Biology subjects

Lopes-Ramos, C.

Publications and source records attributed to Lopes-Ramos, C..

4 recordsLinked to original sources

bioRxiv2025

Sex differences in thyroid aging and their implications in thyroid disorders: insights from gene regulatory networks

Thyroid disorders are more prevalent in females than males, with sex differences in disease risk varying by age, e.g. although risk of anaplastic thyroid carcinoma (ATC) increases with age for both sexes, females are diagnosed at younger ages than males. In contrast, Hashimotos thyroiditis (HT) is more common in ages 30-50, with females having higher risk. These patterns suggest that in thyroid, gene regulatory processes evolve with age in a sex-specific manner. To characterize these sex differences in thyroid aging, we estimated and analyzed individual-specific gene regulatory networks using BONOBO and PANDA algorithms. We found that regulatory patterns of pathways involved in cell proliferation, immune response, and metabolic processes vary nonlinearly with age, with sex-specific differences in direction and rate. Females show two inflection points around ages 40 and 60, when regulatory patterns show significant change for most pathways, consistent with changes in targeting by estrogen and androgen receptors. Investigating gene regulatory patterns in HT and ATC, we observed that disease-relevant immune and metabolic pathways changed with age in the same direction as they change in ATC. In contrast, in HT, disease-related regulatory patterns are in the opposite direction of aging. In age groups where HT is most diagnosed, regulatory patterns in females more closely resembled disease states than males, highlighting sex-biased regulations role in elevated disease risk in females. Our findings demonstrate immune response and metabolic processes are regulated in age- and sex-specific manner, potentially driving variation in disease risk, emphasizing the need for tailored screening and prevention strategies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/684890v3_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@cd93aeorg.highwire.dtl.DTLVardef@9a913aorg.highwire.dtl.DTLVardef@1b4a862org.highwire.dtl.DTLVardef@19adca8_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2025

Identifying Sex Differences in Lung Adenocarcinoma Using Multi-Omics Integrative Protein Signaling Networks

Lung adenocarcinoma (LUAD) exhibits differences between the sexes in incidence, prognosis, and therapy, suggesting underexplored molecular mechanisms. We conducted an integrative multi-omics analysis using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) datasets to contrast transcriptomes and proteomes between sexes. We used TIGER to analyze TCGA-LUAD expression data and found sex-biased activity of transcription factors (TFs); we used PTM-SEA with CPTAC-LUAD proteomics data and found sex-biased kinase activity. We combined these to construct a kinase-TF signaling network and discovered druggable pathways linked to cancer-related processes. We also found significant sex biases in clinically relevant TFs and kinases, including NR3C1, AR, and AURKA. Using the PRISM drug screening database, we identified potential sex-specific drugs, such as glucocorticoid receptor agonists and aurora kinase inhibitors. Our findings emphasize the importance of considering sex and using multi-omics network methods to discover personalized cancer therapies.

cancer biology↗

bioRxiv2024

Selective loss of Y chromosomes in lung adenocarcinoma modulates the tumor immune environment through cancer/testis antigens

There is increasing recognition that the allosomes, X and Y, play an important role in health and disease beyond the determination of biological sex. A loss of the Y chromosome (LOY) occurs in most solid tumors in males and is often associated with worse survival, suggesting that LOY may give tumor cells a growth or survival advantage. We here use an expression-based continuous measure of LOY that allows us to investigate LOY in lung adenocarcinoma (LUAD) using both bulk and single-cell expression data. We find evidence suggesting that LOY affects the tumor immune environment by altering cancer/testis antigen expression and consequently facilitating tumor immune evasion, also reflected in inferred gene regulatory networks. In immunotherapy data, we further show that LOY and changes in expression of particular cancer/testis antigens are associated with response to pembrolizumab treatment and outcome. This computational study provides new insights into the mechanisms behind LOY in LUAD and a powerful biomarker for predicting immunotherapy response in LUAD tumors in males.

cancer biology↗

bioRxiv2020

Gene Regulatory Network Inference as Relaxed Graph Matching

Gene regulatory network inference is instrumental to the discovery of genetic mechanisms driving diverse diseases, including cancer. Here, we present a theoretical framework for PANDA, an established method for gene regulatory network inference. PANDA is based on iterative message passing updates that resemble the gradient descent of an optimization problem, OTTER, which can be interpreted as relaxed inexact graph matching between a gene-gene co-expression and a protein-protein interaction matrix. The solutions of OTTER can be derived explicitly and inspire an alternative spectral algorithm, for which we can provide network recovery guarantees. We compare different solution approaches of OTTER to other inference methods using three biological data sets, which we make publicly available to offer a new application venue for relaxed graph matching in gene regulatory network inference. We find that using modern gradient descent methods with superior convergence properties solving OTTER outperforms state-of-the-art gene regulatory network inference methods in predicting binding of transcription factors to regulatory regions.

bioinformatics↗