Molecular eco-systems biology: towards an understanding of community function

Systems-biology approaches, which are driven by genome sequencing and high-throughput functional genomics data, are revolutionizing single-cell-organism biology. With the advent of various high-throughput techniques that aim to characterize complete microbial ecosystems (metagenomics, meta-transcriptomics and meta-metabolomics), we propose that the time is ripe to consider molecular systems biology at the ecosystem level (eco-systems biology). Here, we discuss the necessary data types that are required to unite molecular microbiology and ecology to develop an understanding of community function and discuss the potential shortcomings of these approaches

Nonlocal conductance spectroscopy of Andreev bound states: Symmetry relations and BCS charges

Two-terminal conductance spectroscopy of superconducting devices is a common tool for probing Andreev and Majorana bound states. Here, we study theoretically a three-terminal setup, with two normal leads coupled to a grounded superconducting terminal. Using a single-electron scattering matrix, we derive the subgap conductance matrix for the normal leads and discuss its symmetries. In particular, we show that the local and the nonlocal elements of the conductance matrix have pairwise identical antisymmetric components. Moreover, we find that the nonlocal elements are directly related to the local BCS charges of the bound states close to the normal probes and we show how the BCS charge of overlapping Majorana bound states can be extracted from experiments.Comment: 7 page

Identification of attenuation and antitermination regulation in prokaryotes

Many operons of biochemical pathways in bacterial genomes are regulated by processes called attenuation and antitermination. Though the specific mechanism can be quite different, attenuation and antitermination in these operons have in common the termination of transcription by a RNA 'terminator' fold upstream of the first gene in the operon. In the past, detecting regulation by attenuation or antitermination has often been a long process of experimental trial and error, on a case by case basis. We report here the prediction of over 290 upstream regions of genes with attenuation or antitermination regulation structures in the completed genomes of Bacillis subtilis and Escherichia coli for which extensive experimental studies have been done on attenuation and antitermination regulation. These predictions are based on a computational method devised from characteristics of known terminator fold candidates and benchmark regions of entire genomes. We extend this methodology to 24 additional complete genomes and are thus able to give a more complete picture of attenuation and antitermination regulation in bacteria

A novel RNA-binding motif in omnipotent suppressors of translation termination, ribosomal proteins and a ribosome modification enzyme?

Using computer methods for database search, multiple alignment, protein sequence motif analysis and secondary structure prediction, a putative new RNA-binding motif was identified. The novel motif is conserved in yeast omnipotent translation termination suppressor SUP1, the related DOM34 protein and its pseudogene homologue; three groups of eukaryotic and archaeal ribosomal proteins, namely L30e, L7Ae/S6e and S12e; an uncharacterized Bacillus subtilis protein related to the L7A/S6e group; and Escherichia coli ribosomal protein modification enzyme RimK. We hypothesize that a new type of RNA-binding domain may be utilized to deliver additional activities to the ribosome

PTMcode: a database of known and predicted functional associations between post-translational modifications in proteins

Post-translational modifications (PTMs) are involved in the regulation and structural stabilization of eukaryotic proteins. The combination of individual PTM states is a key to modulate cellular functions as became evident in a few well-studied proteins. This combinatorial setting, dubbed the PTM code, has been proposed to be extended to whole proteomes in eukaryotes. Although we are still far from deciphering such a complex language, thousands of protein PTM sites are being mapped by high-throughput technologies, thus providing sufficient data for comparative analysis. PTMcode (http://ptmcode.embl.de) aims to compile known and predicted PTM associations to provide a framework that would enable hypothesis-driven experimental or computational analysis of various scales. In its first release, PTMcode provides PTM functional associations of 13 different PTM types within proteins in 8 eukaryotes. They are based on five evidence channels: a literature survey, residue co-evolution, structural proximity, PTMs at the same residue and location within PTM highly enriched protein regions (hotspots). PTMcode is presented as a protein-based searchable database with an interactive web interface providing the context of the co-regulation of nearly 75 000 residues in >10 000 proteins

