EMMA： An Efficient Massive Mapping Algorithm Using Improved Approximate Mapping Filtering

Efficient massive mapping algorithm (EMMA),an algorithm on efficiently mapping massivecDNAs onto genomic sequences,has recently been developed.The process of mapping massive cDNAsonto genomic sequences has been improved using more approximate mapping filtering based on an enhancedsuffix array coupled with a pruned fast hash table,algorithms of block alignment extensions,and k-longestpaths.When compared with the classical BLAT software in this field,the computing of EMMA ranges fromtwo to forty-one times faster under similar prediction precisions.     

Topographic Mapping��The Olfactory System

Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils—the olfactory glomeruli—that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.The olfactory system detects airborne organic and inorganic chemicals that originate from plant and animal metabolites and environmental and industrial sources. Odors mediate both innate and learned behaviors such as attraction and aversion, governing decisions to eat, mate, attack or flee from aggressors and predators. A remarkable feature of the olfactory system is the extraordinary diversity of possible odor molecules that exist. Although accurate measurements can be made of the detection range of visual wavelengths or auditory frequencies in humans, there are no reliable estimates of the number of odorous molecules that exist on earth or those that can be detected by a given animal species (Gilbert 2008). Nevertheless, the number of possible odorants is thought to be high, in the range of many thousands. Beyond odor detection lies the problem of odor discrimination: how can chemicals with slightly different physical properties be discriminated and associated with distinct odor percepts?Experiments investigating the molecular logic of olfaction over the last 20 years have led to major insights into how animals solve the problem of detecting and discriminating a vast number of different odor stimuli (Axel 1995). Four organizational principles have emerged from this work. First, large numbers of distinct odorant receptor (OR) genes are dedicated to olfaction: ∼1000 in mammals and ∼100 in insects. Second, each olfactory sensory neuron (OSN) typically expresses only a single receptor out of this large repertoire. Each OR has a distinct odor ligand profile, such that there are ∼1000 types of OSNs in the mouse and ∼100 types in the typical insect. Third, OSNs expressing the same receptor extend axons that converge on the same glomerulus in the brain, forming a map of ORs in the brain. Fourth, each odor is encoded in a combinatorial manner: One odor can activate multiple ORs, and each OR can respond to multiple odors (Malnic et al. 1999; Hallem and Carlson 2006). As a result, odor information is spatially encoded in the first relay station of the brain (reviewed in Mori et al. 2006). Strikingly, these four principles along with the anatomical organization of the olfactory system are quite similar in mammals and insects, suggesting a mechanism of convergent evolution (Hildebrand and Shepherd 1997).Recent studies in two genetic model organisms, the mouse and the fly, Drosophila melanogaster, have elucidated mechanisms governing how the topographic yet discrete olfactory map is established in the brain (see Luo and Flanagan 2007 for an excellent recent review). Although mice and flies have multiple olfactory subsystems and additional classes of chemosensory receptors (reviewed in Brennan and Zufall 2006; Touhara and Vosshall 2009), this article will focus on comparative mechanisms used to map ORs and OSNs from the main olfactory epithelium in the mouse and adult chemosensory structures in the fly to glomerular targets in the brain.     

Deletion Mapping of the λ REX Gene

Deletion mapping has been used to order 12 λ rex^- mutants. Correlation of recombination data with physically-determined positions of deletion end-points (Szybalski 1971; Blattner et al. 1972) suggests that the left-most rex^- mutation, rex209, is located about 260-300 nucleotide pairs from the p_L mutation sex1 and about 475 nucleotide pairs from the left end-point of the region of nonhomology with λimm434.     

Mapping development or how molecular is molecular biology?

The transformation of embryology to developmental biology has been linked to the introduction of experimental approaches from molecular genetics to the study of development. This paper pursues this theme by analyzing the tools molecular biologists, moving from phage and bacterial genetics to the study of development in higher organisms, brought to their new field of investigations. The paper focuses on Sydney Brenner's move from molecular genetics to developmental biology. His attempt to turn the nematode worm Caenorhabditis elegans into a new tool for the study of development included a vast and ever expanding mapping program. Worm workers themselves did not distinguish sharply between mapping on the cellular, chromosomal or molecular level. Mapping, the paper argues, or more generally 'analytical/comparative' next to 'experimentalist' approaches (Pickstone) were not only part and parcel of Brenner's strategy to 'molecularize' the study of development, but also played a crucial role in 'classical' molecular biology.     

