Selecting Optimal Minimum Spanning Trees that Share a Topological Correspondence with Phylogenetic Trees

Choi et. al (2011) introduced a minimum spanning tree (MST)-based method called CLGrouping, for constructing tree-structured probabilistic graphical models, a statistical framework that is commonly used for inferring phylogenetic trees. While CLGrouping works correctly if there is a unique MST, we observe an indeterminacy in the method in the case that there are multiple MSTs. In this work we remove this indeterminacy by introducing so-called vertex-ranked MSTs. We note that the effectiveness of CLGrouping is inversely related to the number of leaves in the MST. This motivates the problem of finding a vertex-ranked MST with the minimum number of leaves (MLVRMST). We provide a polynomial time algorithm for the MLVRMST problem, and prove its correctness for graphs whose edges are weighted with tree-additive distances

From Large Scale Rearrangements to Mode Coupling Phenomenology

We consider the equilibrium dynamics of Ising spin models with multi-spin interactions on sparse random graphs (Bethe lattices). Such models undergo a mean field glass transition upon increasing the graph connectivity or lowering the temperature. Focusing on the low temperature limit, we identify the large scale rearrangements responsible for the dynamical slowing-down near the transition. We are able to characterize exactly the dynamics near criticality by analyzing the statistical properties of such rearrangements. Our approach can be generalized to a large variety of glassy models on sparse random graphs, ranging from satisfiability to kinetically constrained models.Comment: 4 pages, 4 figures, minor corrections, accepted versio

{BiQ} Analyzer {HiMod}: An Interactive Software Tool for High-throughput Locus-specific Analysis of 5-Methylcytosine and its Oxidized Derivatives

Recent data suggest important biological roles for oxidative modifications of methylated cytosines, specifically hydroxymethylation, formylation and carboxylation. Several assays are now available for profiling these DNA modifications genome-wide as well as in targeted, locus-specific settings. Here we present BiQ Analyzer HiMod, a user-friendly software tool for sequence alignment, quality control and initial analysis of locus-specific DNA modification data. The software supports four different assay types, and it leads the user from raw sequence reads to DNA modification statistics and publication-quality plots. BiQ Analyzer HiMod combines well-established graphical user interface of its predecessor tool, BiQ Analyzer HT, with new and extended analysis modes. BiQ Analyzer HiMod also includes updates of the analysis workspace, an intuitive interface, a custom vector graphics engine and support of additional input and output data formats. The tool is freely available as a stand-alone installation package from http://biq-analyzer-himod.bioinf.mpi-inf.mpg.de/

Association Between {HIV}-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies

Background: Recently discovered broadly neutralizing antibodies have revitalized hopes of developing a universal vaccine against HIV-1. Mainly responsible for new infections are variants only using CCR5 for cell entry, whereas CXCR4-using variants can become dominant in later infection stages. Methods: We performed a statistical analysis on two different previously published data sets. The first data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04, PG9, and PG16. The second data set contained env sequences of viral variants extracted from HIV-1–infected humanized mice treated with the antibody PGT128 and from untreated control mice. Results: For the panel of 199 diverse HIV-1 isolates, we found a statistically significant association between viral resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010, respectively). Our analysis of viral variants from HIV-1–infected humanized mice under treatment with the broadly neutralizing antibody PGT128 indicated that certain antibodies might drive a viral population toward developing CXCR4 coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and control measurement). Conclusions: These analyses highlight the importance of accounting for a possible coreceptor usage bias pertaining to the effectiveness of an HIV vaccine and to passive antibody transfer as therapeutic approach

The origin of human chromosome 2 analyzed by comparative chromosome mapping with a DNA microlibrary

Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata andCercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines

RiffleScrambler - a memory-hard password storing function

We introduce RiffleScrambler: a new family of directed acyclic graphs and a corresponding data-independent memory hard function with password independent memory access. We prove its memory hardness in the random oracle model. RiffleScrambler is similar to Catena -- updates of hashes are determined by a graph (bit-reversal or double-butterfly graph in Catena). The advantage of the RiffleScrambler over Catena is that the underlying graphs are not predefined but are generated per salt, as in Balloon Hashing. Such an approach leads to higher immunity against practical parallel attacks. RiffleScrambler offers better efficiency than Balloon Hashing since the in-degree of the underlying graph is equal to 3 (and is much smaller than in Ballon Hashing). At the same time, because the underlying graph is an instance of a Superconcentrator, our construction achieves the same time-memory trade-offs.Comment: Accepted to ESORICS 201

{DeepBlue} Epigenomic Data Server: {P}rogrammatic Data Retrieval and Analysis of Epigenome Region Sets

Large amounts of epigenomic data are generated under the umbrella of the International Human Epigenome Consortium, which aims to establish 1000 reference epigenomes within the next few years. These data have the potential to unravel the complexity of epigenomic regulation. However, their effective use is hindered by the lack of flexible and easy-to-use methods for data retrieval. Extracting region sets of interest is a cumbersome task that involves several manual steps: identifying the relevant experiments, downloading the corresponding data files and filtering the region sets of interest. Here we present the DeepBlue Epigenomic Data Server, which streamlines epigenomic data analysis as well as software development. DeepBlue provides a comprehensive programmatic interface for finding, selecting, filtering, summarizing and downloading region sets. It contains data from four major epigenome projects, namely ENCODE, ROADMAP, BLUEPRINT and DEEP. DeepBlue comes with a user manual, examples and a well-documented application programming interface (API). The latter is accessed via the XML-RPC protocol supported by many programming languages. To demonstrate usage of the API and to enable convenient data retrieval for non-programmers, we offer an optional web interface. DeepBlue can be openly accessed at http://deepblue.mpi-inf.mpg.de

A strategy for the characterization of minute chromosome rearrangements using multiple color fluorescence in situ hybridization with chromosome-specific DNA libraries and YAC clones

The identification of marker chromosomes in clinical and tumor cytogenetics by chromosome banding analysis can create problems. In this study, we present a strategy to define minute chromosomal rearrangements by multicolor fluorescence in situ hybridization (FISH) with whole chromosome painting probes derived from chromosome-specific DNA libraries and Alu-polymerase chain reaction (PCR) products of various region-specific yeast artificial chromosome (YAC) clones. To demonstrate the usefulness of this strategy for the characterization of chromosome rearrangements unidentifiable by banding techniques, an 8p+ marker chromosome with two extra bands present in the karyotype of a child with multiple anomalies, malformations, and severe mental retardation was investigated. A series of seven-color FISH experiments with sets of fluorochrome-labeled DNA library probes from flow-sorted chromosomes demonstrated that the additional segment on 8p+ was derived from chromosome 6. For a more detailed characterization of the marker chromosome, three-color FISH experiments with library probes specific to chromosomes 6 and 8 were performed in combination with newly established telomeric and subtelomeric YAC clones from 6q25, 6p23, and 8p23. These experiments demonstrated a trisomy 6pter6p22 and a monosomy 8pter8p23 in the patient. The present limitations for a broad application of this strategy and its possible improvements are discusse