Advanced computing for systems biology

Systems biology is based on computational modelling and simulation of large networks of interacting components. Models may be intended to capture processes, mechanisms, components and interactions at different levels of fidelity. Input data are often large and geographically disperse, and may require the computation to be moved to the data, not vice versa. In addition, complex system-level problems require collaboration across institutions and disciplines. Grid computing can offer robust, scaleable solutions for distributed data, compute and expertise. We illustrate some of the range of computational and data requirements in systems biology with three case studies: one requiring large computation but small data (orthologue mapping in comparative genomics), a second involving complex terabyte data (the Visible Cell project) and a third that is both computationally and data-intensive (simulations at multiple temporal and spatial scales). Authentication, authorisation and audit systems are currently not well scalable and may present bottlenecks for distributed collaboration particularly where outcomes may be commercialised. Challenges remain in providing lightweight standards to facilitate the penetration of robust, scalable grid-type computing into diverse user communities to meet the evolving demands of systems biology.

Linkage mapping of ovine microphthalmia to chromosome 23, the sheep orthologue of human chromosome 18

PURPOSE: To characterize the phenotype and map the locus responsible for autosomal recessive inherited ovine microphthalmia (OMO) in sheep. METHODS: Microphthalmia-affected lambs and their available relatives were collected in a field, and experimental matings were performed to obtain affected and normal lambs for detailed necropsy and histologic examinations. The matings resulted in 18 sheep families with 48 cases of microphthalmia. A comparative candidate gene approach was used to map the disease locus within the sheep genome. Initially, 27 loci responsible for the microphthalmia-anophthalmia phenotypes in humans or mice were selected to test for comparative linkage. Fifty flanking markers that were predicted from comparative genomic analysis to be closely linked to these genes were tested for linkage to the disease locus. After observation of statistical evidence for linkage, a confirmatory fine mapping strategy was applied by further genotyping of 43 microsatellites. RESULTS: The clinical and pathologic examinations showed slightly variable expressivity of isolated bilateral microphthalmia. The anterior eye chamber was small or absent, and a white mass admixed with cystic spaces extended from the papilla to the anterior eye chamber, while no recognizable vitreous body or lens was found within the affected eyes. Significant linkage to a single candidate region was identified at sheep chromosome 23. Fine mapping and haplotype analysis assigned the candidate region to a critical interval of 12.4 cM. This ovine chromosome segment encompasses an ancestral chromosomal breakpoint corresponding to two orthologue segments of human chromosomes 18, short and long arms. For the examined animals, we excluded the complete coding region and adjacent intronic regions of ovine TGIF1 to harbor disease-causing mutations. CONCLUSIONS: This is the first genetic localization for hereditary ovine isolated microphthalmia. It seems unlikely that a mutation in the TGIF1 gene is responsible for this disorder. The studied sheep represent a valuable large animal model for similar human ocular phenotypes.

Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene

Acheiropodia is an autosomal recessive developmental disorder presenting with bilateral congenital amputations of the upper and lower extremities and aplasia of the hands and feet. This severely handicapping condition appears to affect only the extremities, with no other systemic manifestations reported. Recently, a locus for acheiropodia was mapped on chromosome 7q36. Herein we report the narrowing of the critical region for the acheiropodia gene and the subsequent identification of a common mutation in C7orf2-the human orthologue of the mouse Lmbr1 gene-that is responsible for the disease. Analysis of five families with acheiropodia, by means of 15 polymorphic markers, narrowed the critical region to 1.3 cM, on the basis of identity by descent, and to <0.5 Mb, on the basis of physical mapping. Analysis of C7orf2, the human orthologue of the mouse Lmbr1 gene, identified a deletion in all five families, thus identifying a common acheiropodia mutation. The deletion was identified at both the genomic-DNA and mRNA level. It leads to the production of a C7orf2 transcript lacking exon 4 and introduces a premature stop codon downstream of exon 3. Given the nature of the acheiropodia phenotype, it appears likely that the Lmbr1 gene plays an important role in limb development.

