Irene Lobón
A5004606329- Cancer Genomics and Diagnostics
- Renal cell carcinoma treatment
- Melanoma and MAPK Pathways
- Cutaneous Melanoma Detection and Management
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Computational Drug Discovery Methods
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Cell Image Analysis Techniques
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Primate Behavior and Ecology
- Immune Cell Function and Interaction
- Yersinia bacterium, plague, ectoparasites research
- Pleistocene-Era Hominins and Archaeology
- Prostate Cancer Treatment and Research
- Chemical Reactions and Isotopes
- Renal and related cancers
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Bat Biology and Ecology Studies
The Francis Crick Institute
2022-2025
Universitat Pompeu Fabra
2015-2024
Institut de Biologia Evolutiva
2015-2023
Universitat de Barcelona
2020
Departament de Salut
2016
Barcelona Biomedical Research Park
2015
Genomes in the mist The mountain gorilla is an iconic species that at high risk of extinction. Xue et al. have sequenced 13 gorillas from two different populations to probe their genetic diversity. genomes show large tracts homozygosity and loss highly deleterious variants, indicating population bottlenecks inbreeding. This diversity appears started over 20,000 years ago may been caused by changes climate human-associated effects. Science , this issue p. 242
The spread of farming out the Balkans and into rest Europe followed two distinct routes: An initial expansion represented by Impressa Cardial traditions, which Northern Mediterranean coastline; another LBK (Linearbandkeramik) tradition, Danube River Central Europe. Although genomic data now exist from samples representing second migration, such have yet to be successfully generated migration. To address this, we complete genome a 7,400-year-old individual (CB13) Cova Bonica in Vallirana...
We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 schizophrenia, and 59 autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, had 20 60 detectable single-nucleotide mutations, but ~6% harbored hundreds mutations. Hypermutability was associated age damaging in genes implicated cancers and, some brains, reflected vivo clonal expansions. Somatic duplications, likely arising during development, were found ~5% normal...
Abstract Understanding the evolutionary pathways to metastasis and resistance immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present most comprehensive intrapatient metastatic dataset assembled date as part of Posthumous Evaluation Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed...
Abstract Although the key aspects of genetic evolution and their clinical implications in clear-cell renal cell carcinoma (ccRCC) are well documented, how features coevolve with phenotype tumor microenvironment (TME) remains elusive. Here, through joint genomic–transcriptomic analysis 243 samples from 79 patients recruited to TRACERx Renal study, we identify pervasive nongenetic intratumor heterogeneity, over 40% not attributable alterations. By integrating transcriptomes phylogenetic...
Abstract Background Post-zygotic mutations incurred during DNA replication, repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in from non-cancerous tissues poses significant challenges, particularly if the only are present a small fraction cells. Results Here, Brain Mosaicism Network conducts coordinated, multi-institutional study examine ability existing methods...
Abstract Archaic admixture has had a substantial impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. In great apes, archaic been identified in chimpanzees bonobos but the possibility of not explored other species. Here, we address this question using high-coverage whole-genome sequences all four extant gorilla subspecies, six newly sequenced eastern gorillas previously unsampled...
Abstract When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant that evade surveillance can lead to cancer. Neurons with karyotypes arise during neurotypical brain development, but neurons almost never origin of cancers. Instead, mutations in bring about neurodevelopmental disorders, and contribute polygenic landscape neuropsychiatric neurodegenerative disease. A subset human harbors idiosyncratic copy number variants (CNVs, “CNV neurons”),...
Changes in the epigenetic regulation of gene expression have a central role evolution. Here, we extensively profiled panel human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq RNA-seq, further complemented with whole genome sequencing (WGS) bisulfite (WGBS). We annotated regulatory elements (RE) integrated chromatin contact maps to define architectures, creating largest catalog RE primates date. report that...
<p>Heterogeneity of the TME in ccRCC. <b>A,</b> Association cell abundance estimates from consensus and evolutionary trajectory tumor which sample is taken (in 171 primary samples). Comparisons are one against all using a linear mixed-effects model to control for inclusion multiple samples same patient. <i>P</i>-values corrected hypothesis testing by Benjamini–Hochberg (FDR). Significant associations (FDR < 0.05) highlighted with thicker borders. Negative...
<p>Evaluation of the potential to reconstruct TCR repertiore from bulk RNA-Sequencing data</p>
<p>Transcriptional evolution mirrors clonal structure and follows recurrent trends. <b>A,</b> Transcriptional distance between primary tumor samples other or adjacent normal kidney (12 patients with both available primary–primary primary–normal pairs). <b>B,</b> Proportion of genes significantly associated changes in expression normal–primary pairs using a gene-specific linear regression framework (see “Methods”). <b>C,</b> matched metastases (seven...
<p>Greater overall HERV expression, strongly associated with VHL loss of function, correlates longer progression-free survival in ccRCC. <b>A</b>, Distribution TRACERx Renal (<i>n</i> = 243 samples) the median expression across 615 transcripts overlapping annotated retroelements (HERVs and LTRs) by sample genotype. Boxes extend from lower to upper quartiles, line inside box representing median, whiskers indicating data within 1.5 times IQR quartiles....
<p>All Supplementary Figures are provided in PDF format with the corresponding legend after each figure. Figure 1. Genetic and clinical composition of TRACERx Renal cohort 2. Comparison between transcriptional inter intratumour heterogeneity 3. Representation I-TED to measure robustness analysis 4. Transcriptional ITH is not associated poorer outcomes ccRCC 5. Subclonal 9p loss subclonal somatic copy-number alteration greatest association 6. Variance explained by major clinico-genomic...
<p>Transcriptional inter- and intratumor heterogeneity is pervasive in TRACERx Renal. <b>A,</b> UMAP visualizing the transcriptional variation across 231 tumor samples (gray points). Samples from patients K390, K243, K153 are highlighted to illustrate varied levels of ITH distinct patients. For patient K153, we highlight phylogenetic tree branch containing clones observed adjacent sample points. <b>B,</b> Schematic representation calculation distance between two...
<div>Abstract<p>Although the key aspects of genetic evolution and their clinical implications in clear-cell renal cell carcinoma (ccRCC) are well documented, how features coevolve with phenotype tumor microenvironment (TME) remains elusive. Here, through joint genomic–transcriptomic analysis 243 samples from 79 patients recruited to TRACERx Renal study, we identify pervasive nongenetic intratumor heterogeneity, over 40% not attributable alterations. By integrating transcriptomes...