Clusters of Conserved Beta Cell Marker Genes for Assessment of Beta Cell Phenotype

The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Prediction of Protein Binding Regions in Disordered Proteins

Many disordered proteins function via binding to a structured partner and undergo a disorder-to-order transition. The coupled folding and binding can confer several functional advantages such as the precise control of binding specificity without increased affinity. Additionally, the inherent flexibility allows the binding site to adopt various conformations and to bind to multiple partners. These features explain the prevalence of such binding elements in signaling and regulatory processes. In this work, we report ANCHOR, a method for the prediction of disordered binding regions. ANCHOR relies on the pairwise energy estimation approach that is the basis of IUPred, a previous general disorder prediction method. In order to predict disordered binding regions, we seek to identify segments that are in disordered regions, cannot form enough favorable intrachain interactions to fold on their own, and are likely to gain stabilizing energy by interacting with a globular protein partner. The performance of ANCHOR was found to be largely independent from the amino acid composition and adopted secondary structure. Longer binding sites generally were predicted to be segmented, in agreement with available experimentally characterized examples. Scanning several hundred proteomes showed that the occurrence of disordered binding sites increased with the complexity of the organisms even compared to disordered regions in general. Furthermore, the length distribution of binding sites was different from disordered protein regions in general and was dominated by shorter segments. These results underline the importance of disordered proteins and protein segments in establishing new binding regions. Due to their specific biophysical properties, disordered binding sites generally carry a robust sequence signal, and this signal is efficiently captured by our method. Through its generality, ANCHOR opens new ways to study the essential functional sites of disordered proteins

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Gender differences in how scientists present the importance of their research: observational study.

ObjectivesWomen remain underrepresented on faculties of medicine and the life sciences more broadly. Whether gender differences in self presentation of clinical research exist and may contribute to this gender gap has been challenging to explore empirically. The objective of this study was to analyze whether men and women differ in how positively they frame their research findings and to analyze whether the positive framing of research is associated with higher downstream citations.DesignRetrospective observational study.Data sourcesTitles and abstracts from 101 720 clinical research articles and approximately 6.2 million general life science articles indexed in PubMed and published between 2002 and 2017.Main outcome measuresAnalysis of article titles and abstracts to determine whether men and women differ in how positively they present their research through use of terms such as "novel" or "excellent." For a set of 25 positive terms, we estimated the relative probability of positive framing as a function of the gender composition of the first and last authors, adjusting for scientific journal, year of publication, journal impact, and scientific field.ResultsArticles in which both the first and last author were women used at least one of the 25 positive terms in 10.9% of titles or abstracts versus 12.2% for articles involving a male first or last author, corresponding to a 12.3% relative difference (95% CI 5.7% to 18.9%). Gender differences in positive presentation were greatest in high impact clinical journals (impact factor >10), in which women were 21.4% less likely to present research positively. Across all clinical journals, positive presentation was associated with 9.4% (6.6% to 12.2%) higher subsequent citations, and in high impact clinical journals 13.0% (9.5% to 16.5%) higher citations. Results were similar when broadened to general life science articles published in journals indexed by PubMed, suggesting that gender differences in positive word use generalize to broader samples.ConclusionsClinical articles involving a male first or last author were more likely to present research findings positively in titles and abstracts compared with articles in which both the first and last author were women, particularly in the highest impact journals. Positive presentation of research findings was associated with higher downstream citations

Gender differences in how scientists present the importance of their research: observational study

ObjectivesWomen remain underrepresented on faculties of medicine and the life sciences more broadly. Whether gender differences in self presentation of clinical research exist and may contribute to this gender gap has been challenging to explore empirically. The objective of this study was to analyze whether men and women differ in how positively they frame their research findings and to analyze whether the positive framing of research is associated with higher downstream citations.DesignRetrospective observational study.Data sourcesTitles and abstracts from 101 720 clinical research articles and approximately 6.2 million general life science articles indexed in PubMed and published between 2002 and 2017.Main outcome measuresAnalysis of article titles and abstracts to determine whether men and women differ in how positively they present their research through use of terms such as "novel" or "excellent." For a set of 25 positive terms, we estimated the relative probability of positive framing as a function of the gender composition of the first and last authors, adjusting for scientific journal, year of publication, journal impact, and scientific field.ResultsArticles in which both the first and last author were women used at least one of the 25 positive terms in 10.9% of titles or abstracts versus 12.2% for articles involving a male first or last author, corresponding to a 12.3% relative difference (95% CI 5.7% to 18.9%). Gender differences in positive presentation were greatest in high impact clinical journals (impact factor >10), in which women were 21.4% less likely to present research positively. Across all clinical journals, positive presentation was associated with 9.4% (6.6% to 12.2%) higher subsequent citations, and in high impact clinical journals 13.0% (9.5% to 16.5%) higher citations. Results were similar when broadened to general life science articles published in journals indexed by PubMed, suggesting that gender differences in positive word use generalize to broader samples.ConclusionsClinical articles involving a male first or last author were more likely to present research findings positively in titles and abstracts compared with articles in which both the first and last author were women, particularly in the highest impact journals. Positive presentation of research findings was associated with higher downstream citations