Fine mapping of the tomato I-3 gene for fusarium wilt resistance and elimination of a co-segregating resistance gene analogue as a candidate for I-3

The I-3 gene from the wild tomato species Lycopersicon pennellii confers resistance to race 3 of the devastating vascular wilt pathogen Fusarium oxysporum f. sp. lycopersici. As an initial step in a positional cloning strategy for the isolation of I-3, we converted restriction fragment length polymorphism and conserved orthologue set markers, known genes and a resistance gene analogue (RGA) mapping to the I-3 region into PCR-based sequence characterised amplified region (SCAR) and cleaved amplified polymorphic sequence (CAPS) markers. Additional PCR-based markers in the I-3 region were generated using the randomly amplified DNA fingerprinting (RAF) technique. SCAR, CAPS and RAF markers were used for high-resolution mapping around the I-3 locus. The I-3 gene was localised to a 0.3-cM region containing a RAF marker, eO6, and an RGA, RGA332. RGA332 was cloned and found to correspond to a putative pseudogene with at least two loss-of-function mutations. The predicted pseudogene belongs to the Toll interleukin-1 receptor-nucleotide-binding site-leucine-rich-repeat sub-class of plant disease resistance genes. Despite the presence of two RGA332 homologues in L. esculentum, DNA gel blot and PCR analysis suggests that no other homologues are present in lines carrying I-3 that could be alternative candidates for the gene.

The proximal first exon architecture of the murine ghrelin gene is highly similar to its human orthologue

BACKGROUND: The murine ghrelin gene (Ghrl), originally sequenced from stomach tissue, contains five exons and a single transcription start site in a short, 19 bp first exon (exon 0). We recently isolated several novel first exons of the human ghrelin gene and found evidence of a complex transcriptional repertoire. In this report, we examined the 5' exons of the murine ghrelin orthologue in a range of tissues using 5' RACE. -----FINDINGS: 5' RACE revealed two transcription start sites (TSSs) in exon 0 and four TSSs in intron 0, which correspond to 5' extensions of exon 1. Using quantitative, real-time RT-PCR (qRT-PCR), we demonstrated that extended exon 1 containing Ghrl transcripts are largely confined to the spleen, adrenal gland, stomach, and skin. -----CONCLUSION: We demonstrate that multiple transcription start sites are present in exon 0 and an extended exon 1 of the murine ghrelin gene, similar to the proximal first exon organisation of its human orthologue. The identification of several transcription start sites in intron 0 of mouse ghrelin (resulting in an extension of exon 1) raises the possibility that developmental-, cell- and tissue-specific Ghrl mRNA species are created by employing alternative promoters and further studies of the murine ghrelin gene are warranted.

Mapping of indoor environments by robots using low-cost vision sensors

For robots to operate in human environments they must be able to make their own maps because it is unrealistic to expect a user to enter a map into the robot’s memory; existing floorplans are often incorrect; and human environments tend to change. Traditionally robots have used sonar, infra-red or laser range finders to perform the mapping task. Digital cameras have become very cheap in recent years and they have opened up new possibilities as a sensor for robot perception. Any robot that must interact with humans can reasonably be expected to have a camera for tasks such as face recognition, so it makes sense to also use the camera for navigation. Cameras have advantages over other sensors such as colour information (not available with any other sensor), better immunity to noise (compared to sonar), and not being restricted to operating in a plane (like laser range finders). However, there are disadvantages too, with the principal one being the effect of perspective. This research investigated ways to use a single colour camera as a range sensor to guide an autonomous robot and allow it to build a map of its environment, a process referred to as Simultaneous Localization and Mapping (SLAM). An experimental system was built using a robot controlled via a wireless network connection. Using the on-board camera as the only sensor, the robot successfully explored and mapped indoor office environments. The quality of the resulting maps is comparable to those that have been reported in the literature for sonar or infra-red sensors. Although the maps are not as accurate as ones created with a laser range finder, the solution using a camera is significantly cheaper and is more appropriate for toys and early domestic robots.

A new educational technology for media and communication studies : mapping media in Australia and Sweden

This chapter reports on Australian and Swedish experiences in the iterative design, development, and ongoing use of interactive educational systems we call ‘Media Maps.’ Like maps in general, Media Maps are usefully understood as complex cultural technologies; that is, they are not only physical objects, tools and artefacts, but also information creation and distribution technologies, the use and development of which are embedded in systems of knowledge and social meaning. Drawing upon Australian and Swedish experiences with one Media Map technology, this paper illustrates this three-layered approach to the development of media mapping. It shows how media mapping is being used to create authentic learning experiences for students preparing for work in the rapidly evolving media and communication industries. We also contextualise media mapping as a response to various challenges for curriculum and learning design in Media and Communication Studies that arise from shifts in tertiary education policy in a global knowledge economy.

