An automated system for quantitative analysis of Drosophila larval locomotion

Background: Drosophila larvae have been used as a model to study to genetic and cellular circuitries modulating behaviors. One of the challenges in behavioral study is the quantification of complex phenotypes such as locomotive behaviors. Experimental capability can be greatly enhanced by an automatic single-animal tracker that records an animal at a high resolution for an extended period, and analyzes multiple behavioral parameters. Results: Here we present MaggotTracker, a single-animal tracking system for Drosophila larval locomotion analysis. This system controls the motorized microscope stage while taking a video, so that the animal remains in the viewing center. It then reduces the animal to 13 evenly distributed points along the midline, and computes over 20 parameters evaluating the shape, peristalsis movement, stamina, and track of the animal. To demonstrate its utility, we applied MaggotTracker to analyze both wild-type and mutant animals to identify factors affecting locomotive behaviors. Each animal was tracked for four minutes. Our analysis on Canton-S third-instar larvae revealed that the distance an animal travelled was correlated to its striding speed rather than the percentage of time the animal spent striding, and that the striding speed was correlated to both the distance and the duration of one stride. Sexual dimorphism was observed in body length but not in locomotive parameters such as speed. Locomotive parameters were affected by animal developmental stage and the crawling surface. No significant changes in movement speed were detected in mutants of circadian genes such as period (per), timeout, and timeless (tim). The MaggotTracker analysis showed that ether a go-go (eag), Shaker (Sh), slowpoke (slo), and dunce (dnc) mutant larvae had severe phenotypes in multiple locomotive parameters such as stride distance and speed, consistent with their function in neuromuscular junctions. Further, the phenotypic patterns of the K+ channel genes eag, Sh and slo are highly similar. Conclusions: These results showed that MaggotTracker is an efficient tool for automatic phenotyping. The MaggotTracker software as well as the data presented here can be downloaded from our open-access site www.WormLoco.org/Ma

Data Processing in Space, Time, and Semantics Dimensions

This work presents an experimental system for data processing in space, time and semantics dimensions using current Semantic Web technologies. The paper describes how we obtain geographic and event data from Internet sources and also how we integrate them into an RDF store. We briefly introduce a set of functionalities in space, time and semantics dimensions. These functionalities are implemented based on our existing technology for main-memory based RDF data processing developed in the LSDIS Lab. A number of these functionalities are exposed as REST Web services. We present two sample client side applications that are developed using a combination of our services with Google map service

A strategy to apply quantitative epistasis analysis on developmental traits

Abstract Background Genetic interactions are keys to understand complex traits and evolution. Epistasis analysis is an effective method to map genetic interactions. Large-scale quantitative epistasis analysis has been well established for single cells. However, there is a substantial lack of such studies in multicellular organisms and their complex phenotypes such as development. Here we present a method to extend quantitative epistasis analysis to developmental traits. Methods In the nematode Caenorhabditis elegans, we applied RNA interference on mutants to inactivate two genes, used an imaging system to quantitatively measure phenotypes, and developed a set of statistical methods to extract genetic interactions from phenotypic measurement. Results Using two different C. elegans developmental phenotypes, body length and sex ratio, as examples, we showed that this method could accommodate various metazoan phenotypes with performances comparable to those methods in single cell growth studies. Comparing with qualitative observations, this method of quantitative epistasis enabled detection of new interactions involving subtle phenotypes. For example, several sex-ratio genes were found to interact with brc-1 and brd-1, the orthologs of the human breast cancer genes BRCA1 and BARD1, respectively. We confirmed the brc-1 interactions with the following genes in DNA damage response: C34F6.1, him-3 (ortholog of HORMAD1, HORMAD2), sdc-1, and set-2 (ortholog of SETD1A, SETD1B, KMT2C, KMT2D), validating the effectiveness of our method in detecting genetic interactions. Conclusions We developed a reliable, high-throughput method for quantitative epistasis analysis of developmental phenotypes

