arXiv subjects

Christopher B. Burge

Publications and source records attributed to Christopher B. Burge.

3 recordsLinked to original sources

arXiv2013

Sashimi plots: Quantitative visualization of RNA sequencing read alignments

We introduce Sashimi plots, a quantitative multi-sample visualization of mRNA sequencing reads aligned to gene annotations. Sashimi plots are made using alignments (stored in the SAM/BAM format) and gene model annotations (in GFF format), which can be custom-made by the user or obtained from databases such as Ensembl or UCSC. We describe two implementations of Sashimi plots: (1) a stand-alone command line implementation aimed at making customizable publication quality figures, and (2) an implementation built into the Integrated Genome Viewer (IGV) browser, which enables rapid and dynamic creation of Sashimi plots for any genomic region of interest, suitable for exploratory analysis of alternatively spliced regions of the transcriptome. Isoform expression estimates outputted by the MISO program can be optionally plotted along with Sashimi plots. Sashimi plots can be used to quickly screen differentially spliced exons along genomic regions of interest and can be used in publication quality figures. The Sashimi plot software and documentation is available from: http://genes.mit.edu/burgelab/miso/docs/sashimi.html

q-bio.GN↗

arXiv2004

Untangling influences of hydrophobicity on protein sequences and structures

We fit the Fourier transforms of solvent accessibility and hydrophobicity profiles of a representative set of proteins to a joint multi-variable Gaussian. This allows us to separate the intrinsic tendencies of sequence and structure profiles from the interactions that correlate them; for example, the $α$-helix periodicity in sequence hydrophobicity is dictated by the solvent accessibility of structures. The distinct intrinsic tendencies of sequence and structure profiles are most pronounced at long periods, where sequence hydrophobicity fluctuates more, while solvent accessibility fluctuations are less than average. Interestingly, correlations between the two profiles can be interpreted as the Boltzmann weight of the solvation energy at room temperature.

q-bio.BM↗

arXiv2003

DNA Sequence Evolution with Neighbor-Dependent Mutation

We introduce a model of DNA sequence evolution which can account for biases in mutation rates that depend on the identity of the neighboring bases. An analytic solution for this class of non-equilibrium models is developed by adopting well-known methods of nonlinear dynamics. Results are presented for the CpG-methylation-deamination process which dominates point substitutions in vertebrates. The dinucleotide frequencies generated by the model (using empirically obtained mutation rates) match the overall pattern observed in non-coding DNA. A web-based tool has been constructed to compute single- and dinucleotide frequencies for arbitrary neighbor-dependent mutation rates. Alsoprovided is the backward procedure to infer the mutation rates using maximum likelihood analysis given the observed single- and dinucleotide frequencies. Reasonable estimates of the mutation rates can be obtained very efficiently, using generic non-coding DNA sequences as input, after masking outlong homonucleotide subsequences. Our method is much more convenient and versatile to use than the traditional method of deducing mutation rates by counting mutation events in carefully chosen sequences. More generally, our approach provides a more realistic but still tractable description of non-coding genomic DNA, and may be used as a null model for various sequence analysis applications.

physics.bio-ph↗