Author
Diego Miranda-Saavedra
Other affiliations: University of Oxford, Genome Institute of Singapore, Wellcome Trust ...read more
Bio: Diego Miranda-Saavedra is an academic researcher from Spanish National Research Council. The author has contributed to research in topics: Genome & Protein tyrosine phosphatase. The author has an hindex of 38, co-authored 59 publications receiving 7559 citations. Previous affiliations of Diego Miranda-Saavedra include University of Oxford & Genome Institute of Singapore.
Papers
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Broad Institute1, University of Amsterdam2, University of California, Riverside3, University of Arizona4, Université Paris-Saclay5, University of Córdoba (Spain)6, Oregon State University7, Aix-Marseille University8, Pennsylvania State University9, Texas A&M University10, Purdue University11, University of California, Irvine12, Rothamsted Research13, Pacific Northwest National Laboratory14, University of Minnesota15, United States Department of Agriculture16, Centre national de la recherche scientifique17, University of Texas Southwestern Medical Center18, University of California, Los Angeles19, Commonwealth Scientific and Industrial Research Organisation20, Seoul National University21, University of Texas at Dallas22, University of Cambridge23, University of Wisconsin-Madison24, Cornell University25
TL;DR: Comparison of genomes of three phenotypically diverse Fusarium species revealed lineage-specific genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome, putting the evolution of fungal pathogenicity into a new perspective.
Abstract: Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
1,386 citations
J. Craig Venter Institute1, Alfred Wegener Institute for Polar and Marine Research2, École Normale Supérieure3, San Diego State University4, Fraunhofer Society5, Charles University in Prague6, Scottish Association for Marine Science7, Kobe University8, University of Mainz9, University of Arizona10, University of Tennessee Health Science Center11, California State University, Los Angeles12
TL;DR: The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further.
Abstract: Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further
809 citations
Newcastle University1, J. Craig Venter Institute2, University of Maryland, College Park3, University of Glasgow4, Technical University of Denmark5, University of Calgary6, Natural History Museum7, Ghent University8, University of Dundee9, University of Sassari10, University of California, Los Angeles11, Children's Hospital Oakland Research Institute12, Charles University in Prague13, University of Iowa14, University of Düsseldorf15, University of California, San Francisco16, University of Queensland17, QIMR Berghofer Medical Research Institute18, Chang Gung University19, University of Strathclyde20
TL;DR: The genome sequence of the protist Trichomonas vaginalis predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
Abstract: We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the similar to 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
751 citations
J. Craig Venter Institute1, University of Pittsburgh2, Imperial College London3, University of Dundee4, New England Biolabs5, University of Edinburgh6, Lyon College7, Australian National University8, University of Toledo9, University of California, Davis10, Smith College11, Washington University in St. Louis12, New York Blood Center13, National Institutes of Health14, University of Göttingen15, University of Alabama at Birmingham16, Johns Hopkins University17
TL;DR: In this article, the authors sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predicted ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence.
Abstract: Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.
583 citations
TL;DR: Evidence that the pseudokinase STRAD controls the function of the tumour suppressor kinase LKB1 is reviewed and that a single amino acid substitution within the pseudokerase domain of the tyrosine kinase JAK2 leads to several malignant myeloproliferative disorders.
523 citations
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: CIBERSORT outperformed other methods with respect to noise, unknown mixture content and closely related cell types when applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen and fixed tissues, including solid tumors.
Abstract: We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content and closely related cell types CIBERSORT should enable large-scale analysis of RNA mixtures for cellular biomarkers and therapeutic targets (http://cibersortstanfordedu/)
6,967 citations
North Carolina State University1, Wageningen University and Research Centre2, University of the Free State3, Rothamsted Research4, University of Córdoba (Spain)5, Imperial College London6, Texas A&M University7, Max Planck Society8, Commonwealth Scientific and Industrial Research Organisation9, University of Bristol10
TL;DR: A short resumé of each fungus in the Top 10 list and its importance is presented, with the intent of initiating discussion and debate amongst the plant mycology community, as well as laying down a bench-mark.
Abstract: The aim of this review was to survey all fungal pathologists with an association with the journal Molecular Plant Pathology and ask them to nominate which fungal pathogens they would place in a 'Top 10' based on scientific/economic importance. The survey generated 495 votes from the international community, and resulted in the generation of a Top 10 fungal plant pathogen list for Molecular Plant Pathology. The Top 10 list includes, in rank order, (1) Magnaporthe oryzae; (2) Botrytis cinerea; (3) Puccinia spp.; (4) Fusarium graminearum; (5) Fusarium oxysporum; (6) Blumeria graminis; (7) Mycosphaerella graminicola; (8) Colletotrichum spp.; (9) Ustilago maydis; (10) Melampsora lini, with honourable mentions for fungi just missing out on the Top 10, including Phakopsora pachyrhizi and Rhizoctonia solani. This article presents a short resume of each fungus in the Top 10 list and its importance, with the intent of initiating discussion and debate amongst the plant mycology community, as well as laying down a bench-mark. It will be interesting to see in future years how perceptions change and what fungi will comprise any future Top 10.
2,807 citations
TL;DR: The biochemical, structural and genetic studies that have clarified how the interplay between members of the BCL-2 family on mitochondria sets the apoptotic threshold are discussed, illuminating the physiological control of apoptosis, the pathological consequences of its dysregulation and the promising search for novel cancer therapies that target the BCA2 protein family.
Abstract: The BCL-2 protein family determines the commitment of cells to apoptosis, an ancient cell suicide programme that is essential for development, tissue homeostasis and immunity. Too little apoptosis can promote cancer and autoimmune diseases; too much apoptosis can augment ischaemic conditions and drive neurodegeneration. We discuss the biochemical, structural and genetic studies that have clarified how the interplay between members of the BCL-2 family on mitochondria sets the apoptotic threshold. These mechanistic insights into the functions of the BCL-2 family are illuminating the physiological control of apoptosis, the pathological consequences of its dysregulation and the promising search for novel cancer therapies that target the BCL-2 family.
2,446 citations
Journal Article•
TL;DR: FastTree as mentioned in this paper uses sequence profiles of internal nodes in the tree to implement neighbor-joining and uses heuristics to quickly identify candidate joins, then uses nearest-neighbor interchanges to reduce the length of the tree.
Abstract: Gene families are growing rapidly, but standard methods for inferring phylogenies do not scale to alignments with over 10,000 sequences. We present FastTree, a method for constructing large phylogenies and for estimating their reliability. Instead of storing a distance matrix, FastTree stores sequence profiles of internal nodes in the tree. FastTree uses these profiles to implement neighbor-joining and uses heuristics to quickly identify candidate joins. FastTree then uses nearest-neighbor interchanges to reduce the length of the tree. For an alignment with N sequences, L sites, and a different characters, a distance matrix requires O(N^2) space and O(N^2 L) time, but FastTree requires just O( NLa + N sqrt(N) ) memory and O( N sqrt(N) log(N) L a ) time. To estimate the tree's reliability, FastTree uses local bootstrapping, which gives another 100-fold speedup over a distance matrix. For example, FastTree computed a tree and support values for 158,022 distinct 16S ribosomal RNAs in 17 hours and 2.4 gigabytes of memory. Just computing pairwise Jukes-Cantor distances and storing them, without inferring a tree or bootstrapping, would require 17 hours and 50 gigabytes of memory. In simulations, FastTree was slightly more accurate than neighbor joining, BIONJ, or FastME; on genuine alignments, FastTree's topologies had higher likelihoods. FastTree is available at http://microbesonline.org/fasttree.
2,436 citations