Context-Aware Semantic Association Ranking

Discovering complex and meaningful relationships, which we call Semantic Associations, is an important challenge. Just as ranking of documents is a critical component of today\u27s search engines, ranking of relationships will be essential in tomorrow\u27s semantic search engines that would support discovery and mining of the Semantic Web. Building upon our recent work on specifying types of Semantic Associations in RDF graphs, which are possible to create through semantic metadata extraction and annotation, we discuss a framework where ranking techniques can be used to identify more interesting and more relevant Semantic Associations. Our techniques utilize alternative ways of specifying the context using ontology. This enables capturing users\u27 interests more precisely and better quality results in relevance ranking

Effect of heuristics on serendipity in path-based storytelling with linked data

Path-based storytelling with Linked Data on the Web provides users the ability to discover concepts in an entertaining and educational way. Given a query context, many state-of-the-art pathfinding approaches aim at telling a story that coincides with the user's expectations by investigating paths over Linked Data on the Web. By taking into account serendipity in storytelling, we aim at improving and tailoring existing approaches towards better fitting user expectations so that users are able to discover interesting knowledge without feeling unsure or even lost in the story facts. To this end, we propose to optimize the link estimation between - and the selection of facts in a story by increasing the consistency and relevancy of links between facts through additional domain delineation and refinement steps. In order to address multiple aspects of serendipity, we propose and investigate combinations of weights and heuristics in paths forming the essential building blocks for each story. Our experimental findings with stories based on DBpedia indicate the improvements when applying the optimized algorithm

Grammar-Based Random Walkers in Semantic Networks

Semantic networks qualify the meaning of an edge relating any two vertices. Determining which vertices are most "central" in a semantic network is difficult because one relationship type may be deemed subjectively more important than another. For this reason, research into semantic network metrics has focused primarily on context-based rankings (i.e. user prescribed contexts). Moreover, many of the current semantic network metrics rank semantic associations (i.e. directed paths between two vertices) and not the vertices themselves. This article presents a framework for calculating semantically meaningful primary eigenvector-based metrics such as eigenvector centrality and PageRank in semantic networks using a modified version of the random walker model of Markov chain analysis. Random walkers, in the context of this article, are constrained by a grammar, where the grammar is a user defined data structure that determines the meaning of the final vertex ranking. The ideas in this article are presented within the context of the Resource Description Framework (RDF) of the Semantic Web initiative.Comment: First draft of manuscript originally written in November 200

Analysis of Neighbourhoods in Multi-layered Dynamic Social Networks

Social networks existing among employees, customers or users of various IT systems have become one of the research areas of growing importance. A social network consists of nodes - social entities and edges linking pairs of nodes. In regular, one-layered social networks, two nodes - i.e. people are connected with a single edge whereas in the multi-layered social networks, there may be many links of different types for a pair of nodes. Nowadays data about people and their interactions, which exists in all social media, provides information about many different types of relationships within one network. Analysing this data one can obtain knowledge not only about the structure and characteristics of the network but also gain understanding about semantic of human relations. Are they direct or not? Do people tend to sustain single or multiple relations with a given person? What types of communication is the most important for them? Answers to these and more questions enable us to draw conclusions about semantic of human interactions. Unfortunately, most of the methods used for social network analysis (SNA) may be applied only to one-layered social networks. Thus, some new structural measures for multi-layered social networks are proposed in the paper, in particular: cross-layer clustering coefficient, cross-layer degree centrality and various versions of multi-layered degree centralities. Authors also investigated the dynamics of multi-layered neighbourhood for five different layers within the social network. The evaluation of the presented concepts on the real-world dataset is presented. The measures proposed in the paper may directly be used to various methods for collective classification, in which nodes are assigned to labels according to their structural input features.Comment: 16 pages, International Journal of Computational Intelligence System

Systematic profiling of Caenorhabditis elegans locomotive behaviors reveals additional components in G-protein Gαq signaling