Mapping the regulatory environment : implications for construction firms

As regulators, governments are often criticised for over‐regulating industries. This research project seeks to examine the regulation affecting the construction industry in a federal system of government. It uses a case study of the Australian system of government to focus on the question of the implications of regulation in the construction industry. Having established the extent of the regulatory environment, the research project considers the costs associated with this environment. Consequently, ways in which the regulatory burden on industry can be reduced are evaluated. The Construction Industry Business Environment project is working with industry and government agencies to improve regulatory harmonisation in Australia, and thereby reduce the regulatory burden on industry. It is found that while taxation and compliance costs are not likely to be reduced in the short term, costs arising from having to adapt to variation between regulatory regimes in a federal system of government, seem the most promising way of reducing regulatory costs. Identifying and reducing adaptive costs across jurisdictional are argued to present a novel approach to regulatory reform.

Curriculum mapping of the Spatial Science Program, QUT : what was the cartography journey?

There are currently a number of issues of great importance affecting universities and the way in which their programs are now offered. Many issues are largely being driven top-down and impact both at a university-wide and at an individual discipline level. This paper provides a brief history of cartography and digital mapping education at the Queensland University of Technology (QUT). It also provides an overview of what is curriculum mapping and presents some interesting findings from the program review process. Further, this review process has triggered discussion and action for the review, mapping and embedding of graduate attributes within the spatial science major program. Some form of practical based learning is expected in vocationally oriented degrees that lead to professional accreditation and are generally regarded as a good learning exposure. With the restructure of academic programs across the Faculty of Built Environment and Engineering in 2006, spatial science and surveying students now undertake a formal work integrated learning unit. There is little doubt that students acquire the skills of their discipline (mapping science, spatial) by being immersed in the industry culture- learning how to process information and solve real-world problems within context. The broad theme of where geo-spatial mapping skills are embedded in this broad-based tertiary education course are examined with some focused discussion on the learning objectives, outcomes and examples of some student learning experiences

Mapping the Australian political blogosphere

Network crawling and visualisation tools and other datamining systems are now advanced enough to provide significant new impulses to the study of cultural activity on the Web. A growing range of studies focus on communicative processes in the blogosphere – including for example Adamic & Glance’s 2005 map of political allegiances during the 2004 U.S. presidential election and Kelly & Etling’s 2008 study of blogging practices in Iran. There remain a number of significant shortcomings in the application of such tools and methodologies to the study of blogging; these relate both to how the content of blogs is analysed, and to how the network maps resulting from such studies are understood. Our project highlights and addresses such shortcomings.

Green Marketing Communities and blogs : mapping consumer’s attitudes for future sustainable marketing

The last three decades have seen consumers’ environmental consciousness grow as the environment has moved to a mainstream issue. Results from our study of green marketing blog site comments in the first half of 2009 finds thirteen prominent concepts: carbon, consumers, global and energy were the largest themes, while crisis, power, people, water, fuel, product, work, time, water, organic, content and interest were the others. However sub issues were also identified, as the driving factor of this information is coming from consumer led social networks. While marketers hold some power, consumers are the real key factor to possess influence for change. They want to drive change and importantly, they have the power. Power to the people.

Mapping personal trip OD from probe data

The paper analyses the expected value of OD volumes from probe with fixed error, error that is proportional to zone size and inversely proportional to zone size. To add realism to the analysis, real trip ODs in the Tokyo Metropolitan Region are synthesised. The results show that for small zone coding with average radius of 1.1km, and fixed measurement error of 100m, an accuracy of 70% can be expected. The equivalent accuracy for medium zone coding with average radius of 5km would translate into a fixed error of approximately 300m. As expected small zone coding is more sensitive than medium zone coding as the chances of the probe error envelope falling into adjacent zones are higher. For the same error radii, error proportional to zone size would deliver higher level of accuracy. As over half (54.8%) of the trip ends start or end at zone with equivalent radius of ≤ 1.2 km and only 13% of trips ends occurred at zones with equivalent radius ≥2.5km, measurement error that is proportional to zone size such as mobile phone would deliver higher level of accuracy. The synthesis of real OD with different probe error characteristics have shown that expected value of >85% is difficult to achieve for small zone coding with average radius of 1.1km. For most transport applications, OD matrix at medium zone coding is sufficient for transport management. From this study it can be drawn that GPS with error range between 2 and 5m, and at medium zone coding (average radius of 5km) would provide OD estimates greater than 90% of the expected value. However, for a typical mobile phone operating error range at medium zone coding the expected value would be lower than 85%. This paper assumes transmission of one origin and one destination positions from the probe. However, if multiple positions within the origin and destination zones are transmitted, map matching to transport network could be performed and it would greatly improve the accuracy of the probe data.