Biology subjects

Rajamaki, K.

Publications and source records attributed to Rajamaki, K..

3 recordsLinked to original sources

bioRxiv2025

OMIDIENT: Multiomics Integration for Cancer by Dirichlet Auto-Encoder Networks

To achieve a more comprehensive understanding of cancer, novel computational methods are required for the integrative analysis of data from different molecular layers, such as genomics, transcriptomics, and epigenomics. Here, we present a novel multi-omics integrative method that performs unsupervised representation learning, referred to as OMIDIENT: multiOMics Integration for cancer by DIrichlet auto-ENcoder neTworks. OMIDIENT provides a natural framework for modeling sparse and compositional latent representations by employing a deep generative model, where the latent space is distributed as the product of Dirichlet distributions. Applied to five different cancers, we demonstrate that OMIDIENT outperforms the top state-of-the-art unsupervised multi-omics integrative analysis approaches in clustering, classification, and reconstruction of missing data using mRNA expression data, DNA methylation data, and microRNA expression data. Furthermore, we provide interpretability analyses for OMIDIENT that not only support its improved performance, but also offer valuable insights into the underlying structure captured by the learned representations.

bioinformatics↗

bioRxiv2023

The origin of intestinal cancer in the context of inflammation

According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, was shown to suppress intestinal stemness. Here, we employed Paneth cells (PCs) as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation. Upon inflammation, PC-specific Apc mutations led to intestinal tumors reminiscent not only of those arising in inflammatory bowel disease (IBD) patients but also of a larger fraction of sporadic colon cancers. The latter is likely due to the inflammatory consequences of Western-style dietary habits, the major colon cancer risk factor. Computational methods designed to predict the cell-of-origin of cancer confirmed that, in a substantial fraction of sporadic colon cancers the cells-of-origin are secretory lineages and not stem cells. One-Sentence SummarySecretory cell lineages trigger tumor formation in the context of the major etiologic colon cancer risk factors.

cancer biology↗

bioRxiv2018

Characterization of novel TMEM173 mutation with additive IFIH1 risk allele

TMEM173 encodes for STING that is a transmembrane protein activated by pathogen or self-derived cytosolic nucleic acids causing its translocation from ER to Golgi, and further to vesicles. Monogenic STING gain-of-function mutations cause early-onset type I interferonopathy, with disease presentation ranging from fatal vasculopathy to mild chilblain lupus. Molecular mechanisms causing the poor phenotypegenotype correlation are presently unclear. Here we report a novel gain-of-function G207E STING mutation causing a distinct phenotype with alopecia, photosensitivity, thyroid dysfunction, and STING-associated vasculopathy with onset in infancy (SAVI) -features; livedo reticularis, nasal septum perforation, facial erythema, bacterial infections and skin vasculitis. Single residue polymorphisms in TMEM173 and an IFIH1 T946 risk allele modify disease presentation in the affected multigeneration family, explaining the varying clinical phenotypes. The G207E mutation causes constitutive activation of inflammation-related pathways in HEK cells, as well as aberrant interferon signature and inflammasome activation in patient PBMCs. Protein-protein interactions further propose impaired cellular trafficking of G207E mutant STING. These findings reveal the molecular landscape of STING and highlight the complex additive effects on the phenotype.\n\nBRIEF SUMMARYNovel gain-of-function mutation in TMEM173, associated with single residue polymorphisms in TMEM173 and IFIH1, causes a distinct clinical phenotype with some shared features of SAVI.

immunology↗