No abstract

Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues.

Reversible interactions between DNA and silica are utilized in the solid phase extraction and purification of DNA from complex samples. Chaotropic salts commonly drive DNA binding to silica, but inhibit DNA polymerase amplification. We studied DNA adsorption to silica using conditions with or without chaotropic salts through bulk depletion and Quartz Crystal Microbalance (QCM) experiments. While more DNA adsorbed to silica using chaotropic salts, certain buffer conditions without chaotropic salts yielded a similar amount of eluted DNA. QCM results indicate that under stronger adsorbing conditions, the adsorbed DNA layer is initially rigid, but becomes viscoelastic within minutes. These results qualitatively agreed with a mathematical model for a multiphasic adsorption process. Buffer conditions that do not require chaotropic salts can simplify protocols for nucleic acid sample preparation. Understanding how DNA adsorbs to silica can help optimize nucleic acid sample preparation for clinical diagnostic and research applications.

Background There is considerable movement in the U.S. to legalize use of cannabis for medicinal purposes. Twenty-three U.S. states and the D.C. have laws that decriminalize use of marijuana for medicinal purposes. Most prior studies of state medical marijuana laws and their association with overall marijuana use, adolescent use, crime rates, and alcohol traffic fatalities, have used a binary coding of whether the state had a medical marijuana law or not. Mixed results from these studies raise the question of whether this method for measuring policy characteristics is adequate. Objectives Our objective was to develop a validated taxonomy of medical marijuana laws that will allow researchers to measure variation in aspects of medical marijuana statutes as well as their overall restrictiveness. Methods/Results We used a modified Delphi technique using detailed and validated data about each state's medical marijuana law. Three senior researchers coded elements of the state laws in initiation of use, quantity allowed, regulations around distribution, and overall restrictiveness. We used 2013 NSDUH data to assess validity of the taxonomy. Results indicate substantial state-level variation in medical marijuana policies. Validation analysis supported the taxonomy's validity for all four dimensions with the largest effect sizes for the quantity allowed in the state's medical marijuana policy. Conclusions/Importance This analysis demonstrates the potential importance of non-dichotomous measurement of medical marijuana laws in studies of their impact. These findings may also be useful to states that are considering medical marijuana laws, to understand the potential impact of characteristics of those laws.

We developed an evidence base of best practices for clinicians to maintain patient-centered communications in the presence of computerized systems in the exam room. Further work includes development and empirical evaluation of evidence-based guidelines to better integrate computerized systems into clinical care.