Improved performance and interface with Jmol

Jmol.news.itemThe Affinity Inspector now loads all the protein-DNA and protein-RNA crystal structures from the PDB significantly faster. The improvements in the performance and interface allow users to quickly search through different structures that contain similar proteins from the same protein family or superfamily in order to find the biochemical mechanisms that distinguish differences in specificity. The Needleman-Wunsch global alignment between the amino acid sequences from the crystal structure and affinity model allows users to quickly ascertain how well the crystal structure matches the binding properties of the protein from the binding experiment within different regions of the structure.

Option to display only differential SNP or methylation binding

The Biophysical Browser now has the option to annotate only differential protein-DNA or protein-RNA binding due to annotated SNPs, methylated DNA, or methylated RNA. With this menu option to annotate only differential binding, users can now search for likely functional SNPs within annotated binding sites or possibly functional binding sites that overlap annotated, functional SNPs. With this new functionality, the ADB is a unique resource for searching for functional SNPs and binding sites that drive the differences in gene expression observed in high-throughput transcriptome and proteome data.

Improved rendering and affinity model loading performance

performance.news.itemWe have greatly improved the binding site rendering and affinity model loading performance in the Biophysical Browser. Now, thousands of protein-DNA and protein-RNA affinity models can be loaded into the Biophysical Browser for accurate in vivo binding site annotation. The rendering speed of the annotated binding sites has also greatly improved. Thousands of putative binding sites can now be simultaneously viewed with quick, effortless scale zooming and left-right panning. In addition, relative binding occupancies are now depicted via scaled heights in real-time when protein concentrations are adjusted.

In vivo, DNaseI chromatin accessibility maps now integrated into the Biophysical Browser

dnaseI.map.news.itemDNaseI chromatin accessibility maps from ENCODE are now integrated into the Biophysical Browser. Any of the ENCODE DNaseI data for a particular tissue type can be loaded in the Browser as an affinity-based positional prior that models DNA accessibility. Importantly, these affinity-based positional priors can be included in all the protein-DNA occupancy calculations – which greatly reduces false positive binding predictions in regions of inaccessible DNA.

In vivo protein concentrations inferred from transcriptome or proteome data

protein.concentrations.news.itemThe ADB Biophysical Browser can now infer in vivo transcription factor (TF) and RNA-binding protein (RBP) concentrations from transcriptome or proteome data. The ADB is now unique in its ability to model the biophysical in vivo context of transcriptional and translational gene regulation from RNA-seq data. Specifically, the Biophysical Browser can load transcript or gene-level FPKM, RPKM, or TPM data from GFF2/GTF files, and convert them to maximum occupancies to their highest affinity binding sites.  Protein concentrations are then calculated from these inferred maximum occupancies.

Methylated-RNA affinity models added to the ADB

The ADB now supports methylated-RNA affinity models. These new models can be used by the Biophysical Browser, the Affinity Inspector, and the Comparative Specificity Viewer. The ADB Biophysical Browser is unique in its ability to simultaneously model differences in protein-DNA, protein-methyl-DNA, protein-RNA, and now protein-methyl-RNA binding for each gene isoform due to genetic polymorphisms and/or epigenetic changes. Searching for DNA-binding, protein-methyl-DNA, RNA-binding, and protein-methyl-RNA affinity models is seamlessly integrated into the ADB Model Browser.

Universal Sequence Logos added to the ADB

news.universal-300x109We have added the Universal Sequence Logos Tool to the ADB. This new sequence logo generator produces publication-quality logos that integrate high-order sequence dependencies and corresponded positions for PWMs, PSAMs, Di-PSAMs, and pHMMs. The ADB currently supports DNA, methyl-DNA, and RNA-binding models. It also includes a Correspondence Panel that depicts corresponded columns with tied parameters and shared binding information. The logos also provide biophysical measurements including relative affinities (Kas) and changes in binding free energy (ddG) for each sequence feature.

 

CONTACT

Dr. Todd Riley
Assistant Professor of Biology
University of Massachusetts Boston
100 Morrissey Blvd. | ISC Building Room 4730
Boston, Massachusetts 02125
Phone: (617) 287-3236

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