Cankut Cubuk

Cankut Cubuk
Centro de Investigación Príncipe Felipe | CIPF · IBIT - Computational Medicine

PhD

About

64
Publications
6,809
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628
Citations
Introduction
Cankut Cubuk currently works at the CIPF - Computational Medicine, Centro de Investigación Príncipe Felipe. Cankut does research in Systems Biology, Bioinformatics and Cancer Research. Their current project is 'Signaling pathways.'
Additional affiliations
October 2018 - present
Fundación Progreso y Salud
Position
  • Bioinformatician
November 2013 - October 2017
Centro de Investigación Príncipe Felipe
Position
  • PhD Student

Publications

Publications (64)
Article
Full-text available
Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the diseased tissue. Approximately 40% of patients do not respond to individual biologic therapies and 5–20% are refractory to all. In a biopsy-based, precision-medicine, randomized clinical trial in RA (R4RA;...
Article
Full-text available
Objectives To integrate published single-cell RNA sequencing (scRNA-seq) data and assess the contribution of synovial fibroblast (SF) subsets to synovial pathotypes and respective clinical characteristics in treatment-naïve early arthritis. Methods In this in silico study, we integrated scRNA-seq data from published studies with additional unpubli...
Article
Full-text available
Objective To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. Methods Hypervariable V3–V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, res...
Article
Full-text available
Purpose Conditions and thresholds applied for evidence-weighting of PM5 (within-codon concordance for pathogenicity) vary widely between laboratories and expert groups. Due to the sparseness of available clinical classifications, there is little evidence for variation in practice. Methods We used as a truthset 7541 dichotomous functional classific...
Article
Full-text available
Purpose Where multiple in silico tools are concordant, the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) framework affords supporting evidence toward pathogenicity or benignity, equivalent to a likelihood ratio of ~2. However, limited availability of “clinical truth sets” and prior use in tool trai...
Conference Paper
Background The study of synovial tissue in patients with Rheumatoid Arthritis (RA) has led to the identification of synovial patterns of immune cell infiltration and specific cellular subsets associated that have been disease activity and clinical outcomes( 1 – 3 ). However, the relationship of circulating and synovial immune cell sub-sets with his...
Article
Full-text available
Genome-scale mechanistic models of pathways are gaining importance for genomic data interpretation because they provide a natural link between genotype measurements (transcriptomics or genomics data) and the phenotype of the cell (its functional behavior). Moreover, mechanistic models can be used to predict the potential effect of interventions, in...
Article
Full-text available
Here we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map. In this framework, the detailed activity of the human signaling circuits related to the viral infection, covering from the entry and replication mechanisms to the downstream consequences as inflammation and antigenic response, can be inf...
Preprint
Full-text available
In the last decade, different omic technologies have experiences an exponential technological advancement. However, metabolomics has not followed a similarly vertiginous improving improvement and are far from genomics or transcriptomics in terms of throughput, cost and even accuracy. Therefore, genome-scale in-silico methodologies to estimate metab...
Article
Full-text available
Accurate classification of variants in cancer susceptibility genes (CSGs) is key for correct estimation of cancer risk and management of patients. Consistency in the weighting assigned to individual elements of evidence has been much improved by the American College of Medical Genetics (ACMG) 2015 framework for variant classification, UK Associatio...
Preprint
Full-text available
Here we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map. In this framework, the detailed activity of the human signaling circuits related to the viral infection, covering from the entry and replication mechanisms to the downstream consequences as inflammation and antigenic response, can be inf...
Preprint
Full-text available
Here we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map. In this framework, the detailed activity of the human signaling circuits related to the viral infection, covering from the entry and replication mechanisms to the downstream consequences as inflammation and antigenic response, can be inf...
Article
Full-text available
Cancer is driven by genomic alterations, but the processes causing this disease are largely performed by proteins. However, proteins are harder and more expensive to measure than genes and transcripts. To catalyze developments of methods to infer protein levels from other omics measurements, we leveraged crowdsourcing via the NCI-CPTAC DREAM proteo...
Article
Full-text available
Despite the existence of differences in gene expression across numerous genes between males and females having been known for a long time, these have been mostly ignored in many studies, including drug development and its therapeutic use. In fact, the consequences of such differences over the disease mechanisms or the drug action mechanisms are com...
Preprint
Full-text available
Here we present a web interface that implements a comprehensive mechanistic model of the SARS-CoV-2 disease map in which the detailed activity of the human signaling circuits related to the viral infection and the different antiviral responses, including immune and inflammatory activities, can be inferred from gene expression experiments. Moreover,...
Article
Full-text available
Advances in technology have led to a massive expansion in the capacity for genomic analysis, with a commensurate fall in costs. The clinical indications for genomic testing have evolved markedly; the volume of clinical sequencing has increased dramatically; and the range of clinical professionals involved in the process has broadened. There is gene...
Article
Full-text available
White adipose tissue (WAT) inflammation contributes to the development of insulin resistance in obesity. While the role of adipose tissue macrophage (ATM) pro-inflammatory signalling in the development of insulin resistance has been established, it is less clear how WAT inflammation is initiated. Here, we show that ATMs isolated from obese mice and...
