Eva Julià

Centre for Genomic Regulation

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Xavier Montalbán

Vall d'Hebron Institut de Recerca

Manuel Comabella

Universitat Autònoma de Barcelona

ÒF

Òscar Fornas

Pompeu Fabra University

Tomàs Marquès‐Bonet

Institut de Biologia Evolutiva

Esther Lizano

Institut de Biologia Evolutiva

David Juan

Pompeu Fabra University

Lukas F. K. Kuderna

Illumina (United States)

MÁ

Marina Álvarez-Estapé

Institut de Biologia Evolutiva

Jordi Río

Universitat Autònoma de Barcelona

Roland Martinꝉ

Karolinska Institutet

Cooperative Institutions

Pompeu Fabra University

Universitat Autònoma de Barcelona

Inserm

Centre for Genomic Regulation

Centre National de la Recherche Scientifique

Institut de Biologia Evolutiva

Vall d'Hebron Hospital Universitari

Universitat de Barcelona

Vall d'Hebron Institut de Recerca

Université Claude Bernard Lyon 1

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Fatigue in progressive multiple sclerosis is associated with low levels of dehydroepiandrosterone

Multiple Sclerosis Journal (2006)

Nieves Téllez Manuel Comabella Eva Julià Jordi Río Mar Tintoré

Fatigue is one of the most limiting symptoms in multiple sclerosis (MS) and the mechanisms underlying its origin are poorly understood. Our aim was to test whether fatigue in MS is associated with endocrine markers.We longitudinally studied 73 progressive MS patients. Fatigue was assessed at baseline and at 3, 6, 12 and 24 months using the Fatigue Severity Scale (FSS). Given the longitudinal design of our study, patients were labelled as sustained fatigued when FSS scores were >5.0 at all time points, and as non-fatigued when FSS scores were < or = 5.0 at all time points. Serum levels of dehydroepiandrosterone (DHEA), its sulphated conjugate (DHEAS) and cortisol were measured at each time point.Twenty-nine patients scored >5.0 in the FSS at all time points, and 9 patients (12.3%) scored 5.0 at all time points. Mean baseline levels of DHEAS and DHEA were lower in MS patients with sustained fatigue when compared to patients without fatigue (P = 0.01 and P = 0.03 respectively). Analysis of DHEAS and DHEA over time showed significantly lower hormone levels in patients with fatigue [F(1,31) = 6.14, P=0.019 for DHEAS; F(1,32) = 6.63, P=0.015 for DHEA].Fatigue in progressive MS could be related to low serum levels of DHEA and DHEAS. Our results suggest that these hormones should be considered as biological markers of fatigue in MS patients and that hormone replacement may thus be tested as an option to treat fatigue in MS patients.

10.1191/135248505ms1322oa

Cite

Citations (73)

Selective single molecule sequencing and assembly of a human Y chromosome of African origin

bioRxiv (Cold Spring Harbor Laboratory) (2018)

Lukas F. K. Kuderna Esther Lizano Eva Julià Jèssica Gómez‐Garrido Aitor Serres‐Armero

Mammalian Y chromosomes are often neglected from genomic analysis. Due to their inherent assembly difficulties, high repeat content, and large ampliconic regions 1 , only a handful of species have their Y chromosome properly characterized. To date, just a single human reference quality Y chromosome, of European ancestry, is available due to a lack of accessible methodology 2–5 . To facilitate the assembly of such complicated genomic territory, we developed a novel strategy to sequence native, unamplified flow sorted DNA on a MinION nanopore sequencing device. Our approach yields a highly continuous and complete assembly of the first human Y chromosome of African origin. It constitutes a significant improvement over comparable previous methods, increasing continuity by more than 800% 6 , thus allowing a chromosome scale analysis of human Y chromosomes. Sequencing native DNA also allows to take advantage of the nanopore signal data to detect epigenetic modifications in situ 7 . This approach is in theory generalizable to any species simplifying the assembly of extremely large and repetitive genomes.

Minion

Sequence assembly

Nanopore

10.1101/342667

Cite

Citations (5)

Selective single molecule sequencing and assembly of a human Y chromosome of African origin

Nature Communications (2018)

Lukas F. K. Kuderna Esther Lizano Eva Julià Jèssica Gómez‐Garrido Aitor Serres‐Armero

Abstract Mammalian Y chromosomes are often neglected from genomic analysis. Due to their inherent assembly difficulties, high repeat content, and large ampliconic regions, only a handful of species have their Y chromosome properly characterized. To date, just a single human reference quality Y chromosome, of European ancestry, is available due to a lack of accessible methodology. To facilitate the assembly of such complicated genomic territory, we developed a novel strategy to sequence native, unamplified flow sorted DNA on a MinION nanopore sequencing device. Our approach yields a highly continuous assembly of the first human Y chromosome of African origin. It constitutes a significant improvement over comparable previous methods, increasing continuity by more than 800%. Sequencing native DNA also allows to take advantage of the nanopore signal data to detect epigenetic modifications in situ. This approach is in theory generalizable to any species simplifying the assembly of extremely large and repetitive genomes.

