[b\u00fasqueda PubMed automatizada]<\/small><\/p>\n
2026<\/strong><\/p>\n\n\n\n\t\n\n\tSite-Specific Structure and Stability Constrained Substitution Models Improve Phylogenetic Inference<\/div>\n\n\n\tLorca-Alonso I, Otero-de-Navascues F, Arenas M<\/span> and Bastolla U<\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Syst Biol<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tSite-Specific Structure and Stability Constrained Substitution Models Improve Phylogenetic Inference<\/div>\n\n\n\tLorca-Alonso I, Otero-de-Navascues F, Arenas M<\/span> and Bastolla U<\/div>\n\n\n In previous studies, we presented our site-specific Stability Constrained substitution models of Protein Evolution (Stab-CPE) that define fitness as the probability of finding a protein folded in its native state but ignore changes in the native structure. Stab-CPE models can be used to predict a more realistic evolutionary variability across protein sites, nevertheless they still qualitatively differ from observed data and appear too tolerant to mutations. Here, we present novel structurally constrained substitution models (Str-CPE) that define fitness based on the structural deformation produced by a mutation, which we predict adopting an extension of Juli\u00e1n Echave's linearly forced elastic network model. Compared with our previous Stab-CPE models, the novel Str-CPE models are more stringent (they predict lower sequence entropy and substitution rate), provide higher likelihood to multiple sequence alignments (MSAs) that include one or more known structures, and better predict the observed conservation across sites. The models that combine Str-CPE and Stab-CPE models are even more stringent and fit the empirical MSAs better. We collectively refer to our models as Structure and Stability Constrained substitution models of Protein Evolution (SSCPE). When using distantly related proteins, we find that more similar phylogenies are inferred under the SSCPE models than under traditional empirical substitution models if compared with the corresponding reference phylogenies inferred using structural distances. Therefore, SSCPE models seem to be much better-fitting substitution models for deep phylogeny inference. The SSCPE models have been implemented in the PERL-based program SSCPE.pl, which uses RAxML-NG to infer phylogenies under the SSCPE model given a concatenated MSA and a list of protein structures that match the sequences in the MSA. This program is freely available and downloadable from https:\/\/gihub.com\/ugobas\/SSCPE.<\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Syst Biol<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n\n\n\t\n\n\tPyrimidine-based compounds as promising anticancer agents targeting tumor cell senescence<\/div>\n\n\n\tCarpintero-Fern\u00e1ndez P, Mart\u00ednez MM, Carneiro-Figueira A, Mart\u00ednez R, Garc\u00eda-Yuste A, Barturen-G\u00f3mez M, P\u00e9rez-Caaveiro C, Guiti\u00e1n-Caama\u00f1o A, Sarandeses LA, Sestelo JP and May\u00e1n MD<\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Mol Ther Oncol<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tPyrimidine-based compounds as promising anticancer agents targeting tumor cell senescence<\/div>\n\n\n\tCarpintero-Fern\u00e1ndez P, Mart\u00ednez MM, Carneiro-Figueira A, Mart\u00ednez R, Garc\u00eda-Yuste A, Barturen-G\u00f3mez M, P\u00e9rez-Caaveiro C, Guiti\u00e1n-Caama\u00f1o A, Sarandeses LA, Sestelo JP and May\u00e1n MD<\/div>\n\n\n The pyrimidine ring is an important structural motif present in numerous bioactive compounds, including those with antibacterial and antitumor activities. In this study, two novel 4,6-disubstituted-2-(4-morpholinyl) pyrimidines (P12 and P14) were evaluated in breast cancer and melanoma cells with different genetic backgrounds. Both compounds demonstrated antitumor activity by reducing cell proliferation in 2D and 3D models. Mechanistic studies showed that these derivatives induce cell-cycle delay, altering the transcription of key cell-cycle mediators and leading to a senescent-like phenotype accompanied by changes in the pattern of the senescence-associated secretory phenotype (SASP). In addition, both compounds appeared to induce cell death, potentially in distinct tumor cell subpopulations. Collectively, these findings highlight the potential of pyrimidine-based derivatives as lead compounds for the development of pro-senescent anticancer agents, with utility in cancers where senescence plays a critical role, such as BRAF-mutant melanoma and the ER+\/HER2- breast cancer subtype investigated in this study.