Mapping the α-globin genes in HB J Mexico carriers

Summary the organization of the -globin genes was studied by restriction endonuclease mapping, in subjects carrying the variant Hb J Mexico. A subject homozygous for Hb J synthesized both Hb J (about 55%) and Hb A and had two loci per chromosome. His restriction site map was found to be identical to that obtained with a normal DNA, except for a mutant Bgl II site which was observed on the Hb J chromosome proximal to the 5-locus. We have also mapped the DNA of a compound heterozygote for Hb J and -thalassemia, who synthesizes 38% Hb J and we have found a single gene corresponding to a –^3.7 haplotype on one chromosome and two genes, respectively ^J and ^A, on the other.     

Epistasis: Obstacle or Advantage for Mapping Complex Traits?

Identification of genetic loci in complex traits has focused largely on one-dimensional genome scans to search for associations between single markers and the phenotype. There is mounting evidence that locus interactions, or epistasis, are a crucial component of the genetic architecture of biologically relevant traits. However, epistasis is often viewed as a nuisance factor that reduces power for locus detection. Counter to expectations, recent work shows that fitting full models, instead of testing marker main effect and interaction components separately, in exhaustive multi-locus genome scans can have higher power to detect loci when epistasis is present than single-locus scans, and improvement that comes despite a much larger multiple testing alpha-adjustment in such searches. We demonstrate, both theoretically and via simulation, that the expected power to detect loci when fitting full models is often larger when these loci act epistatically than when they act additively. Additionally, we show that the power for single locus detection may be improved in cases of epistasis compared to the additive model. Our exploration of a two step model selection procedure shows that identifying the true model is difficult. However, this difficulty is certainly not exacerbated by the presence of epistasis, on the contrary, in some cases the presence of epistasis can aid in model selection. The impact of allele frequencies on both power and model selection is dramatic.     

Mapping protein–ligand interactions using whole genome phage display libraries

The function of many genes cannot be deduced from sequence similarity, and biochemical methods are usually required. Whole genome sequences can be thought of as not only a set of genes but also collections of functional domains. These domains can be studied by affinity methods whereby identification of the ligand can provide information on biochemical function. To take advantage of this method, one must express all functional domains in a form suitable for affinity studies. Phage display technology provides a means for accomplishing this. The pJuFo phage display system, based on the interaction between the leucine zippers Jun and Fos, has been modified and used to create a genomic phage display library from Escherichia coli MG1655. The system has been tested by using the library to map the dominant binding epitopes for an anti-RecA protein polyclonal antibody sera. This methodology provides a general biochemical approach to functional analysis of protein–ligand interactions on a genome-wide basis.     

SoilGrids1km — Global Soil Information Based on Automated Mapping

BackgroundSoils are widely recognized as a non-renewable natural resource and as biophysical carbon sinks. As such, there is a growing requirement for global soil information. Although several global soil information systems already exist, these tend to suffer from inconsistencies and limited spatial detail.Conclusions/SignificanceSoilGrids1km provide an initial set of examples of soil spatial data for input into global models at a resolution and consistency not previously available. Some of the main limitations of the current version of SoilGrids1km are: (1) weak relationships between soil properties/classes and explanatory variables due to scale mismatches, (2) difficulty to obtain covariates that capture soil forming factors, (3) low sampling density and spatial clustering of soil profile locations. However, as the SoilGrids system is highly automated and flexible, increasingly accurate predictions can be generated as new input data become available. SoilGrids1km are available for download via http://soilgrids.org under a Creative Commons Non Commercial license.     

Mapping the glycoxidation product Nε-carboxymethyllysine in the milk proteome

Milk processing leads to severe protein damage caused by the formation of nonenzymatic posttranslational modifications (nePTMs), such as glycation and glycoxidation. As a result, the technological and nutritional function of milk proteins can be critically altered. The present study investigated the protein-specific distribution of the glycoxidation product N(ε) -carboxymethyllysine (CML) in the proteome of processed milk. For this purpose, raw milk and heated milk were separated by 1-D or 2-DE. The distribution of CML in the milk proteome was examined by immunoblotting. The changes in the protein composition that occurred during heating were monitored by Coomassie staining. Relative modification rates were measured for the major milk protein fractions after 30 and 60 min of heating at 120°C and normalized to the content of the respective protein fraction in the samples. The highest glycoxidation rates were detected in the high molecular weight aggregates that are generated during heating. The casein fraction and the whey protein β-lactoglobulin were affected in a similar manner. The relevance of the results for industrial milk processing was confirmed by analyzing several commercial milk products accordingly. The presented approach allows nonenzymatic posttranslational modification mapping of the entire milk proteome.     