Minion

Sequence assembly

Nanopore

10.1038/s41467-018-07885-5

Cite

Citations (84)

Plasma levels of 15d‐PGJ₂ are not altered in multiple sclerosis

European Journal of Neurology (2009)

Manuel Comabella Jesús M. Pradillo M. Fernández Jordi Río Ignacio Lizasoaín

The 15-deoxi delta prostaglandin J(2) (15d-PGJ(2)) is a peroxisome proliferator-activated receptor-gamma agonist with potent anti-inflammatory properties. It has been suggested that 15d-PGJ(2) may modulate multiple sclerosis (MS).Here, we investigated the plasma levels of 15d-PGJ(2) by enzyme-linked immunoassay in 28 healthy controls and 140 MS patients [30 patients with primary-progressive MS, 28 patients with secondary-progressive MS, and 82 patients with relapsing-remitting MS (28 patients during clinical remission, 25 patients during relapse, and 29 treated with interferon-beta - IFN-beta)].Levels of 15d-PGJ(2) were similar between healthy controls and untreated MS patients with different clinical courses of the disease. Treatment with IFN-beta had no effect on levels of 15d-PGJ(2).Although these findings suggest that 15d-PGJ(2) is not involved in the acute or chronic phases of the disease, further studies measuring 15d-PGJ(2) in cerebrospinal fluid samples are needed before excluding a role of 15d-PGJ(2) in MS.

Prostaglandin D2

10.1111/j.1468-1331.2009.02696.x

Cite

Citations (8)

Differential susceptibility to apoptosis of CD4+T cells expressing CCR5 and CXCR3 in patients with MS

Clinical Immunology (2009)

Eva Julià M.C. Edo Alejandro Horga Xavier Montalbán Manuel Comabella

CXCR3

10.1016/j.clim.2009.08.012

Cite

Citations (18)

A type I interferon signature in monocytes is associated with poor response to interferon-β in multiple sclerosis

Brain (2009)

Manuel Comabella Jan D. Lünemann Jordi Río Álex Sánchez‐Pla Cristina López

The effect of interferon-beta in multiple sclerosis is modest and many patients do not respond to treatment. To date, no single biomarker reliably correlates with responsiveness to interferon-β in multiple sclerosis. In the present study, genome-wide expression profiling was performed in peripheral blood mononuclear cells from 47 multiple sclerosis patients treated with interferon-β for a minimum of 2 years and classified as responders and non-responders based on clinical criteria. A validation cohort of 30 multiple sclerosis patients was included in the study to replicate gene-expression findings. Before treatment, interferon-β responders and non-responders were characterized by differential expression of type I interferon-induced genes with overexpression of the type interferon-induced genes in non-responders. Upon treatment the expression of these genes remained unaltered in non-responders, but was strongly upregulated in responders. Functional experiments showed a selective increase in phosphorylated STAT1 levels and interferon receptor 1 expression in monocytes of non-responders at baseline. When dissecting this type I interferon signature further, interferon-β non-responders were characterized by increased monocyte type I interferon secretion upon innate immune stimuli via toll-like receptor 4, by increased endogenous production of type I interferon, and by an elevated activation status of myeloid dendritic cells. These findings indicate that perturbations of the type I interferon signalling pathway in monocytes are related to lack of response to interferon-β, and type I interferon-regulated genes may be used as response markers in interferon-β treatment.

Interferon type I

STAT1

10.1093/brain/awp228

Cite

Citations (197)

CHROMATIN ACCESSIBILITY PROFILING TO INCREASE DIAGNOSTIC ACCURACY AND REFINE CELL‐OF‐ORIGIN CLASSIFICATION OF MATURE T‐CELL LYMPHOMAS

Hematological Oncology (2023)

