Eduardo Eyras

Eduardo Eyras
Australian National University | ANU · John Curtin School of Medical Research

PhD
Looking for industry partners to develop a project based on mRNA

About

268
Publications
44,935
Reads
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33,614
Citations
Citations since 2016
99 Research Items
10674 Citations
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201620172018201920202021202205001,0001,500
201620172018201920202021202205001,0001,500
201620172018201920202021202205001,0001,500
Additional affiliations
January 2005 - present
Pompeu Fabra University
Position
  • Professor
January 2004 - January 2005
Centre for Genomic Regulation
Position
  • PostDoc Position
August 2001 - January 2004
Wellcome Sanger Institute
Position
  • Staff

Publications

Publications (268)
Preprint
Full-text available
Algorithms developed for basecalling Nanopore signals have primarily focused on DNA to date and utilise the raw signal as the only input. However, it is known that messenger RNA (mRNA), which dominates Nanopore direct RNA (dRNA) sequencing libraries, contains specific nucleotide patterns that are implicitly encoded in the Nanopore signals since RNA...
Article
Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML), and is driven by rare therapy-resistant leukemia-initiating stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling keeps cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hy...
Article
Full-text available
Williams-Beuren syndrome (WBS) is a rare genetic multisystemic disorder characterized by mild-to-moderate intellectual disability and hypersocial phenotype, while the most life-threatening features are cardiovascular abnormalities. Nowadays, there are no pharmacological treatments to directly ameliorate the main traits of WBS. The endocannabinoid s...
Preprint
Full-text available
Long-read sequencing enables isoform-resolved detection of functionally important RNA elements, such as RNA chemical modifications, RNA secondary structure, or RNA-protein interaction sites. Importantly, the functional impact of these elements can relate to their positions relative to isoform-specific transcript features, such as start and stop cod...
Article
Full-text available
Prostate cancer (PCa) is one the leading causes of cancer-related deaths among men. Consequently, the identification of novel molecular targets for treatment is urgently needed to improve patients’ outcomes. Our group recently reported that some elements of the cellular machinery controlling alternative-splicing might be useful as potential novel t...
Article
Full-text available
Nanopore sequencing enables the efficient and unbiased measurement of transcriptomes. Current methods for transcript identification and quantification rely on mapping reads to a reference genome, which precludes the study of species with a partial or missing reference or the identification of disease-specific transcripts not readily identifiable fr...
Preprint
Full-text available
The expanding field of epitranscriptomics might rival the epigenome in the diversity of the biological processes impacted. However, the identification of modifications in individual RNA molecules remains challenging. We present CHEUI, a new method that detects N6-methyladenosine (m6A) and 5-methylcytidine (m5C) at single-nucleotide and single-molec...
Preprint
Full-text available
Relapse remains a major challenge in the clinical management of acute myeloid leukemia (AML), and is driven by rare therapy-resistant leukemia-initiating stem cells (LSCs) that reside in specific bone marrow niches. Hypoxia signaling keeps cells in a quiescent and metabolically relaxed state, desensitizing them to chemotherapy. This suggests the hy...
Article
Full-text available
The high-throughput sequencing of cellular RNAs has underscored a broad effect of isoform diversification through alternative splicing on the transcriptome. Moreover, the differential production of transcript isoforms from gene loci has been recognized as a critical mechanism in cell differentiation, organismal development, and disease. Yet, the ex...
Preprint
Full-text available
A significant proportion of B-cell acute lymphoblastic leukemia (B-ALL) patients remains with a dismal prognosis due to yet undetermined mechanisms. We performed a comprehensive multicohort analysis of gene fusions, gene expression, and RNA splicing alterations to uncover molecular signatures potentially linked to the observed poor outcome. We iden...
Preprint
Full-text available
A significant proportion of B-cell acute lymphoblastic leukemia (B-ALL) patients remains with a dismal prognosis due to yet undetermined mechanisms. We performed a comprehensive multicohort analysis of gene fusions, gene expression, and RNA splicing alterations to uncover molecular signatures potentially linked to the observed poor outcome. We iden...
Article
Purpose Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy). Methods A total of 74...
Article
Full-text available
