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Implementation of the agnostic approach, however, has not yet been fully achieved. In particular, agnostic mapping of pre-mRNA splice sites has not been demonstrated. The present study pursued dual goals: 1 to advance mRNA-seq bioinformatics toward unbiased transcriptome capture and 2 to demonstrate its potential for discovery in neuroscience by applying the approach to an in vivo model of neurological disease.
We found that These alterations persisted chronically 2 mo. Integration of information from all mRNA-seq read classes including SJs led to genome reannotations specifically relevant for the species used rat , the anatomical site studied DRG , and the neurological disease considered pain ; for example, a exon coreceptor for the nociceptive transmitter substance P was identified, and Thus, mRNA-seq with agnostic analysis methods appears to provide a highly productive approach for in vivo transcriptomics in the nervous system.
Microarray-based transcriptome studies have provided a productive approach to the discovery of therapeutic targets in neurological disorders. For example, gene expression profiling of the dorsal root ganglion DRG in chronic pain Griffin et al. Gene expression analysis using microarray technology suffers from well-known limitations including poor sensitivity and dynamic range, a requirement for substantial requisite amounts of RNA, and a limited capacity to identify new transcripts or RNA splice sites.
Given these limitations, it is unlikely that microarray analysis can reveal the full extent of transcriptome reprogramming underlying neurological disorders, such as chronic pain. Ultra-high-throughput RNA sequencing has emerged as a revolutionary technology with superior dynamic range and reproducibility compared with microarrays Marioni et al. Conceptually, ultra-high-throughput mRNA sequencing mRNA-seq should be capable of overcoming virtually all limitations of microarray technology by permitting de novo capture of the full transcriptome of any experimental tissue.
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I have never been a big fan of religion. Even at a young age, I thought God and heaven were pacifying ideas to keep people from being afraid of death. Though my judgments of Christianity and belief have evolved to a more nuanced understanding, my lack of faith has not changed. Marriage is all about compromise, right? He believed that an omniscient being watches over us, that when we died we would be together again in an otherworldly place, and that praying for people was an important part of caring for them.
He was Christian-lite: just enough for me to respect it, and more important, to live with it. He went on to voice all the conflicting ideas and emotions he had been dealing with as he scrutinized his faith, notions I had examined in my own spiritual quest that ended in agnosticism during my college years. Fred was traveling the same path, only 11 years behind me. But inside I was in turmoil. When it came to religion, we were suddenly in agreement. Christians and religious zealots might say that deep down I was searching for a sense of peace that only the Lord can provide.
Maybe, but I doubt it. But I did realize I liked the comfort of other people believing, especially my other half. It made me feel safe.
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Reviews August 2020
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In an era of increased focus on precision medicine, tumour-agnostic therapies have emerged as a revolutionary new approach to cancer treatment. Tumour-agnostic therapies target specific genomic anomalies or molecular features regardless of tumour site of origin. Pan-tumour approaches signal an important new paradigm in clinical management, whereby tumour genomic signature supersedes histology in informing treatment decisions.