Mostrando entradas con la etiqueta filogenómica. Mostrar todas las entradas
Mostrando entradas con la etiqueta filogenómica. Mostrar todas las entradas

28 de abril de 2022

Gabriela y la dinámica molecular

Hola,

esta mañana leía sobre el descubrimiento de que una mutación en el gen TLR7 es suficiente para causar lupus eritematoso sistémico (LES), una enfermedad autoinmune. La mutación es la sustitución Y264H, deletérea según los programas SIFT y CADD (ver otras opciones aquí), de la que es portadora Gabriela, una chica madrileña. 

El artículo completo está en https://doi.org/10.1038/s41586-022-04642-z , yo quería simplemente destacar parte de la primera figura:

Adaptada del original en https://doi.org/10.1038/s41586-022-04642-z

En el alineamiento múltiple de arriba se puede ver que la tirosina Y264 está muy conservada en animales, y por eso SIFT le asigna una puntuación de 0.12 al cambio por histidina (otras dos mutaciones no sinónimas tienen puntuaciones de 0.05 y 0). 

El panel del medio muestra la unión del ligando guanosina al receptor silvestre TLR7 (Y264) y el de abajo con el receptor mutado, donde se ve que se libera volumen que ocupan varias moléculas de agua, aumentando a la vez la afinidad por la guanosina.

Este análisis fue posible por la disponibilidad de tres estructuras de la proteína ortóloga en Maccaca mulata en el PDB (6IF55GMF y 5GMH), que fueron usadas como punto de partida para hacer varias simulaciones de dinámica molecular que se describen con detalle (3 páginas) en el material suplementario,

hasta pronto,

Bruno

15 de octubre de 2020

Plant Genomes in a Changing environment 2020

Hi, this year's Plant Genomes in a Changing Environment was virtual with hashtag #PlantGenomes20.  Check the full program here. I post here my notes on the talks I was able to attend, either live or on the recorded videos, in case they're useful for anyone out there.

Giles Oldroyd (Sainbury lab, UK) talked about a pathway conserved in plants forming intracellular endosymbiotic mycorrhizaephytes. The pathway is not found in species forming exclusively extracellular symbioses, such as ectomycorrhizae, and those forming associations with cyanobacteria. This is described at https://www.nature.com/articles/s41477-020-0613-7. Receptors used with potential symbionts are the same used to recognize chitin and peptide-glicans of pathogens. Symbiotic potential decreases when there's enough nutriends at hand.

 

Figure from https://www.biorxiv.org/content/10.1101/804591v1.full

 

N Marmiroli (SITEIA.PARMA, Italy) presented a poster about the https://simbaproject.eu, where they are testing in plots in Italy and Germany the application of Plant Growth-Promoting Microbes to wheat, maize, tomato and potato under abiotic stress conditions.

Trevor Nolan (Duke U, USA) talked about their efforts in harmonizing single cell mRNA sequencing data from 110K cells to construct an atlas for the developing Arabidopsis thaliana root. Read more at https://www.biorxiv.org/content/10.1101/2020.06.29.178863v1


Francesco Licausi (Oxford U, UK) described the strategies of flooding tolerance in plants, which can be used to breed flooding varieties of crops. Flooding is a composite stress, he focus on two components: oxygen sensing and responses to oxidative stress, which are mediated among others by NAC transcription factors such as ANAC017, read more at https://onlinelibrary.wiley.com/doi/full/10.1111/pce.13037 and https://onlinelibrary.wiley.com/doi/abs/10.1111/tpj.14975


 Ana Caño Delgado (CRAG, Spain)
delivered a lecture on physiology and molecular biology of Arabidopsis plants and their responses to drought mediated by brassinosteroids receptors in the root tip. Among many experiments, they measure response to drought as function of root branching angles. Read more at https://www.nature.com/articles/s41467-018-06861-3 and https://science.sciencemag.org/content/368/6488/266.abstract

Steve Long (Lancaster U, UK) shared his knowledge on breeding for incresing photosynthesis efficienty. This figure is from a 2010 review https://www.annualreviews.org/doi/10.1146/annurev-arplant-042809-112206, but still quite impressive:



Alexander Borowsky (U California, Riverside, USA) uses their own coexpression network pipeline (Wisecaver 2019) and the Taiji pipeline to analyze their ATACseq data in order to find key transcription factors regulating responses to water logging and water deficit in rice. They plan to do validation work using CRISPR to confirm their results.