Immunotherapies provide effective treatments for previously untreatable tumors and identifying tumor-specific epitopes can help elucidate the molecular determinants of therapy response. Here, we describe a pipeline, ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer), for the comprehensive identification of tumor-specific splicing-derived epi...
Article
Germline pathogenic variants in BRCA1 confer a high risk of developing breast and ovarian cancer. The BRCA1 exon 11 (formally exon 10) is one of the largest exons and codes for the nuclear localization signals of the corresponding gene product. This exon can be partially or entirely skipped during pre-mRNA splicing, leading to three major in-frame...
Preprint
Full-text available
Williams-Beuren syndrome (WBS) is a rare genetic multisystemic disorder characterized by mild to moderate intellectual disability and hypersocial phenotype, while the most life-threatening features are cardiovascular abnormalities. Nowadays, there are no available treatments to ameliorate the main traits of WBS. The endocannabinoid system (ECS), gi...
Article
Full-text available
DNA methylation plays a fundamental role in the control of gene expression and genome integrity. Although there are multiple tools that enable its detection from Nanopore sequencing, their accuracy remains largely unknown. Here, we present a systematic benchmarking of tools for the detection of CpG methylation from Nanopore sequencing using individ...
Article
Full-text available
Viral co-infections occur in COVID-19 patients, potentially impacting disease progression and severity. However, there is currently no dedicated method to identify viral co-infections in patient RNA-seq data. We developed PACIFIC, a deep-learning algorithm that accurately detects SARS-CoV-2 and other common RNA respiratory viruses from RNA-seq data...
Preprint
Full-text available
PAX5 is the master transcription factor controlling B cell identity. In humans, mutations in PAX5 account for 30% of B cell acute lymphoblastic leukemia (B-ALL) cases. Investigating the causal effects of PAX5 mutations has however been difficult due to the premature lethality of Pax5 −/− mice. Here we describe a novel mouse strain with a premature...
Article
Transition through cell cycle phases requires temporal and spatial regulation of gene expression to ensure accurate chromosome duplication and segregation. This regulation involves dynamic reprogramming of gene expression at multiple transcriptional and posttranscriptional levels. In transcriptionally silent oocytes, the CPEB-family of RNAbinding p...
Preprint
Full-text available
DNA methylation plays a fundamental role in the control of gene expression and genome integrity. Although there are multiple tools that enable its detection from Nanopore sequencing, their accuracy remains largely unknown. Here, we present a systematic benchmarking of tools for the detection of CpG methylation from Nanopore sequencing using individ...
Preprint
Full-text available
Viral co-infections occur in COVID-19 patients, potentially impacting disease progression and severity. However, there is currently no dedicated method to identify viral co-infections in patient RNA-seq data. We developed PACIFIC, a deep-learning algorithm that accurately detects SARS-CoV-2 and other common RNA respiratory viruses from RNA-seq data...
Preprint
Full-text available
Immunotherapies provide effective treatments for previously untreatable tumors and identifying tumor-specific epitopes can help elucidate the molecular determinants of therapy response. Here, we describe a pipeline, ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer), for the comprehensive identification of tumor-specific splicing-derived epi...
Article
Full-text available
The differential production of transcript isoforms from gene loci is a key cellular mechanism. Yet, its impact in protein production remains an open question. Here, we describe ORQAS (ORF quantification pipeline for alternative splicing), a pipeline for the translation quantification of individual transcript isoforms using ribosome-protected mRNA f...
Preprint
Full-text available
Single-molecule long-read sequencing provides an unprecedented opportunity to measure the transcriptome from any sample 1–3 . However, current methods for the analysis of transcriptomes from long reads rely on the comparison with a genome or transcriptome reference 2,4,5 , or use multiple sequencing technologies 6,7 . These approaches preclude the...
Article
Full-text available
Abstract We describe ReorientExpress, a method to perform reference-free orientation of transcriptomic long sequencing reads. ReorientExpress uses deep learning to correctly predict the orientation of the majority of reads, and in particular when trained on a closely related species or in combination with read clustering. ReorientExpress enables lo...
Preprint
Full-text available
The differential production of transcript isoforms from gene loci is a key mechanism in multiple biological processes and pathologies. Although this has been exhaustively shown at RNA level, it remains elusive at protein level. Here, we describe a new pipeline ORQAS (ORF quantification pipeline for alternative splicing) for the translation quantifi...