Mapping ApoE/Aβ binding regions to guide inhibitor discovery

Blocking the interaction between the E4 isoform of apolipoprotein E (ApoE) and amyloid beta-peptide (Aβ) may be an avenue for pharmacological intervention in Alzheimer's disease (AD). The main regions of interaction of the two proteins are, respectively, ApoE244-272 and Aβ12-28. These protein segments are too large to facilitate the design of small molecule inhibitors. We mapped the primary components of ApoE/Aβ interaction to smaller peptide segments. Within the three motifs that are primarily responsible for ApoE/Aβ interaction, we identified four peptides that substantially block ApoE/Aβ interaction and further improved their inhibitory activity by rational hydrophobic amino acid substitution. Moreover, the mapping results provide the clue that the Aβ residues which interact with ApoE appear to be in the same region where Aβ self-interacts. According to this information, we found that Congo Red and X-34 could strongly inhibit ApoE/Aβ interaction. Our findings extend our understanding of ApoE/Aβ interaction and may guide the discovery of inhibitors that treat AD by antagonizing ApoE/Aβ interaction.     

Proteomic Profiling of γ-Secretase Substrates and Mapping of Substrate Requirements

The presenilin/γ-secretase complex, an unusual intramembrane aspartyl protease, plays an essential role in cellular signaling and membrane protein turnover. Its ability to liberate numerous intracellular signaling proteins from the membrane and also mediate the secretion of amyloid-β protein (Aβ) has made modulation of γ-secretase activity a therapeutic goal for cancer and Alzheimer disease. Although the proteolysis of the prototypical substrates Notch and β-amyloid precursor protein (APP) has been intensely studied, the full spectrum of substrates and the determinants that make a transmembrane protein a substrate remain unclear. Using an unbiased approach to substrate identification, we surveyed the proteome of a human cell line for targets of γ-secretase and found a relatively small population of new substrates, all of which are type I transmembrane proteins but have diverse biological roles. By comparing these substrates to type I proteins not regulated by γ-secretase, we determined that besides a short ectodomain, γ-secretase requires permissive transmembrane and cytoplasmic domains to bind and cleave its substrates. In addition, we provide evidence for at least two mechanisms that can target a substrate for γ cleavage: one in which a substrate with a short ectodomain is directly cleaved independent of sheddase association, and a second where a substrate requires ectodomain shedding to instruct subsequent γ-secretase processing. These findings expand our understanding of the mechanisms of substrate selection as well as the diverse cellular processes to which γ-secretase contributes.     

Combined Mass Mapping and Biochemical Characterization of Grape β-Glycosidase-enriched Extract

A beta-glucosidase enzyme activity was enriched from skins of ripe grape berry by cell wall fractionation, hydrophobic interaction and cation-exchange chromatographies. This enriched enzyme extract contained several beta-glycosidase activities hydrolyzing a wide range of synthetic and natural monoglycosides and diglycosides, as well as a beta-fructosidase activity. The enzyme extract was further characterized by two-dimensional gel electrophoresis coupled to peptide mass fingerprinting of eight spots using MALDI-TOF mass spectrometry. No beta-glucosidase but a beta-fructosidase associated to the relevant spot at 66 kDa/pI 5.1 was identified. Taken together all results issued from the biochemical characterization, the substrate specificity and the mass spectrometry-based identification of this enriched enzyme extract, we propose that this protein could be a specific beta-fructosidase isoform associated with a broad spectrum of beta-glycosidase activities in grape berry skin and involved in cell wall modifications which occur during the ripening-induced thickness of the grape.     

Mapping DNAase I-susceptible sites in nucleosomes labeled at the 5′ ends

We have used γ-³²P-ATP and polynucleotide kinase to label stoichiometrically the 5′ ends of DNA in intact isolated HeLa cell nucleosomes. DNA is not nicked or degraded during the modification reaction. We have used these modified nucleosomes to study both the distribution and the relative availability of sites within the nucleosome which are susceptible to digestion by DNAase I. The results show that the nucleosome contains a potential cleavage site every 10 nucleotides, with the exception of the site 80 nucleotides from the 5′ end. Favored cleavage sites are located 20, 40, 50, 100, 120, and 130 nucleotides from the 5′ end; sites 30 and 110 nucleotides from the 5′ end are strongly disfavored, while the potential site 80 nucleotides from the 5′ end is virtually never cleaved. These findings provide constraints for models of histone-DNA interactions within the chromatin subunit.     