<\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Mol Ther Oncol<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n\n\n\t\n\n\tA circulating MicroRNA signature for the diagnosis of pulmonary arterial hypertension and functional characterization of candidate miR-3168<\/div>\n\n\n\tLago-Docampo M, Iglesias-L\u00f3pez A, Vilari\u00f1o C, Baloira A, Barber\u00e1 JA, Blanco I and Valverde D<\/span><\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Sci Rep<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tA circulating MicroRNA signature for the diagnosis of pulmonary arterial hypertension and functional characterization of candidate miR-3168<\/div>\n\n\n\tLago-Docampo M, Iglesias-L\u00f3pez A, Vilari\u00f1o C, Baloira A, Barber\u00e1 JA, Blanco I and Valverde D<\/span><\/div>\n\n\n Pulmonary Arterial Hypertension (PAH) is a rare, progressive disorder characterized by pathological vascular remodeling of the pulmonary arteries, ultimately leading to right heart failure. Early diagnosis remains challenging, as clinical manifestations are often nonspecific, and definitive confirmation still requires invasive right heart catheterization. Circulating microRNAs (miRNAs) have emerged as promising biomarkers for cardiovascular diseases due to their plasma stability and direct involvement in disease pathophysiology. We performed small RNA sequencing on plasma samples from 25 IPAH patients and 10 healthy controls to identify differentially expressed miRNAs. Seven candidate miRNAs were selected for further validation by quantitative PCR in a multicenter cohort of 110 IPAH patients and controls. Logistic regression models were built to evaluate diagnostic performance. Functional studies for miR-3168 were performed using western blot and flow cytometry in Pulmonary Artery Endothelial Cells (PAECs), and tube formation assay in human umbilical vein endothelial cells (HUVECs). Our initial screen identified 29 differentially expressed miRNAs. Seven of these candidates, including members of the let-7 family and miR-3168, were successfully validated in the larger cohort. A diagnostic panel incorporating three miRNAs (let-7a-5p, miR-9-5p, and miR-31-5p) was developed, which achieved an area under the curve (AUC) of 0.862 (95% CI\u2009=\u20090.7481-1) for discriminating PAH patients from controls. Separately, we investigated the functional role of miR-3168, which was upregulated in PAH patients. In PAECs, overexpression of miR-3168 led to a reduction of BMPR2 protein levels. Moreover, miR-3168 overexpression impaired tube formation in HUVECs. Our study identifies a plasma-derived three-miRNA signature with strong potential for the non-invasive diagnosis of PAH. Furthermore, we implicate miR-3168 as a potential contributor to endothelial dysfunction through its regulation of BMPR2 and its anti-angiogenic effects in vitro. These findings reinforce the dual utility of circulating miRNAs as both clinically relevant non-invasive biomarkers and as tools to discover novel disease biology.<\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Sci Rep<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n\n\n\t\n\n\tAuthor Correction: The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture<\/div>\n\n\n\tVazquez N, Lee C, Valenzuela I, Phan TP, Derderian C, Ch\u00e1vez M, Mooney NA, Demeter J, Aziz-Zanjani MO, Cusco I, Codina M, Mart\u00ednez-Gil N, Valverde D<\/span>, Solarat C, Bruel AL, Thauvin-Robinet C, Steichen E, Filges I, Joset P, De Geyter J, Vaidyanathan K, Gardner TP, Toriyama M, Marcotte EM, Drew K, Roberson EC, Jackson PK, Reiter JF, Tizzano EF and Wallingford JB<\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Nat Commun<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tAuthor Correction: The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture<\/div>\n\n\n\tVazquez N, Lee C, Valenzuela I, Phan TP, Derderian C, Ch\u00e1vez M, Mooney NA, Demeter J, Aziz-Zanjani MO, Cusco I, Codina M, Mart\u00ednez-Gil N, Valverde D<\/span>, Solarat C, Bruel AL, Thauvin-Robinet C, Steichen E, Filges I, Joset P, De Geyter J, Vaidyanathan K, Gardner TP, Toriyama M, Marcotte EM, Drew K, Roberson EC, Jackson PK, Reiter JF, Tizzano EF and Wallingford JB<\/div>\n\n\n <\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Nat Commun<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n\n\n\t\n\n\tCancer evolution and multi-omic