Preprint
Full-text available
Long-read sequencing technologies allow the systematic interrogation of transcriptomes from any species. However, functional characterization requires the determination of the correct orientation of reads. Oxford Nanopore Technologies (ONT) allows the direct measurement of RNA molecules in the native orientation, but sequencing of complementary-DNA...
Article
Full-text available
The authors would like to correct the inadvertent omission of a funding source in the Acknowledgments section of the initial publication of this article. The corrected text is as follows and has been updated online:
Article
Current annotation methods typically classify mutations as disruptors of splicing if they fall on either the consensus intronic dinucleotide splice donor, GT, or the splice acceptor, AG. As a group, splice site mutations have been presumed to be invariably deleterious because of their disruption of the conserved sequences that are used to identify...
Article
For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for the large-scale discovery of splice-site-creating mutations (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated mutati...
Article
Full-text available
RNA-protein binding is critical to gene regulation, controlling fundamental processes including splicing, translation, localization and stability, and aberrant RNA-protein interactions are known to play a role in a wide variety of diseases. However, molecular understanding of RNA-protein interactions remains limited; in particular, identification o...
Data
Four different classes of designed sequences used for the RNA Bind-N-Seq validations for SLBP. (DOCX)
Data
Comparison of RBP motifs found per graph transformation option and DBSCAN threshold. (DOCX)
Data
Best k-mer found for all RBPs considered. For each RBP, the z-score is given for the k-mer with the maximal value of Z-score*k. (DOCX)
Data
DEseq2 results for all sequences generated to test SLBP candidate motifs. (XLSX)
Data
Sequence logo and structural context found by RNAcontext on ILF3. (DOCX)
Data
All motif and random sequences generated for benchmarking SARNAclust. (XLSX)
Data
Clustering quality measures for each (Adjusted Rand Index (ARI), Adjusted Mutual Information (AMI), Homogeneity Score (HS), Completeness Score (CS), V-measure score (VMS) and Fowlkes-Mallows score (FMS)) for all thresholds and options as described in the benchmarking section. (XLSX)
Data
Four different classes of designed sequences used for the RNA Bind-N-Seq validations for ILF3. (DOCX)
Data
DEseq2 results for all sequences generated to test ILF3 candidate motifs. (XLSX)
Data
Pipeline for CLIP peak detection. Given bam files for samples and control, pyicoclip is used to detect significant peaks in each file. Afterwards, we filter those peaks that do not appear in all the samples and remove those that can be found in the control. The resulting peaks are annotated and the sequences for them (+/- 100 flanking nucleotides)...
Data
Graphical representation of all the graph transformation options. SF2.k corresponds to graph transformation option k as explained in the main text. Examples are shown for sequence/structure: GGGGAAACCAACCUGU ((((. . .))..)) . . . (DOCX)
Data
Sequence logo and structural context found by RNAcontext on the synthetic dataset. (DOCX)
Data
SDS-PAGE gel showing the result of GST affinity purification of GST-SBP, GST-SBP-SLBP and GST-SBP-ILF3. Proteins of this purity were used in RBNS and gel shift assays. (DOCX)
Data
Logo for SLBP consensus motif sequences that a) show enriched binding and b) do not show enriched binding. (DOCX)
Article
A major challenge in cancer research is to determine the biological and clinical significance of somatic mutations in noncoding regions. This has been studied in terms of recurrence, functional impact, and association to individual regulatory sites, but the combinatorial contribution of mutations to common RNA regulatory motifs has not been explore...
Article
Full-text available
Despite the many approaches to study differential splicing from RNA-seq, many challenges remain unsolved, including computing capacity and sequencing depth requirements. Here we present SUPPA2, a new method that addresses these challenges, and enables streamlined analysis across multiple conditions taking into account biological variability. Using...
Preprint
Full-text available
A major challenge in cancer research is to determine the biological and clinical significance of somatic mutations in non-coding regions. This has been studied in terms of recurrence, functional impact, and association to individual regulatory sites, but the combinatorial contribution of mutations to common RNA regulatory motifs has not been explor...
Article
Full-text available
Melanomas are well-known for their altered mRNA expression profiles. Yet, the specific contribution of mRNA binding proteins (mRBPs) to melanoma development remains unclear. Here we identify a cluster of melanoma-enriched genes under the control of CUGBP Elav-like family member 1 (CELF1). CELF1 was discovered with a distinct prognostic value in mel...