1,721,084 research outputs found
A Genomic map of positive selection in Sardinia
Full text linkThe recent production of population-scale genomic data offers an unprecedented opportunity to understand how natural selection has shaped human phenotypic variation within populations. To identify signatures of recent positive selection in Sardinia, we used 23 million single nucleotide polymorphisms from low-coverage whole genomes of 3,514 Sardinians along with data from the 1000 Genomes project. Using single-population (iHS, nSL) and cross-population (Fst, PBS, XP-EHH) based statistics, we found many genetic regions showing evidence of positive selection.
We found that selection statistics computed for outlier variants cannot be explained by neutral forces alone. By intersecting genome-wide association study data for hundreds of traits measured in Sardinians with publicy available functional genomic databases, we found that autoimmunity-related genes are enriched for these putatively adaptive variants.Taken together, these results illustrate the importance of characterizing the phenotypic variation within a population, and especially the utility of whole-genome-sequence data, when proposing and interpreting genetic signatures of positive selection
Overview of the First 6 Months of Clinical Trials for COVID-19 Pharmacotherapy: The Most Studied Drugs
No full textSARS-CoV-2 rapidly spread from China until it was defined a pandemic by WHO in March 2020. Related scientific papers have rapidly extended information regarding the diagnosis, treatment and epidemiology of COVID-19 infection. To date, no vaccine or definitive treatment is available to defeat the virus and therapies are mainly based on existing drugs used to treat other conditions. Existing therapies used in several clinical trials work by affecting the biology of COVID-19 and/or counteracting the harmful host excessive immune response. Here, we have reviewed 526 ongoing clinical trials for COVID-19 to provide a perspective on the first 6 months of global efforts to identify an effective therapy. The drugs most actively tested in various centers include hydroxychloroquine, ritonavir, azithromycin, tocilizumab, lopinavir chloroquine and ivermectin. Our analysis shows that most clinical trials focus on a small number of candidate drugs (namely hydroxychloroquine and chloroquine representing 25% of total clinical trials) while underestimating the potential of other promising drugs. A global coordination in clinical trial management could avoid duplications and increase the effectiveness of the response to the global challenge
Splice-mediated Variants of Proteins (SpliVaP) – data and characterization of changes in signatures among protein isoforms due to alternative splicing
Full text linkAbstract Background It is often the case that mammalian genes are alternatively spliced; the resulting alternate transcripts often encode protein isoforms that differ in amino acid sequences. Changes among the protein isoforms can alter the cellular properties of proteins. The effect can range from a subtle modulation to a complete loss of function. Results (i) We examined human splice-mediated protein isoforms (as extracted from a manually curated data set, and from a computationally predicted data set) for differences in the annotation for protein signatures (Pfam domains and PRINTS fingerprints) and we characterized the differences & their effects on protein functionalities. An important question addressed relates to the extent of protein isoforms that may lack any known function in the cell. (ii) We present a database that reports differences in protein signatures among human splice-mediated protein isoform sequences. Conclusion (i) Characterization: The work points to distinct sets of alternatively spliced genes with varying degrees of annotation for the splice-mediated protein isoforms. Protein molecular functions seen to be often affected are those that relate to: binding, catalytic, transcription regulation, structural molecule, transporter, motor, and antioxidant; and the processes that are often affected are nucleic acid binding, signal transduction, and protein-protein interactions. Signatures are often included/excluded and truncated in length among protein isoforms; truncation is seen as the predominant type of change. Analysis points to the following novel aspects: (a) Analysis using data from the manually curated Vega indicates that one in 8.9 genes can lead to a protein isoform of no "known" function; and one in 18 expressed protein isoforms can be such an "orphan" isoform; the corresponding numbers as seen with computationally predicted ASD data set are: one in 4.9 genes and one in 9.8 isoforms. (b) When swapping of signatures occurs, it is often between those of same functional classifications. (c) Pfam domains can occur in varying lengths, and PRINTS fingerprints can occur with varying number of constituent motifs among isoforms – since such a variation is seen in large number of genes, it could be a general mechanism to modulate protein function. (ii) Data: The reported resource (at http://www.bioinformatica.crs4.org/tools/dbs/splivap/) provides the community ability to access data on splice-mediated protein isoforms (with value-added annotation such as association with diseases) through changes in protein signatures.</p
Fragment Prioritization on a Large Mutagenicity Dataset
No full textThe identification of structural alerts is one of the simplest tools used for the identification of potentially toxic chemical compounds. Structural alerts have served as an aid to quickly identify chemicals that should be either prioritized for testing or for elimination from further consideration and use. In the recent years, the availability of larger datasets, often growing in the context of collaborative efforts and competitions, created the raw material needed to identify new and more accurate structural alerts. This work applied a method to efficiently mine large toxicological dataset for structural alert showing a strong statistical association with mutagenicity. In details, we processed a large Ames mutagenicity dataset comprising 14,015 unique molecules obtained by joining different data sources.
After correction for multiple testing, we were able to assign a probability value to each fragment. A total of 51 rules were identified, with p-value < 0.05. Using the same method, we also confirmed the statistical significance of several mutagenicity rules already present and largely recognized in the literature. In addition, we have extended the application of our method by predicting the mutagenicity of an external data set
Peptidomimetics in silico
No full textEndogenous peptides as part of physiological processes are targets of interest when it comes to finding desirable therapeutics which are able to modulate molecular interactions. The major limits presented by peptides when they are used as drugs have motivated the research of the synthesis of peptidomimetics obtained through chemical modification and the use of in silico approaches. Here recent works on the discovery of peptidomimetics by computational methods are reported. Together with molecular dynamic simulations, the use of pharmacophore research simulations helps to gain insight into and understand the molecular determinants underlying the physiological processes
Circular RNAs in Immune-Related Diseases
No full textCircRNAs are a novel class of noncoding RNAs characterized by a covalently closed loop structure lacking both a 3' polyadenylation tail and a 5' cap. Increasing evidence demonstrated that circRNAs can participate in several biological processes including immune system physiology and immune-related diseases. CircRNAs act on immune pathways through several molecular mechanisms including miRNAs and RBP sponges, protein scaffolds, and mRNA stability modulation via diverse signaling pathways including MAPK, JAK-STAT, and Wnt signaling pathway. Recently, circRNAs have also been studied as biomarkers for immune diseases as well as new potential therapeutic targets. Effects of dysregulated circRNA levels correlate, among others, with alterations in immune cell behavior, cytokines production, and immune response in general.In this chapter, we describe new experimental progress in circRNAs that participates in the regulation of the immune system and in the pathogenesis of autoimmune diseases and infectious diseases
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
Support Vector Machine (SVM) as Alternative Tool to Assign Acute Aquatic Toxicity Warning Labels to Chemicals
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