profile of relapsed colorectal liver metastases after treatment<\/div>\n\n\n\tTom\u00e1s L, Raschzok N, Blanc E, Gallardo-G\u00f3mez M, Menne A, Astrahantseff K, De Chiara L, Geisel D, Pratschke J, Modest DP, Eggert A, Beule D, Posada D<\/span>, Sers C and Mamlouk S<\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Genome Med<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tCancer evolution and multi-omic profile of relapsed colorectal liver metastases after treatment<\/div>\n\n\n\tTom\u00e1s L, Raschzok N, Blanc E, Gallardo-G\u00f3mez M, Menne A, Astrahantseff K, De Chiara L, Geisel D, Pratschke J, Modest DP, Eggert A, Beule D, Posada D<\/span>, Sers C and Mamlouk S<\/div>\n\n\n Recurrence following resection of colorectal cancer liver metastases remains a major obstacle to prolonged patient survival, often resulting in treatment-refractory disease with limited understanding of the underlying evolutionary drivers. To investigate these mechanisms, we performed an in-depth, patient-specific study of genomic and microenvironmental alterations in relapsed colorectal cancer liver metastases from nine individuals.<\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Genome Med<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n\n\n\t\n\n\tUnraveling the Phylogenetic Signal of Gene Expression from Single-cell RNA-seq Data<\/div>\n\n\n\tAlves JM, Tom\u00e1s L and Posada D<\/span><\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Genomics Proteomics Bioinformatics<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tUnraveling the Phylogenetic Signal of Gene Expression from Single-cell RNA-seq Data<\/div>\n\n\n\tAlves JM, Tom\u00e1s L and Posada D<\/span><\/div>\n\n\n Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of phenotypic heterogeneity. Although the predominant focus of scRNA-seq analyses has been assessing gene expression changes, several approaches have been proposed in recent years to identify changes at the DNA level from scRNA-seq data. In this study, we evaluated the relative performance of six strategies for calling single-nucleotide variants from scRNA-seq data using 381 single-cell transcriptomes from five cancer patients. Specifically, we focused on the quality of the inferred genotypes and the resulting single-cell phylogenies. We found that scAllele, Monopogen, and Monovar consistently returned phylogenetically informative genotype calls, providing more precise signals of discrimination between tumor and normal cells within heterogeneous samples and among distinct subclonal lineages in longitudinal samples. In addition, we evaluated the evolution of gene expression along the cell phylogenies. While most transcriptomic variation was very plastic and did not correlate with the cell phylogeny, a group of genes associated with cell cycle processes showed a strong phylogenetic signal in one of the patients, underscoring a potential link between gene expression patterns and lineage-specific traits in the context of cancer progression. In summary, our study highlights the potential of scRNA-seq data for inferring cell phylogenies to decipher the evolutionary dynamics of cell populations.<\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Genomics Proteomics Bioinformatics<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n\n\n\t\n\n\tTrends in substitution models of protein evolution for phylogenetic inference<\/div>\n\n\n\tFerreiro D, Pazos E and Arenas M<\/span><\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Mol Phylogenet Evol<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tTrends in substitution models of protein evolution for phylogenetic inference<\/div>\n\n\n\tFerreiro D, Pazos E and Arenas M<\/span><\/div>\n\n\n Substitution models of protein evolution describe the rates of evolutionary change among amino acids and are essential for a variety of evolutionary studies, including the reconstruction of phylogenetic histories and ancestral sequences, among others. The earliest substitution models of protein evolution are based on empirical protein sequences and, despite their unrealistic assumptions, are still routinely used in protein phylogenetics. Next, the incorporation of additional parameters that inform about evolutionary constraints on protein stability and protein function provided a significant increase in the accuracy of the modeling. However, despite the wide variety of substitution models of protein evolution that were presented, only a small subset has been implemented in evolutionary frameworks of practical use in phylogenetics. Here, we overview general trends in the development and application of substitution models of protein evolution, including their theoretical fundamentals, goals, areas for improvement, and implementation in phylogenetic frameworks. We also provide detailed practical examples of phylogenetic inference using advanced structurally constrained substitution models.