There are two frameworks for characterizing mutational signatures which are commonly used to describe the nucleotide patterns that arise from mutational processes. Estimated mutational signatures from fitting these two methods in human cancer can be found online, in the Catalogue Of Somatic Mutations In Cancer (COSMIC) website or a GitHub repository. The two frameworks make differing assumptions regarding independence of base pairs and for that reason may produce different results. Consequently, there is a need to compare and contrast the results of the two methods, but no such tool currently exists. In this paper, we provide a simple and intuitive interface that allows comparisons of pairs of mutational signatures to be easily performed. Cosine similarity measures the extent of signature similarity. To compare mutational signatures of different formats, one signature type (COSMIC or ) is converted to the format of the other before the signatures are compared. provides a simple and user-friendly web application allowing researchers to download published mutational signatures of either type and to compare signatures from COSMIC to those from , and vice versa. Furthermore, allows users to input a self-defined mutational signature and examine its similarity to published signatures from both data sources. is accessible online and source code is available for download from GitHub.
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http://dx.doi.org/10.12688/f1000research.24435.2 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
Innate immunity relies on Toll-like receptors (TLRs) to detect pathogen-associated molecular patterns. The TIR (Toll/interleukin-1 receptor) domain-containing TLR adaptors TRIF (TIR domain-containing adaptor-inducing interferon-β) and TRAM (TRIF-related adaptor molecule) are essential for MyD88-independent TLR signaling. However, the structural basis of TRIF and TRAM TIR domain-based signaling remains unclear.
View Article and Find Full Text PDFCancer Res
December 2024
Rutgers, The State University of New Jersey, New Brunswick, NJ, United States.
Mutations in the exonuclease domains of the replicative nuclear DNA polymerases POLD1 and POLE are associated with increased cancer incidence, elevated tumor mutation burden (TMB), and enhanced response to immune checkpoint blockade (ICB). Although ICB is approved for treatment of several cancers, not all tumors with elevated TMB respond, highlighting the need for a better understanding of how TMB affects tumor biology and subsequently immunotherapy response. To address this, we generated mice with germline and conditional mutations in the exonuclease domains of Pold1 and Pole.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
Background: [F]FDG PET is essential since it allows us to differentiate between different dementia disorders/types, revealing distinct neurodegenerative patterns in those predisposed to the condition. Individuals with Autosomal Dominant Alzheimer's Disease (ADAD) have a predictable age of onset, enabling the study of cognitive and pathological changes before clinical manifestation. Our objective was to investigate temporal course and regional links between cognition and glucose metabolism as a measure of early synaptic impairment in ADAD.
View Article and Find Full Text PDFBackground: In people with Parkinson's disease (PD), mutations in GBA and LRRK2 are associated with different clinical phenotypes which might be related to differential involvement of the cholinergic system. We aimed to investigate cholinergic basal forebrain (cBF) volume in asymptomatic and symptomatic mutation carriers in comparison to idiopathic PD and healthy controls and associations with cognitive decline.
Method: This study included 149 asymptomatic GBA and 169 asymptomatic LRRK2 mutation carriers, 112 LRRK2 carriers and 60 GBA carriers with PD, 492 idiopathic PD, and 180 healthy controls from the Parkinson's Progression Markers Initiative (PPMI).
Alzheimers Dement
December 2024
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Clinical Neurophysiology and MEG Center, Neurology, De Boelelaan 1117, Amsterdam, Netherlands.
Background: An early disruption in excitation-inhibition (E-I) balance is believed to underlie abnormal local and global network dynamics in Alzheimer's disease (AD). While prior studies proposed that changes in E-I balance may underlie the established slowing of oscillatory activity and changes in functional connectivity in symptomatic AD, the specific alterations occurring in the presymptomatic stage of AD remain poorly understood. This study aims to identify local and global spectral power and functional connectivity changes in individuals with familial AD before the onset of clinical symptoms.
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