Eva Julià Sylvain Mareschal Amel Chebel Camille Grandmougin E. Missaglia

Mature T-cell neoplasms (MTCN) are heterogeneous diseases with dismal prognosis. Differentiating between the many entities requires specialized pathology expertise, and studies show up to 30% of minor or major diagnostic reclassifications following expert review of cases. Assay for transposase-accessible chromatin sequencing (ATAC-seq) is a simple technique to profile open chromatin regions, which has been shown to be highly discriminative for clustering solid tumors and acute myeloid leukemias. We applied ATAC-seq to MTCN to explore the epigenetic landscape of these different entities, and built a predictive model to aid in diagnosis. FACS-sorted tumor cells from primary MTCN samples and 50µm sections of frozen tumor tissue from the French TENOMIC T-cell lymphoma consortium were processed according to previously published FAST- and OMNI-ATAC protocols, respectively. In parallel, we applied FAST-ATAC to several normal T and NK cell subsets sorted from PBMC or lymph node suspensions of healthy donors. Sequencing data were processed by an adapted version of the ENCODE ATAC-seq pipeline using a custom Hg38 genome version including HTLV1 sequence. A total of 678 normal and tumor samples were sequenced to provide a comprehensive landscape of chromatin accessibility in MTCN. Unsupervised clustering of normal NK and T cell subtypes (N = 49) and sorted tumoral lymphoma cells (N = 104) confirmed that AITL are derived from TFH cells, HSTL and LGL are closely segregated with NK and gd-T cells. We also found that T-PLL likely derive from the transformation of naïve T cells. Epigenetic profiling by ATAC-seq of FACS-sorted tumor samples resulted in a complete segregation of the known MTCN entities (TFH, ALK+ and ALK- ALCL, HSTL, CTCL, ATLL, LGL and T-PLL). Most PTCL-NOS (13/17) clustered with a predefined MTCN subtype (mainly AITL/TFH-phenotype PTCL, CTCL and lymphomas exhibiting cytotoxic features), showing that this waste basket subgroup is merely virtual, at least from an epigenetic point of view. Using unsupervised deconvolution approaches, we were able to discriminate different MTCN subtypes from 223 processed frozen bulk samples. All known MTCN subtypes were identified by ATAC-seq but a novel subset of PTCL-NOS representing ∼5% of cases was pinpointed, showing high GATA3 transcription factor activity. Subsequent exome sequencing revealed numerous copy number alterations and TP53 (8/12) and NCOR1 mutations (7/12). A support vector machine model was trained to predict diagnosis and showed accurate classification performance by cross-validation and on external validation cohort collected from 5 tertiary care centers. ATAC-seq is a rapid and cost-effective technique with high classification accuracy for PTCL subtypes. Among GATA3-expressing PTCL that spread across multiple epigenetic subgroups, we identified a specific entity with recurrent NCOR1 mutations. Keywords: aggressive T-cell non-Hodgkin lymphoma, genomics, epigenomics, and other -omics, pathology and classification of lymphomas No conflicts of interests pertinent to the abstract.

Massive parallel sequencing

Single-Cell Analysis

10.1002/hon.3163_123

Cite

Citations (0)

A New Chromosome-Assigned Mongolian Gerbil Genome Allows Characterization of Complete Centromeres and a Fully Heterochromatic Chromosome

Molecular Biology and Evolution (2023)

Thomas D. Brekke Alexander S. T. Papadopulos Eva Julià Òscar Fornas Beiyuan Fu

Abstract Chromosome-scale genome assemblies based on ultralong-read sequencing technologies are able to illuminate previously intractable aspects of genome biology such as fine-scale centromere structure and large-scale variation in genome features such as heterochromatin, GC content, recombination rate, and gene content. We present here a new chromosome-scale genome of the Mongolian gerbil (Meriones unguiculatus), which includes the complete sequence of all centromeres. Gerbils are thus the one of the first vertebrates to have their centromeres completely sequenced. Gerbil centromeres are composed of four different repeats of length 6, 37, 127, or 1,747 bp, which occur in simple alternating arrays and span 1–6 Mb. Gerbil genomes have both an extensive set of GC-rich genes and chromosomes strikingly enriched for constitutive heterochromatin. We sought to determine if there was a link between these two phenomena and found that the two heterochromatic chromosomes of the Mongolian gerbil have distinct underpinnings: Chromosome 5 has a large block of intraarm heterochromatin as the result of a massive expansion of centromeric repeats, while chromosome 13 is comprised of extremely large (>150 kb) repeated sequences. In addition to characterizing centromeres, our results demonstrate the importance of including karyotypic features such as chromosome number and the locations of centromeres in the interpretation of genome sequence data and highlight novel patterns involved in the evolution of chromosomes.

Constitutive heterochromatin

Repeated sequence

10.1093/molbev/msad115

Cite

Citations (7)

Y chromosome sequence and epigenomic reconstruction across human populations

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Paula Esteller-Cucala Marc Palmada‐Flores Lukas F. K. Kuderna Claudia Fontsere Aitor Serres‐Armero

Abstract Recent advances in long-read sequencing technologies have allowed the generation and curation of more complete genome assemblies, enabling the analysis of traditionally neglected chromosomes, such as the human Y chromosome (chrY). Native DNA was sequenced on a MinION Oxford Nanopore Technologies sequencing device to generate genome assemblies for 7 major chrY human haplogroups. We analyzed and compared the chrY enrichment of sequencing data obtained using two different selective sequencing approaches: adaptive sampling and flow cytometry chromosome sorting. We show that adaptive sampling can produce data to create assemblies comparable to chromosome sorting while being a less expensive and time-consuming technique. We also assessed haplogroup-specific structural variants, which would be otherwise difficult to study using short-read sequencing data only. Finally, we took advantage of this technology to detect and profile epigenetic modifications amongst the considered haplogroups. Altogether, we provide a framework to study complex genomic regions with a simple, fast, and affordable methodology that could be applied to larger population genomics datasets.

Haplogroup

Minion

Epigenomics

10.1101/2022.12.02.518894

Cite

Citations (0)

Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

Journal of Neuroimmunology (2006)

Eva Julià Xavier Montalbán Hammad Alzayat Shohreh Issazadeh‐Navikas Robert Goertsches

CXCR3

Pathogenesis

Fas ligand

CD69

10.1016/j.jneuroim.2006.07.001

Cite

Citations (18)