Subsequent Mass Spectrometry Analysis, Related to Figure S2 and STAR Methods
Data
Table S3. ChIP-Seq, ATAC-Seq, and RNA-Seq Analysis of hmg-3, hmg-4, and spt-16, Related to Figures 4, S3, and S4
Article
Many disease-causing missense mutations affect intrinsically disordered regions (IDRs) of proteins, but the molecular mechanism of their pathogenicity is enigmatic. Here, we employ a peptide-based proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find that mutations in disordered cytosolic regions o...
Article
The chromatin regulator FACT (facilitates chromatin transcription) is essential for ensuring stable gene expression by promoting transcription. In a genetic screen using Caenorhabditis elegans, we identified that FACT maintains cell identities and acts as a barrier for transcription factor-mediated cell fate reprogramming. Strikingly, FACT's role a...
Preprint
Full-text available
In bioinformatics, as well as other computationally-intensive research fields, there is a need for workflows that can reliably produce consistent output, independent of the software environment or configuration settings of the machine on which they are executed. Indeed, this is essential for controlled comparison between different observations or f...
Preprint
The chromatin regulator FACT (Facilitates Chromatin Transcription) is essential for ensuring stable gene expression by promoting transcription. In a genetic screen using C. elegans we identified that FACT maintains cell identities and acts as a barrier for transcription factor-mediated cell fate reprogramming. Strikingly, FACTs role as a reprogramm...
Preprint
Full-text available
High-occupancy target (HOT) regions are the segments of the genome with unusually high number of transcription factor binding sites. These regions are observed in multiple species and thought to have biological importance due to high transcription factor occupancy. Furthermore, they coincide with house-keeping gene promoters and the associated gene...
Working Paper
Full-text available
Mutations in intrinsically disordered regions (IDRs) of proteins can cause a wide spectrum of diseases. Since IDRs lack a fixed three-dimensional structure, the mechanism by which such mutations cause disease is often unknown. Here, we employ a proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find...
Article
Full-text available
Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the cell cycle and monitoring cell...
Article
Full-text available
In the field of RNA, the technologies for studying the transcriptome have created a tremendous potential for deciphering the puzzles of the RNA biology. Along with the excitement, the unprecedented volume of RNA related omics data is creating great challenges in bioinformatics analyses. Here, we present the RNA Centric Annotation System (RCAS), an...
Article
Full-text available
The Eukaryotic Linear Motif (ELM) resource (http://elm.eu.org) is a manually curated database of short linear motifs (SLiMs). In this update, we present the latest additions to this resource, along with more improvements to the web interface. ELM 2016 contains more than 240 different motif classes with over 2700 experimentally validated instances,...
Article
Molecular mimicry is one of the powerful stratagems that pathogens employ to colonise their hosts and take advantage of host cell functions to guarantee their replication and dissemination. In particular, several viruses have evolved the ability to interact with host cell components through protein short linear motifs (SLiMs) that mimic host SLiMs,...
Article
Full-text available
Disease mutations are traditionally thought to impair protein functionality by disrupting the folded globular structure of proteins. However, 22% of human disease mutations occur in natively unstructured segments of proteins known as intrinsically disordered regions (IDRs). This therefore implicates defective IDR functionality in various human dise...
Article
The eukaryotic cell is a bustling collection of macromolecules acting cooperatively to mediate the functions required for cell viability. Specific, context-dependent and tightly controlled physical interactions between these cellular components govern the necessary physiological processes, from cell division to cell death. The diversity of the cell...
Article
Full-text available
The eukaryotic linear motif (ELM http://elm.eu.org) resource is a hub for collecting, classifying and curating information about short linear motifs (SLiMs). For >10 years, this resource has provided the scientific community with a freely accessible guide to the biology and function of linear motifs. The current version of ELM contains ∼200 differe...
Article
Full-text available
Curation of a high-quality gene set is the critical first step in genome research, enabling subsequent analyses such as ortholog assignment, cis-regulatory element finding, and synteny detection. In this project, we have reannotated the genome of Caenorhabditis briggsae, the best studied sister species of the model organism Caenorhabditis elegans....
Article
Full-text available
Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect of the regulatory functionality of the cell. They are particularly prominent in mediating cell signaling, controlling protein turnover and directing pro...
Article
Full-text available
Traditionally, protein-protein interactions were thought to be mediated by large, structured domains. However, it has become clear that the interactome comprises a wide range of binding interfaces with varying degrees of flexibility, ranging from rigid globular domains to disordered regions that natively lack structure. Enrichment for disorder in h...
Article
Full-text available
In humans, mutations of a growing list of regulatory factor X (RFX) target genes have been associated with devastating genetics disease conditions including ciliopathies. However, mechanisms underlying RFX transcription factors (TFs)-mediated gene expression regulation, especially differential gene expression regulation, are largely unknown. In thi...
Article
Full-text available
BLAST users frequently expect to obtain homologous genes with certain similarity to their query genes. But what they get from BLAST searches are often collections of local alignments called high-scoring segment pairs (HSPs). On the other hand, most homology-based gene finders have been built using computation-intensive algorithms, without taking fu...

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Projects

Project (1)
Archived project
In bioinformatics, as well as other computationally-intensive research fields, there is a need for workflows that can reliably produce consistent output, from known sources, independent of the software environment or configuration settings of the machine on which they are executed. Indeed, this is essential for controlled comparison between different observations or for the wider dissemination of workflows. Providing this type of reproducibility and traceability, however, is often complicated by the need to accommodate the myriad dependencies included in a larger body of software, each of which generally come in various versions. Moreover, in many fields (bioinformatics being a prime example), these versions are subject to continual change due to rapidly evolving technologies, further complicating problems related to reproducibility. Here, we propose a principled approach for building analysis pipelines and managing their dependencies with GNU Guix. As a case study to demonstrate the utility of our approach, we present a set of highly reproducible pipelines called PiGx for the analysis of RNA-seq, ChIP-seq, Bisulfite-seq, and single-cell RNA-seq. All pipelines process raw experimental data, and generate reports containing publication-ready plots and figures, with interactive report elements and standard observables. Users may install these highly reproducible packages and apply them to their own datasets without any special computational expertise beyond the use of the command line. We hope such a toolkit will provide immediate benefit to laboratory workers wishing to process theirown data sets or bioinformaticians seeking to automate all, or parts of, their analyses. In the long term, we hope our approach to reproducibility will serve as a blueprint for reproducible workflows in other areas. Our pipelines, along with their corresponding documentation and sample reports, are available at http://bioinformatics.mdc-berlin.de/pigx PiGx: Reproducible genomics analysis pipelines with GNU Guix | Request PDF. Available from: https://www.researchgate.net/publication/328027339_PiGx_Reproducible_genomics_analysis_pipelines_with_GNU_Guix [accessed Oct 31 2018].