<\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Mol Phylogenet Evol<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n\n\n\t\n\n\tA comparison of methods for the optimal recovery of the human fecal virome<\/div>\n\n\n\tDe Chiara L, Doughty R, Est\u00e9vez-G\u00f3mez N, Gallego-Garc\u00eda P, Alvari\u00f1o P, D\u00edez-Mart\u00edn A, D\u00e1vila Pi\u00f1\u00f3n P, Treangen TJ, Cubiella J and Posada D<\/span><\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n ISME Commun<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tA comparison of methods for the optimal recovery of the human fecal virome<\/div>\n\n\n\tDe Chiara L, Doughty R, Est\u00e9vez-G\u00f3mez N, Gallego-Garc\u00eda P, Alvari\u00f1o P, D\u00edez-Mart\u00edn A, D\u00e1vila Pi\u00f1\u00f3n P, Treangen TJ, Cubiella J and Posada D<\/span><\/div>\n\n\n Human virome research is gaining increasing attention as viruses are recognized as critical modulators of microbial communities and human health. Viral metagenomics, however, faces unique challenges, including the low abundance and diversity of viruses in biological samples, the absence of universal marker genes, and biases introduced by experimental protocols. While various virome protocols have been benchmarked using viral particles or nucleic acids from mock communities, these approaches often fail to capture the complexity and heterogeneity of natural viromes. In this study, we systematically evaluated modifications to key methodological steps in the metagenomic analysis of human fecal samples, including viral enrichment, nucleic acid extraction, genome amplification, and library preparation. Using gold-standard bioinformatic approaches on sequencing datasets generated after amplification, we assessed the impact of these modifications on relative viral taxonomic assignment, contig quality, richness, diversity, and inferred genome structure. Our findings reveal striking trade-offs between recovery of viral genomes and retention of nonviral sequences, demonstrating how methodological choices can shape the inferred virome composition. Based on these observations, we propose an optimized protocol that enhances viral genome recovery while reducing contamination from nonviral sequences. This refined workflow provides a more robust and reliable framework for gut virome studies, paving the way for a deeper exploration of the role of viruses in human health and microbial ecosystems.<\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n ISME Commun<\/a>\n <\/div>\n \n PMC Article<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n\n\n\t\n\n\tWhole-Genome Amplification of Single Circulating Tumor Cells from Mice Xenografts<\/div>\n\n\n\tEst\u00e9vez-G\u00f3mez N, Fern\u00e1ndez-Santiago C, Pi\u00f1eiro R and Posada D<\/span><\/div>\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Methods Mol Biol<\/a>\n <\/div>\n <\/div>\n\n \n\t\t\n\n\tWhole-Genome Amplification of Single Circulating Tumor Cells from Mice Xenografts<\/div>\n\n\n\tEst\u00e9vez-G\u00f3mez N, Fern\u00e1ndez-Santiago C, Pi\u00f1eiro R and Posada D<\/span><\/div>\n\n\n The genomic analysis of circulating tumor cells (CTCs) can help us identify their specific characteristics and reveal intratumor heterogeneity while also reducing the need for invasive sampling. However, studying single CTCs can be challenging, as whole-genome amplification (WGA) is needed to obtain enough genetic material for high-throughput sequencing. Here, we present a protocol for isolating single CTCs from mouse xenografts, followed by WGA using the Ampli1WGA Plus kit.<\/div>\n\n\n\n \n Abstract<\/a>\n <\/div>\n View more: <\/div>\n\t \n Pubmed<\/a>\n <\/div>\n \n Methods Mol Biol<\/a>\n <\/div>\n <\/div>\n\n <\/div>\n\n<\/div>\n\n\n2025<\/strong><\/p>\n\n\n\n\t\n\n\tTrends in substitution models of protein evolution for phylogenetic inference<\/div>\n\n\n\tFerreiro D, Pazos E and
2025<\/strong><\/p>\n\n\n\n\t\n\n\tTrends in substitution models of protein evolution for phylogenetic inference<\/div>\n\n\n\tFerreiro D, Pazos E and