1,721,067 research outputs found
Accurate quantification of the microbiome in the sinus and the bloodstream
No full textDepartment of Biomedical EngineeringSince the microbiome exists across the body, it has been a long time to try to understand the microbiome???s relation between the host???s health and disease. Represented by Human Microbiome Project (HMP) that shows the variety of microbiome exists in human, previous studies are proved there is a myriad of interactions encompassed the host body which includes an immune response, cell differentiation, nerve system, and other fields1???5. However, most studies are focused on the gut microbiome compared to other organs6 which confines understanding of host-microbiome relation. Indeed, a less focused microbiome with various sites also has an important role in host health. For example, the blood microbiome is associated with bloodstream infection (BSI) that extensive danger to human health7. Also, the sinus microbiome is related to rhinosinusitis caused by inflammation of the sinus that prompts asthma and intracranial complications8,9. Additionally, to investigate the host-related microbiome, various kinds of reference files and alignment tools are suggested. However, verification of its product and revision for performance is often neglected. _x000D_
One of the difficult points is extracting the DNA and RNA from the bacterial cell with handling the low microbial load samples. Additionally, the absence of a validated method for microbiome analysis hinders precise comprehension of its nature. Therefore, in this dissertation, I suggest improved methods to overcome the presented problems that exist across the blood and sinus that are related to sampling the low number of the microbiome. Also, by analyzing the bacterial population, I try to reveal the changes in the microbiome that are related to the alteration of the environment that the host provides._x000D_
Here, I devised the method for a precise taxonomy assignment that is confirmed with the ground truth, a mock community. With a naive Bayesian classifier, I point out how to choose the confidence score base on the clustering and refining of the current reference file. Commonly, reference files nomenclate the organisms based on the whole 16S rRNA gene sequence10. However, it is not fit with the ordinary sequencing method. As the general sequencing target is the V34 region of the 16S rRNA gene that only covers two variable regions of the nine, it can lead to unintended output that interrupts correct understanding. Therefore, I performed an accurate result of the taxonomy assignment with a refined reference file and applied it to further studies.ope
Integrative multi-omics analysis for the effect of genetic alterations in cancer xenograft and organoid models
Full text linkDepartment of Biomedical EngineeringDNA damage is a well-recognized factor in the development and progression of cancer. Numerous studies on genetic changes associated with cancer or the DNA repair pathway have been conducted, however, there is still a need for additional research on their function. The establishment of patient-derived xenografts or organoids for the purpose of testing functional genomic approaches is the subject of ongoing research. According to model-specific characteristics, it is not fully understood how these attempts to simulate patient cancer differ from original cancer. To comprehend the distinction between genuine patient cancer and these patient-derived disease models in more depth, multi-omics analysis is required to comprehend the overall genotypes, phenotypes, and environmental variables. Depending on the characteristics of each disease model, distinct omics analysis approaches and factors must be considered. In addition, care must be taken to avoid technical errors when integrating omics data generated by different sequencing equipment. There is currently no golden rule for data integration, but several approaches are being developed.
It is crucial to determine the function of genes linked with the DNA repair pathway because these genes contribute to the induction or prevention of cancer. In chapter 1, I identified the interaction between MRE11 and TRIP13 through proximity labeling combined with the SILAC method which is quantitative proteomics using metabolic labeling. TRIP13 depletion doesn???t affect the nuclease activity and conformation of the MRN complex but directly inhibits the interaction of MDC1 with MRN complex and MDC1 recruitment on the DNA damage site. TRIP13 degradation with mirin treatment shows additive effects on ATM signaling activation. In conclusion, TRIP13 regulates immediate-early DNA damage sensing through MRE11 and ATM signaling independently of mirin.
When assessing the functional genomic approach using patient-derived disease models, it is essential to determine which aspects of the models' correlation to actual cancer should be properly considered. In chapter 2, I found there are a few overlapped deleterious somatic mutations of the PDX model and their original tumor. I suspected novel mutagen exposure during PDX establishment or sample contamination. However, germline mutations of PDX models are well conserved from original tumors, and their mutational signatures of PDX also mimic that of their tumor. Though the number of overlapped mutations between the PDX model and their tumor was few, brain tumor-specific mutations are found in PDX samples. Especially, histone methylation- and cilia-related gene mutations are enriched in PDX samples. While it suggested these mutated genes are needed for maintaining the stemness of brain tumor PDX model or PDX model would be more appropriate for the samples with high heterogeneity, I have presented precautions and considerations in PDX model genome analysis.
Multi-omics analysis that takes into consideration genetic, expressive, and clinical aspects can provide important information for the study of diseases with complicated etiologies, such as cancer, and can contribute to the development of diagnosis and treatment. To utilize colorectal cancer organoids for Companion Diagnostics (CDx), in chapter 3, I characterized patient-derived colorectal cancer (CRC) organoids through well-known genomic markers such as Tumor mutation burden (TMB), Microsatellite instability (MSI) and propose a novel grouping method using sharing same mutation site. The classification of CRC patients was more detailed combined with consensus molecular subtype (CMS) classifications. Additionally, I extract the expression features of the patients who experience recurrence or metastasis after first-line chemotherapy treatment with reference to clinical data. Drug response of CRC organoids by patient group and knockdown of the extracted features in the selected organoids would be validated in further study.
In summary, with this dissertation, I conducted functional research on the DNA repair pathway of cancer-related genes, as well as the genetic analysis between patient-derived xenograft and original tumors, and introduced a novel perspective on the diagnosis and treatment of colorectal cancer patients using patient-derived organoids through multi-omics analysis.ope
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Reassessing the human orthologs of Xenopus genes
No full textIn many cases, the function of Xenopus gene is inferred by the genomic data of other species, such as human, mouse, and zebrafish, due to their high level of conservation. However, although now the Xenopus community has a very good quality of genomic resources, surprisingly, still the identification of human ortholog is challenging. By utilizing the genome of 10 vertebrate species across taxa, and transcriptome of several amphibian species, here I introduced the robust method to identify orthologous gene family for Xenopus genes. Although two-thirds of all genes could be well assigned to a vertebrate-conserved orthologous gene family, the remaining one-third genes are not obviously called for their orthology. This limitation should be aware when the
Xenopus data is analyzed with the resource of other species, such as the Gene Ontology terms of human
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