89 research outputs found
Multiple sequence alignment based on structural properties
No full textA multiple sequence alignment (MSA) is a sequence alignment of three or more biological sequences. Main idea behind multiple sequence alignment is to see the similarities between input sequences, to be able to make phylogenetic analysis and other evolutionary conclusions. We propose a multiple sequence alignment method based on contact maps derived from structural data and network properties. We show that such methods may be useful in creating multiple alignments that can identify domains and similar structures where sequence identity is low
Monkeypox 101 for Pharmacists: What You Need to Know
No full textThis presentation, “Monkeypox 101 for Pharmacists: What You Need to Know,” provides an overview of monkeypox, including epidemiology, transmission, clinical presentation, treatment options, and vaccination strategies, with a focus on the pharmacist’s role in public health response and patient education
An integrative study on the impact of highly differentially methylated genes on expression and cancer etiology.
No full textDNA methylation is an important epigenetic phenomenon that plays a key role in the regulation of expression. Most of the studies on the topic of methylation's role in cancer mechanisms include analyses based on differential methylation, with the integration of expression information as supporting evidence. In the present study, we sought to identify methylation-driven patterns by also integrating protein-protein interaction information. We performed integrative analyses of DNA methylation, expression, SNP and copy number data on paired samples from six different cancer types. As a result, we found that genes that show a methylation change larger than 32.2% may influence cancer-related genes via fewer interaction steps and with much higher percentages compared with genes showing a methylation change less than 32.2%. Additionally, we investigated whether there were shared cancer mechanisms among different cancer types. Specifically, five cancer types shared a change in AGTR1 and IGF1 genes, which implies that there may be similar underlying disease mechanisms among these cancers. Additionally, when the focus was placed on distinctly altered genes within each cancer type, we identified various cancer-specific genes that are also supported in the literature and may play crucial roles as therapeutic targets. Overall, our novel graph-based approach for identifying methylation-driven patterns will improve our understanding of the effects of methylation on cancer progression and lead to improved knowledge of cancer etiology
A novel analysis strategy for integrating methylation and expression data reveals core pathways for thyroid cancer aetiology
No full textBackground: Recently, a wide range of diseases have been associated with changes in DNA methylation levels, which play a vital role in gene expression regulation. With ongoing developments in technology, attempts to understand disease mechanism have benefited greatly from epigenetics and transcriptomics studies. In this work, we have used expression and methylation data of thyroid carcinoma as a case study and explored how to optimally incorporate expression and methylation information into the disease study when both data are available. Moreover, we have also investigated whether there are important post-translational modifiers which could drive critical insights on thyroid cancer genetics. Results: In this study, we have conducted a threshold analysis for varying methylation levels to identify whether setting a methylation level threshold increases the performance of functional enrichment. Moreover, in order to decide on best-performing analysis strategy, we have performed data integration analysis including comparison of 10 different analysis strategies. As a result, combining methylation with expression and using genes with more than 15\% methylation change led to optimal detection rate of thyroid-cancer associated pathways in top 20 functional enrichment results. Furthermore, pooling the data from different experiments increased analysis confidence by improving the data range. Consequently, we have identified 207 transcription factors and 245 post-translational modifiers with more than 15\% methylation change which may be important in understanding underlying mechanisms of thyroid cancer. Conclusion: While only expression or only methylation information would not reveal both primary and secondary mechanisms involved in disease state, combining expression and methylation led to a better detection of thyroid cancer-related genes and pathways that are found in the recent literature. Moreover, focusing on genes that have certain level of methylation change improved the functional enrichment results, revealing the core pathways involved in disease development such asendocytosis, apoptosis, glutamatergic synapse, MAPK, ErbB, TGF-beta and Toll-like receptor pathways. Overall, in addition to novel analysis framework, our study reveals important thyroid-cancer related mechanisms, secondary molecular alterations and contributes to better knowledge of thyroid cancer aetiology.12DEC 91
Image based integrated attitude determination
No full textDetermination of the satellite attitude is one of the critical functions from the moment of launch to the end of the mission. In this study, it has been shown that the satellite attitude can be determined from the Earth and Sun images obtained using cameras in the satellite body and performance of the method has been examined by simulations. In addition, a gyro based integrated attitude determination system has been proposed that uses image based attitude information as a reference measurement
Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766).
