1. Amino acid sequence encodes protein abundance shaped by protein stability at reduced synthesis costFilip Buric, Sandra Viknander, Xiaozhi Fu, Oliver Lemke, Oriol Gracia Carmona, Jan Zrimec, Lukasz Szyrwiel, Michael Mülleder, Markus Ralser, Aleksej Zelezniak, 2025, izvirni znanstveni članek Povzetek: Understanding what drives protein abundance is essential to biology, medicine, and biotechnology. Driven by evolutionary selection, an amino acid sequence is tailored to meet the required abundance of a proteome, underscoring the intricate relationship between sequence and functional demand. Yet, the specific role of amino acid sequences in determining proteome abundance remains elusive. Here we show that the amino acid sequence alone encodes over half of protein abundance variation across all domains of life, ranging from bacteria to mouse and human. With an attempt to go beyond predictions, we trained a manageable-size Transformer model to interpret latent factors predictive of protein abundances. Intuitively, the model's attention focused on the protein's structural features linked to stability and metabolic costs related to protein synthesis. To probe these relationships, we introduce MGEM (Mutation Guided by an Embedded Manifold), a methodology for guiding protein abundance through sequence modifications. We find that mutations which increase predicted abundance have significantly altered protein polarity and hydrophobicity, underscoring a connection between protein structural features and abundance. Through molecular dynamics simulations we revealed that abundance-enhancing mutations possibly contribute to protein thermostability by increasing rigidity, which occurs at a lower synthesis cost.
Ključne besede: molecular biology, biotechnology, bioinformatics, deep learning, gene expression, synthetic biology, protein abundance, amino acid sequence, evolutionary selection, transformer model, MGEM (Mutation guided by an embedded manifold)
Objavljeno v DiRROS: 17.12.2024; Ogledov: 830; Prenosov: 440
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2. Gene sequence variation data for the publication "Synchronous effective population size changes and genetic stability of forest trees through glacial cycles" : version 1.0Tanja Pyhäjärvi, Francesca Bagnoli, Katharina Budde, Stephen Cavers, Sandra Cervantes, Benjamin Dauphin, Bruno Fady, Patricia Faivre-Rampant, Santiago C. González-Martínez, Delphine Grivet, Felix Gugerli, Véronique Jorge, Chedly Kastallya, Martin Lascoux, Isabelle Lesur Kupin, Pascal Milesi, Dario I. Ojeda, Sanna Olsson, Lars Opgenoorth, Sara Pinosio, Christophe Plomion, Christian Rellstab, Odile Rogier, Simone Scalabrin, Ivan Scotti, Giovanni G. Vendramin, Marjana Westergren, 2023, zaključena znanstvena zbirka raziskovalnih podatkov Povzetek: This dataset contains the gene sequence variation data (vcf files and their tbi index files) of seven forest tree species used in the manuscript "Synchronous effective population size changes and genetic stability of forest trees through glacial cycles". For each species, between 411 and 651 genotyped trees are included, sampled across Europe in at least 20 locations. Several versions are provided. Species included: Pinus sylvestris, Picea abies, Fagus sylvatica, Populus nigra, Quercus petraea, Pinus pinaster, Betula pendula
Ključne besede: gene sequence, variation data, data set
Objavljeno v DiRROS: 07.03.2023; Ogledov: 1574; Prenosov: 1746
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