Browsing ICR Divisions by author "Zapata Ortiz, Luis"
Now showing items 1-17 of 17
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Allele balance bias identifies systematic genotyping errors and false disease associations.
Muyas, F; Bosio, M; Puig, A; Susak, H; Domènech, L; et al. (WILEY, 2019-01-01)In recent years, next-generation sequencing (NGS) has become a cornerstone of clinical genetics and diagnostics. Many clinical applications require high precision, especially if rare events such as somatic mutations in ... -
Chromosome-level assembly of Arabidopsis thaliana Ler reveals the extent of translocation and inversion polymorphisms.
Zapata, L; Ding, J; Willing, E-M; Hartwig, B; Bezdan, D; et al. (NATL ACAD SCIENCES, 2016-07-12)Resequencing or reference-based assemblies reveal large parts of the small-scale sequence variation. However, they typically fail to separate such local variation into colinear and rearranged variation, because they usually ... -
Evolutionary dynamics of neoantigens in growing tumors.
Lakatos, E; Williams, MJ; Schenck, RO; Cross, WCH; Househam, J; et al. (NATURE PORTFOLIO, 2020-10-01)Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of ... -
Geospatial immune variability illuminates differential evolution of lung adenocarcinoma.
AbdulJabbar, K; Raza, SEA; Rosenthal, R; Jamal-Hanjani, M; Veeriah, S; et al. (NATURE PORTFOLIO, 2020-07-01)Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1-5. However, the spatial configurations of immune and stromal cells, which may shed light on ... -
Immune selection determines tumor antigenicity and influences response to checkpoint inhibitors.
Zapata, L; Caravagna, G; Williams, MJ; Lakatos, E; AbdulJabbar, K; et al. (NATURE PORTFOLIO, 2023-03-01)In cancer, evolutionary forces select for clones that evade the immune system. Here we analyzed >10,000 primary tumors and 356 immune-checkpoint-treated metastases using immune dN/dS, the ratio of nonsynonymous to synonymous ... -
Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.
Cresswell, GD; Nichol, D; Spiteri, I; Tari, H; Zapata, L; et al. (NATURE PORTFOLIO, 2020-03-27)Circulating tumour DNA (ctDNA) allows tracking of the evolution of human cancers at high resolution, overcoming many limitations of tissue biopsies. However, exploiting ctDNA to determine how a patient's cancer is evolving ... -
Measuring the distribution of fitness effects in somatic evolution by combining clonal dynamics with dN/dS ratios.
Williams, MJ; Zapata, L; Werner, B; Barnes, CP; Sottoriva, A; et al. (ELIFE SCIENCES PUBLICATIONS LTD, 2020-03-30)The distribution of fitness effects (DFE) defines how new mutations spread through an evolving population. The ratio of non-synonymous to synonymous mutations (dN/dS) has become a popular method to detect selection in ... -
Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.
Zapata, L; Pich, O; Serrano, L; Kondrashov, FA; Ossowski, S; et al. (BMC, 2018-05-31)BACKGROUND: Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic ... -
Nuclear gene proximity and protein interactions shape transcript covariations in mammalian single cells.
Tarbier, M; Mackowiak, SD; Frade, J; Catuara-Solarz, S; Biryukova, I; et al. (NATURE RESEARCH, 2020-10-28)Single-cell RNA sequencing studies on gene co-expression patterns could yield important regulatory and functional insights, but have so far been limited by the confounding effects of differentiation and cell cycle. We apply ... -
Phenotypic plasticity and genetic control in colorectal cancer evolution.
Househam, J; Heide, T; Cresswell, GD; Spiteri, I; Kimberley, C; et al. (NATURE PORTFOLIO, 2022-11-24)Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity1. The interplay of these biological processes and their respective contributions to tumour evolution remain ... -
Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes.
Loupakis, F; Depetris, I; Biason, P; Intini, R; Prete, AA; et al. (WILEY, 2020-01-22)BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); however, specific predictive biomarkers are lacking. ... -
The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues.
Muyas, F; Zapata, L; Guigó, R; Ossowski, S (BMC, 2020-05-27)BACKGROUND: Mosaic mutations acquired during early embryogenesis can lead to severe early-onset genetic disorders and cancer predisposition, but are often undetectable in blood samples. The rate and mutational spectrum of ... -
Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genes.
Zapata, L; Susak, H; Drechsel, O; Friedländer, MR; Estivill, X; et al. (NATURE PORTFOLIO, 2017-10-13)Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell ... -
Single-cell genetic analysis of clonal dynamics in colorectal adenomas indicates CDX2 gain as a predictor of recurrence.
Fiedler, D; Heselmeyer-Haddad, K; Hirsch, D; Hernandez, LS; Torres, I; et al. (WILEY, 2019-04-01)Colorectal adenomas are common precancerous lesions with the potential for malignant transformation to colorectal adenocarcinoma. Endoscopic polypectomy provides an opportunity for cancer prevention; however, recurrence ... -
Subclonal reconstruction of tumors by using machine learning and population genetics.
Caravagna, G; Heide, T; Williams, MJ; Zapata, L; Nichol, D; et al. (NATURE PUBLISHING GROUP, 2020-09-01)Most cancer genomic data are generated from bulk samples composed of mixtures of cancer subpopulations, as well as normal cells. Subclonal reconstruction methods based on machine learning aim to separate those subpopulations ... -
The co-evolution of the genome and epigenome in colorectal cancer.
Heide, T; Househam, J; Cresswell, GD; Spiteri, I; Lynn, C; et al. (NATURE PORTFOLIO, 2022-11-24)Colorectal malignancies are a leading cause of cancer-related death1 and have undergone extensive genomic study2,3. However, DNA mutations alone do not fully explain malignant transformation4-7. Here we investigate the ... -
Very large hidden genetic diversity in one single tumor: evidence for tumors-in-tumor.
Chen, B; Wu, X; Ruan, Y; Zhang, Y; Cai, Q; et al. (OXFORD UNIV PRESS, 2022-12-12)Despite the concern of within-tumor genetic diversity, this diversity is in fact limited by the kinship among cells in the tumor. Indeed, genomic studies have amply supported the 'Nowell dogma' whereby cells of the same ...