Julia Bailey-Serres (U California, Riverside, USA) gave a keynote with two parts. While the second was related to A Borowsky0s talk, on the first part, she and her team looked at the transcriptional regulation of responses to submergence/flooding by comparing 4 different species (rice, Medicago truncatula, domesticated tomato and its dryland-adapted wild relative Solanum pennellii). By combining RNA-seq and ATACseq data and different computational analyses they found 68 Submerged Upregulated oRthologous Families (SURFs) upregulated in both monocots and dicots, with hypoxia-responsive promoter element (HRPE) motifs being abundant in rice but scarce in promoters of SURFs in dryland-adapted S. pennellii. This piece of work is described at https://science.sciencemag.org/content/365/6459/1291

Figure from https://science.sciencemag.org/content/365/6459/1291

They have really nive figure, shown below, where DNA motifs instead of transcription factors are the vertices of the graph. Despite the differences observed in the network across species, 4 motifs seem to be highly conserved:

Figure from https://science.sciencemag.org/content/365/6459/1291

 

Klaas Vandepoele (VIB-Ugent Center for Plant Systems Biology, Belgium) and his team have been doing a conceptually similar analysis, with RNA-seq from A. thaliana, Populus trichocarpa and maize, in order to identify gene triplets with conserved leaf expression pattern which are conserved across monocots and dicots. They validate their results by phenotyping A. thaliana mutants in the glass house.  Their work has been published at https://onlinelibrary.wiley.com/doi/full/10.1111/pbi.13223. He also mentions this paper https://pubmed.ncbi.nlm.nih.gov/31748815 which describes modules of genes involved in cell proliferation in the leaf.

Jeff Habben (Corteva, USA) describes their extensive field trials in low and high-yielding locations, mostly across the US, to check whether different transgenic lines that overexpress maize transcription factor zmm28 (MADS-box) have higher and more stable yields. Their work is described in detail at https://www.pnas.org/content/116/47/23850

Facundo Romani (CONICET, Argentina) explains how liverwort Marchantia polymorpha defends itself against hervibores by accumulating terpenes in oil bodies, a process controlled by HD-ZIP transcription factor MpC1HDZ. This work is described at https://www.sciencedirect.com/science/article/abs/pii/S0960982220307685

Sandra Knapp (Natural History Museum-London, UK) , a plant taxonomist, talks about diversity of Solanaceae (nightshades), starting with potatoes

Source: Sandra Knapp

She discusses how we usually think of aridification as something bad but according tho their work in Australia (https://onlinelibrary.wiley.com/doi/full/10.1111/jse.12638) it seems to be certainly a driver of diversification. She suggests we should be looking at plant lineages that have this pattern to prepare for climate change. One possible way would be to learn from resistant weeds in order to create resistant crops (https://www.sciencedirect.com/science/article/abs/pii/S0304423818307994). This is aligned with the work of Dana MacGregor, which also had a talk in this session.

She terminates by acknowledging the collective effort of people studying nightshades around the world (http://solanaceaesource.org) and a warning about the excess of P/N consum by agriculture and the current rates of extinction, that cause an unsustainable loss of diversity.

Michael Purugganan (New York University, USA) talks about the domestication of rice (which tokk 4K years) and molecular studies to understand the geographic spread of primarily japonica rice in Asia. His two main figures are:

 Figure from https://pubmed.ncbi.nlm.nih.gov/28087768/


 

Tal Dahan Meir (Weizmann Institute of Science, Israel) spoke about a long term observation seris of a wild Emmer wheat population in Isreal. Unfortunately I could not see the most relevant slides in the saved video, but het talk reminded me of the Eviatar Nevo's talk last year at the Brachypodium conference (see https://www.youtube.com/watch?v=UhNzH39zLbk).