Genetic screens have been widely applied to uncover genetic mechanisms of movement disorders. However, most screens rely on human observations of qualitative differences. Here we demonstrate the application of an automatic imaging system to conduct a quantitative screen for genes regulating the locomotive behavior in Caenorhabditis elegans. Two hundred twenty-seven neuronal signaling genes with viable homozygous mutants were selected for this study. We tracked and recorded each animal for 4 min and analyzed over 4,400 animals of 239 genotypes to obtain a quantitative, 10-parameter behavioral profile for each genotype. We discovered 87 genes whose inactivation causes movement defects, including 50 genes that had never been associated with locomotive defects. Computational analysis of the high-content behavioral profiles predicted 370 genetic interactions among these genes. Network partition revealed several functional modules regulating locomotive behaviors, including sensory genes that detect environmental conditions, genes that function in multiple types of excitable cells, and genes in the signaling pathway of the G protein Gαq, a protein that is essential for animal life and behavior. We developed quantitative epistasis analysis methods to analyze the locomotive profiles and validated the prediction of the γ isoform of phospholipase C as a component in the Gαq pathway. These results provided a system-level understanding of how neuronal signaling genes coordinate locomotive behaviors. This study also demonstrated the power of quantitative approaches in genetic studies

Differences in transcription between free-living and CO_2-activated third-stage larvae of Haemonchus contortus

Background: The disease caused by Haemonchus contortus, a blood-feeding nematode of small ruminants, is of major economic importance worldwide. The infective third-stage larva (L3) of this gastric nematode is enclosed in a cuticle (sheath) and, once ingested with herbage by the host, undergoes an exsheathment process that marks the transition from the free-living (L3) to the parasitic (xL3) stage. This study explored changes in gene transcription associated with this transition and predicted, based on comparative analysis, functional roles for key transcripts in the metabolic pathways linked to larval development. Results: Totals of 101,305 (L3) and 105,553 (xL3) expressed sequence tags (ESTs) were determined using 454 sequencing technology, and then assembled and annotated; the most abundant transcripts encoded transthyretin-like, calcium-binding EF-hand, NAD(P)-binding and nucleotide-binding proteins as well as homologues of Ancylostoma-secreted proteins (ASPs). Using an in silico-subtractive analysis, 560 and 685 sequences were shown to be uniquely represented in the L3 and xL3 stages, respectively; the transcripts encoded ribosomal proteins, collagens and elongation factors (in L3), and mainly peptidases and other enzymes of amino acid catabolism (in xL3). Caenorhabditis elegans orthologues of transcripts that were uniquely transcribed in each L3 and xL3 were predicted to interact with a total of 535 other genes, all of which were involved in embryonic development. Conclusion: The present study indicated that some key transcriptional alterations taking place during the transition from the L3 to the xL3 stage of H. contortus involve genes predicted to be linked to the development of neuronal tissue (L3 and xL3), formation of the cuticle (L3) and digestion of host haemoglobin (xL3). Future efforts using next-generation sequencing and bioinformatic technologies should provide the efficiency and depth of coverage required for the determination of the complete transcriptomes of different developmental stages and/or tissues of H. contortus as well as the genome of this important parasitic nematode. Such advances should lead to a significantly improved understanding of the molecular biology of H. contortus and, from an applied perspective, to novel methods of intervention

Discovering and Ranking Semantic Associations over a Large RDF Metabase

Information retrieval over semantic metadata has recently received a great amount of interest in both industry and academia. In particular, discovering complex and meaningful relationships among this data is becoming an active research topic. Just as ranking of documents is a critical component of today's search engines, the ranking of relationships will be essential in tomorrow's semantic analytics engines. Building upon our recent work on specifying these semantic relationships, which we refer to as Semantic Associations, we demonstrate a system where these associations are discovered among a large semantic metabase represented in RDF. Additionally we employ ranking techniques to provide users with the most interesting and relevant results