Readout and Control of a Power-recycled Interferometric Gravitational-wave Antenna

Interferometric gravitational wave antennas are based on Michelson interferometers whose sensitivity to small differential length changes has been enhanced by adding multiple coupled optical resonators. The use of optical cavities is essential for reaching the required sensitivity, but sets challenges for the control system which must maintain the cavities near resonance. The goal for the strain sensitivity of the Laser Interferometer Gravitational-wave Observatory (LIGO) is 10^-21 rms, integrated over a 100 Hz bandwidth centered at 150 Hz. We present the major design features of the LIGO length and frequency sensing and control system which will hold the differential length to within 5 10^-14 m of the operating point. We also highlight the restrictions imposed by couplings of noise into the gravitational wave readout signal and the required immunity against them.Comment: Presentation at ICALEPCS 2001, San Jose, November 2001, (WECT003), 3 page

RTK: efficient rarefaction analysis of large datasets

Motivation: The rapidly expanding microbiomics field is generating increasingly larger datasets, characterizing the microbiota in diverse environments. Although classical numerical ecology methods provide a robust statistical framework for their analysis, software currently available is inadequate for large datasets and some computationally intensive tasks, like rarefaction and associated analysis. Results: Here we present a software package for rarefaction analysis of large count matrices, as well as estimation and visualization of diversity, richness and evenness. Our software is designed for ease of use, operating at least 7x faster than existing solutions, despite requiring 10x less memory. Availability and implementation: C ++ and R source code (GPL v.2) as well as binaries are available from https://github.com/hildebra/Rarefaction and from CRAN (https://cran.r-project.org/). Contact: [email protected], [email protected]

Functional clues for hypothetical proteins based on genomic context analysis in prokaryotes

Three integrated genomic context methods were used to annotate uncharacterized proteins in 102 bacterial genomes. Of 7853 orthologous groups with unknown function containing 45,110 proteins, 1738 groups could be linked to functionally associated partners. In many cases, those partners are uncharacterized themselves (hinting at newly identified modules) or have been described in general terms only. However, we were able to assign pathways, cellular processes or physical complexes for 273 groups (encompassing 3624 previously functionally uncharacterized proteins)

Update of the G2D tool for prioritization of gene candidates to inherited diseases

G2D (genes to diseases) is a web resource for prioritizing genes as candidates for inherited diseases. It uses three algorithms based on different prioritization strategies. The input to the server is the genomic region where the user is looking for the disease-causing mutation, plus an additional piece of information depending on the algorithm used. This information can either be the disease phenotype (described as an online Mendelian inheritance in man (OMIM) identifier), one or several genes known or suspected to be associated with the disease (defined by their Entrez Gene identifiers), or a second genomic region that has been linked as well to the disease. In the latter case, the tool uses known or predicted interactions between genes in the two regions extracted from the STRING database. The output in every case is an ordered list of candidate genes in the region of interest. For the first two of the three methods, the candidate genes are first retrieved through sequence homology search, then scored accordingly to the corresponding method. This means that some of them will correspond to well-known characterized genes, and others will overlap with predicted genes, thus providing a wider analysis. G2D is publicly available at http://www.ogic.ca/projects/g2d_2

Protein function space: viewing the limits or limited by our view?

Given that the number of protein functions on earth is finite, the rapid expansion of biological knowledge and the concomitant exponential increase in the number of protein sequences should, at some point, enable the estimation of the limits of protein function space. The functional coverage of protein sequences can be investigated using computational methods, especially given the massive amount of data being generated by large-scale environmental sequencing (metagenomics). In completely sequenced genomes, the fraction of proteins to which at least some functional features can be assigned has recently risen to as much as approximately 85%. Although this fraction is more uncertain in metagenomics surveys, because of environmental complexities and differences in analysis protocols, our global knowledge of protein functions still appears to be considerable. However, when we consider protein families, continued sequencing seems to yield an ever-increasing number of novel families. Until we reconcile these two views, the limits of protein space will remain obscured