Guy Naamati (Ensembl Plants, EMBL-EBI, UK) presented a poster about the wheat Pan Genome and status at Ensembl Plant. The programmatic access recipes mentioned in the poster can be found at https://github.com/Ensembl/plant_tools/tree/master/demo_scripts

Click on the image to download and see full size

4 de julio de 2017

rooting and laddering Newick trees

Buenas,
esta entrada es para compartir un script Perl para enraizar árboles, muchos árboles, de manera automática, y ordenar los nodos por distancia. Pongo el título en inglés para los buscadores.
Rubén Sancho y yo estamos probando el software GRAMPA, que requiere una colección de árboles de genes precalculados en formato Newick, pero además los quiere enraizados y ordenados de manera ascendente. Como son más de mil árboles no lo queríamos hacer uno a uno con FigTree, por poner un ejemplo; queríamos automatizarlo y para ello aprovechamos los módulos Bio::TreeIO y Bio::Phylo. El primero es de Bioperl y ya lo tenía instalado, el segundo lo instalé con: $ sudo cpanm Bio::Phylo

El árbol de ejemplo, contenido en el fichero unrooted.ph, es:

(1_Sbic:0.047,2_Osat:0.068,(((((((((((3_B422:0.007,(((4_Barb:0.000,((5_Bret:0.003,(6_BsyE:0.000,7_BsyE:0.000):0.000):0.000,8_BsyC:0.000):0.000):0.000,9_Bpho:0.002):0.000,(10_BsyC:0.000,11_BsyC:0.000):0.001):0.000):0.008,((12_B422:0.005,13_Bpho:0.005):0.002,14_Barb:0.000):0.005):0.000,((((15_Bdis:0.000,16_Bdis:0.000):0.000,17_Bmex:0.033):0.013,18_Bhyb:0.001):0.014,(19_Bboi:0.021,((20_Bmex:0.017,21_Bsta:0.034):0.012,22_Bsta:0.000):0.003):0.020):0.012):0.002,23_Barb:0.000):0.000,24_Brup:0.012):0.000,25_BsyG:0.000):0.000,(26_Bpin:0.000,27_BsyG:0.000):0.000):0.011,28_Bsta:0.000):0.053,29_BsyG:0.000):0.036,(30_Barb:0.005,(31_Bpho:0.024,(32_BsyC:0.000,33_BsyE:0.000):0.027):0.029):0.000):0.005,34_Bboi:0.030):0.035);

Invocando el script lo enraizamos con el taxón elegido, el outgroup '_Sbic':

$ perl reroot_tree.pl unrooted.ph > rooted.ph

Obtenemos el fichero rooted.ph, que podemos visualizar con FigTree:

Árbol enraizado y con orden creciente de nodos.
Éste es el código de reroot_tree.pl :

 #!/usr/bin/perl -w  
   
 # Re-roots an input Newick tree with a user-defined outgroup and   
 # prints the resulting tree in ascending or descending node order.  
 # Based on https://github.com/phac-nml/snvphyl-tools/blob/master/rearrange_snv_matrix.pl  
   
 use strict;  
 use Bio::TreeIO;  
 use Bio::Phylo::IO;  
 use Bio::Phylo::Forest::Tree;  
    
 my $OUTGROUPSTRING = '_Sbic'; # change as needed  
 my $NODEORDER = 1; # 1:increasing, 0:decreasing  
 my ($outfound,$outnode,$sorted_newick) = (0);  
   
 die "# usage: $0 <tree.newick>\n" if(!$ARGV[0]);  
   
 # read input tree  
 my $input = new Bio::TreeIO(-file=>$ARGV[0],-format=>'newick');  
 my $intree = $input->next_tree();  
   
 # find outgroup taxon  
 for my $node ( $intree->get_nodes() ) {   
  if(defined($node->id()) && $node->id() =~ m/$OUTGROUPSTRING/) {  
   $outnode = $node;   
   $outfound = 1;  
   last;  
  }  
 }  
 if($outfound == 0) {  
  die "# cannot find outgroup $OUTGROUPSTRING in input tree $ARGV[0]\n";  
 }  
   
 # root in outgroup and sort in increasing order  
 $intree->reroot_at_midpoint($outnode);  
   
 # sort nodes in defined order and print  
 my $unsorted_tree = Bio::Phylo::IO->parse(  
  '-string' => $intree->as_text('newick'),  
  '-format' => 'newick'  
 )->first();  
   
 $unsorted_tree->ladderize($NODEORDER);  
   
 $sorted_newick = $unsorted_tree->to_newick();  
 $sorted_newick =~ s/'//g;  
   
 print $sorted_newick;  


Un saludo,
Bruno