Preprint
Full-text available
White adipose tissue (WAT) inflammation contributes to the development of insulin resistance in obesity. While the role of adipose tissue macrophage (ATM) pro-inflammatory signalling in the development of insulin resistance has been established, it is less clear how WAT inflammation is initiated. Here, we show that ATMs from obese mice and humans e...
Article
Full-text available
Background: Despite the progress in neuroblastoma therapies the mortality of high-risk patients is still high (40-50%) and the molecular basis of the disease remains poorly known. Recently, a mathematical model was used to demonstrate that the network regulating stress signaling by the c-Jun N-terminal kinase pathway played a crucial role in survi...
Preprint
Full-text available
In spite of the increasing availability of genomic and transcriptomic data, there is still a gap between the detection of perturbations in gene expression and the understanding of their contribution to the molecular mechanisms that ultimately account for the phenotype studied. Alterations in the metabolism are behind the initiation and progression...
Article
Full-text available
Motivation: Current plant and animal genomic studies are often based on newly assembled genomes that have not been properly consolidated. In this scenario, misassembled regions can easily lead to false positive findings. Despite quality control scores are included within genotyping protocols, they are usually employed to evaluate individual sample...
Preprint
With the advent of high-throughput technologies for genome-wide expression profiling, a large number of methods have been proposed to discover gene-based signatures as biomarkers to guide cancer prognosis. However, it is often difficult to interpret the list of genes in a prognostic signature regarding the underlying biological processes responsibl...
Article
Full-text available
Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measu...
Article
Full-text available
Background: Stress-associated conditions such as psychoemotional reactivity and depression have been paradoxically linked to either weight gain or weight loss. This bi-directional effect of stress is not understood at the functional level. Here we tested the hypothesis that pre-stress level of adaptive thermogenesis and brown adipose tissue (BAT)...
Preprint
Full-text available
Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measu...
Article
Full-text available
The discovery of actionable targets is crucial for targeted therapies and is also a constituent part of the drug discovery process. The success of an intervention over a target depends critically on its contribution, within the complex network of gene interactions, to the cellular processes responsible for disease progression or therapeutic respons...
Article
Full-text available
Chronic stress has been associated with obesity, glucose intolerance, and insulin resistance. We developed a model of chronic psychosocial stress (CPS) in which subordinate mice are vulnerable to obesity and the metabolic-like syndrome while dominant mice exhibit a healthy metabolic phenotype. Here we tested the hypothesis that the metabolic differ...
Article
Full-text available
Objective: The purpose of this study was to determine the microRNA (miRNA) profiles and the apoptosis rates in the HL-60 (promyelocytic leukemia) and Raji (Burkitt’s lymphoma) cell lines after resveratrol administration. Materials and Methods: The experimental design included four cell culture groups: group 1: HL-60 (control), group 2: HL-60 + resv...
Data
Acute social defeat-induced thermogenesis requires βAR. Energy expenditure was continuously measured with indirect calorimetry during 10 min of baseline and for 50 min after a 10 min social defeat by an aggressive CD1. A single episode of social defeat increased VO2 (A) and decreased respiratory exchange ratio (RER) in wt mice (B) (VO2, F(1,10) = 9...
Data
Stress induced molecular and morphological effects in the scWAT. A) real time PCR of beige adipocyte markers. B) Subcutaneous inguinal white adipose tissue (scWAT) morphology and distribution of adipocyte surface area of wt and β-less mice housed at 22 °C (room temperature) and wt mice housed at 30 °C. C) UCP1 and TH are virtually absent in the scW...
Data
Altered adipose organ and behavioral response to temperature in β-less mice. A) Drawing of the thermal gradient test (TGT). B) Time spent in different thermal zones in the last 20 min of the TGT when there was no difference in activity between genotypes (treatment × zones F(2,32) = 3.8, p<0.05). C) 7 Tesla MRI in two representative 3 months old β-l...
Data
Metabolic consequence of Chronic Subordination Stress in β-less and wt mice. A) Cartoon of the chronic subordination stress protocol (CSS). B) Food efficiency during the stress phase (β-less, t54 = 4.1, p < 0.01; wt 30°C, t18 = 2.6, p < 0.05). C) Fat free mass gain (wt 22°C, t34 = 2.4, p < 0.05; β-less, t54 = 4.9, p < 0.001; wt 30°C, t18 = 2.7, p <...
Data
Norepinephrine and αAR do not mediate browning in β-less mice. A) Expression of α-Adrenergic Receptors in the BAT of wt and β-less mice housed at 22 °C. B) Norepinephrine-induced UCP1 expression in differentiating brown wt and β-less pre-adipocytes. C) Novelty-induced increase in VO2 in control and stressed wt and β-less mice housed at 22°C. Data r...
Data
Purinergic system in mice BAT. A) Immuno-morphological evidence of VNUT expression in interlobar nerves and brown adipocytes in the BAT of wt mice. B) QPCR analysis of purinergic receptors in control and stressed wt and β-less mice mice housed at 22°C.
Data
Pounceau S staining on iBAT lysate. A–B) Representative western blot of wt and β-less mice presented in Figure 4. C) Representative western blot of wt and β-less mice presented in Figure 1.
Article
Full-text available
Babelomics has been running for more than one decade offering a user-friendly interface for the functional analysis of gene expression and genomic data. Here we present its fifth release, which includes support for Next Generation Sequencing data including gene expression (RNA-seq), exome or genome resequencing. Babelomics has simplified its interf...
Article
Background: Although the importance of microsatellite instability (MSI) and mismatch repair genes (MMR) is strongly established in colorectal cancer seen in the Lynch syndrome, its significance has not been fully established in Wilms tumor (WT). The aim of this study was to determine the prognostic value of MSI and MMR proteins in WT. Methods: T...

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