No full textDemonstrating intracellular protein target engagement is an essential step in the development and progression of new chemical probes and potential small molecule therapeutics. However, this can be particularly challenging for poorly studied and noncatalytic proteins, as robust proximal biomarkers are rarely known. To confirm that our recently discovered chemical probe 1 (CCT251236) binds the putative transcription factor regulator pirin in living cells, we developed a heterobifunctional protein degradation probe. Focusing on linker design and physicochemical properties, we generated a highly active probe 16 (CCT367766) in only three iterations, validating our efficient strategy for degradation probe design against nonvalidated protein targets
Analysis of the interplay between methylation and expression reveals its potential role in cancer aetiology
No full textWith ongoing developments in technology, changes in DNA methylation levels have become prevalent to study cancer biology. Previous studies report that DNA methylation affects gene expression in a direct manner, most probably by blocking gene regulatory regions. In this study, we have studied the interplay between methylation and expression to improve our knowledge of cancer aetiology. For this purpose, we have investigated which genomic regions are of higher importance; hence, first exon, 5'UTR and 200 bp near the transcription start sites are proposed as being more crucial compared to other genomic regions. Furthermore, we have searched for a valid methylation level change threshold, and as a result, 25 % methylation change in previously determined genomic regions showed the highest inverse correlation with expression data. As a final step, we have examined the commonly affected genes and pathways by integrating methylation and expression information. Remarkably, the GPR115 gene and ErbB signalling pathway were found to be significantly altered for all cancer types in our analysis. Overall, combining methylation and expression information and identifying commonly affected genes and pathways in a variety of cancer types revealed new insights of cancer disease mechanisms. Moreover, compared to previous methylation-based studies, we have identified more important genomic regions and have defined a methylation change threshold level in order to obtain more reliable results. In addition to the novel analysis framework that involves the analysis of four different cancer types, our study exposes essential information regarding the contribution of methylation changes and its impact on cancer disease biology, which may facilitate the identification of new drug targets
Automated Biological Evidence Generation In Drug-Discovery
No full text<p><strong>Automated Biological Evidence Generation In Drug-Discovery</strong></p>
<p>Example code and data samples for "An experimentally validated approach to automated biological evidence generation in drug discovery using knowledge graphs".</p>
<p>This code enables the explanation of predictions for drug repositioning using biological knowledge graphs, using a reinforcement learning-based knowledge graph completion model combined with an automatic filtering approach.</p>
Quarantine Architecture
No full textThe deadly COVID-19 virus is wreaking havoc throughout the globe. In the past two years, architects had to rethink certain forms of spatial organization to contain the spread of the pandemic. This thesis explores how pandemics and deadly diseases were dealt with and shows the forgotten design principles of the past. To prevent infectious diseases from coming ashore and affecting cities, several institutions were established throughout the Netherlands. Quarantine stations are created as architectural representations of isolation with impenetrable areas at a country entrance. This leads to the main question adressed in this thesis: How were Dutch quarantine stations for humans organized from a geographical and architectural point of view?This study first looks at the origin of quarantine stations. Furthermore, research is done into the legislation and policy in the Netherlands. This part explains the reason for building Quarantine Stations in the Netherlands. Finally, Quarantine Station Heijplaat and two additional Dutch stations are researched as a case study.AR2A011Architecture, Urbanism and Building Science
Upscaling Dementia Architecture: A study about aging in place with dementia
No full textDespite the predicted increase in the number of dementia patients, the Dutch government has opted against building any extra nursing facilities in the future. Individuals, families, healthcare institutions, and society as a whole may suffer as a result of persons with dementia remaining in their homes or neighborhoods that are unsuitable for their needs.Making existing neighborhoods dementia-friendly will result in a safe and inclusive living environment, which is required to accommodate the rising number of dementia patients and avoid future issues. Architectural solutions and small-scale initiatives can help reduce the progression of dementia and enhance the quality of life. Meaningful and supportive settings in neighborhoods or households improve health. Giving people environmental control and fostering strong communal bonds positively impacts their well-being. Implementing these procedures guarantees that the elderly with dementia can live in their own homes for as long as possible.Architecture, Urbanism and Building Science
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