Mapping and imaging deep-sea coral reefs off Norway, 1982–2000

The survey and mapping group (SMG) of Statoil is responsible for all seafloor mapping for pipelines and field development in Statoil. During numerous reconnaissance and pipeline route surveys over large portions of our contintental shelf, in the North, Norwegian and Barents Seas, we have only detected deep-water coral reefs in a few specific areas. The first reef we found was in 1982, using a combined side scan sonar and sub-bottom profiler system off Fugløy, northern-Norway. Thereafter, numerous reefs were mapped with similar systems off mid-Norway, during the period 1985–1990 for the reconnaissance and final route mapping of the Haltenpipe project. During 1997, we also mapped some previously known reefs in the Trondheimsfjord area while surveying a route for the Tjeldbergodden - Skogn pipeline project. Between 1997 and 2000, we have mapped more reefs along pipeline routes on the outer mid-Norway continental shelf. These reefs are of a smaller size (less than 5 m high) than those mentioned above (5–31 m high). Although side scan sonar and sub-bottom profilers provide a less ambiguous detection of reefs, we have found that modern multi-beam echosounder data can provide adequate remotely sensed data for deep-water coral reef mapping. The interpretation of the reefs is based on visual documentation by ROV (remotely operated vehicle) or by sampling with gravity corers and grabs (ground-truthing). Based on a limited amount of such ground-truthing, it has been possible to extrapolate and use the specific morphological characteristics of the reefs to map their density and distribution. For the Haltenpipe project, we mapped an offshore route corridor of about 200 km length at a width of 3 km with multi-beam echosounder. On the basis of ground-truthing 14 of the suspected coral reefs, we have found the total number of reefs to be 57 within the 600 km² mapped area. All these reefs are higher than 5 m (the highest is 31 m) and of diameters at their base of more than 50 m. Although they occur in local clusters with up to 10 reefs per km², the mean density of reefs along the entire (200 km long) transect is only 0.09 suspected reefs per km². However, there is a large regional density variation, with the highest regional density being 1.2 reefs per km² in an area of subcropping Palaeocene sedimentary rocks. A brief discussion of why the corals have constructed their reefs in the deep, cool, and generally `hostile' waters of the Norwegian continental shelf and fjords concludes with them probably subsisting on a reliable and steady nutrient source, independent of season and variations in the Atlantic Drift (`Gulf stream'). This positive environmental component is called `hydraulically active substrata'. It is thus speculated that micro-organisms, bacteria etc., utilizing the hydraulically activated chemical porewater gradients, cause a local enrichment on which the cnidarian organisms ultimately depend.     

Mapping of the Mouse Actin Capping Protein α Subunit Genes and Pseudogenes

Capping protein (CP), a heterodimer of α and β subunits, is found in all eukaryotes. CP binds to the barbed ends of actin filamentsin vitroand controls actin assembly and cell motilityin vivo.Vertebrates have three α isoforms (α1, α2, α3) produced from different genes, whereas lower organisms have only one gene and one isoform. We isolated genomic clones corresponding to the α subunits of mouse CP and found three α1 genes, two of which are pseudogenes, and a single gene for both α2 and α3. Their chromosomal locations were identified by interspecies backcross mapping. The α1 gene (Cappa1) mapped to Chromosome 3 betweenD3Mit11andD3Mit13.The α1 pseudogenes (Cappa1-ps1andCappa1-ps2) mapped to Chromosomes 1 and 9, respectively. The α2 gene (Cappa2) mapped to Chromosome 6 nearPtn.The α3 gene (Cappa3) also mapped to Chromosome 6, approximately 68 cM distal fromCappa2nearKras2.One mouse mutation,de,maps in the vicinity of the α1 gene. No known mouse mutations map to regions near the α2 or α3 genes.     

Genome-wide Mapping of Cellular Protein–RNA Interactions Enabled by Chemical Crosslinking

RNA–protein interactions influence many biological processes. Identifying the binding sites of RNA-binding proteins（RBPs） remains one of the most fundamental and important challenges to the studies of such interactions. Capturing RNA and RBPs via chemical crosslinking allows stringent purification procedures that significantly remove the non-specific RNA and protein interactions. Two major types of chemical crosslinking strategies have been developed to date, i.e., UV-enabled crosslinking and enzymatic mechanism-based covalent capture. In this review, we compare such strategies and their current applications, with an emphasis on the technologies themselves rather than the biology that has been revealed. We hope such methods could benefit broader audience and also urge for the development of new methods to study RNA RBP interactions.     

Mapping malaria risk in Africa: What can satellite data contribute?

Recent developments in the access of remotely sensed vegetation and weather data, and their analysis along with other data sources within a geographical information system (GIS), have opened up new possibilities for African health services and research institutes in malaria stratification, monitoring and early warning. Madeleine Thomson, Stephen Connor, Paul Milligan and Stephane Flasse review the current situation and outline the way ahead.     

Mapping the Distribution of Anthrax in Mainland China, 2005–2013

BackgroundAnthrax, a global re-emerging zoonotic disease in recent years is enzootic in mainland China. Despite its significance to the public health, spatiotemporal distributions of the disease in human and livestock and its potential driving factors remain poorly understood.Conclusions/SignificanceAnthrax in China was characterized by significant seasonality and spatial clustering. The spatial distribution of human anthrax was largely driven by livestock husbandry, human density, land cover, elevation, topsoil features and climate. Enhanced surveillance and intervention for livestock and human anthrax in the high-risk regions, particularly on the Qinghai-Tibetan Plateau, is the key to the prevention of human infections.