Identification of "pathologs" (disease-related genes) from the RIKEN mouse cDNA dataset using human curation plus FACTS, a new biological information extraction system

Background: A major goal in the post-genomic era is to identify and characterise disease susceptibility genes and to apply this knowledge to disease prevention and treatment. Rodents and humans have remarkably similar genomes and share closely related biochemical, physiological and pathological pathways. In this work we utilised the latest information on the mouse transcriptome as revealed by the RIKEN FANTOM2 project to identify novel human disease-related candidate genes. We define a new term patholog to mean a homolog of a human disease-related gene encoding a product ( transcript, anti-sense or protein) potentially relevant to disease. Rather than just focus on Mendelian inheritance, we applied the analysis to all potential pathologs regardless of their inheritance pattern. Results: Bioinformatic analysis and human curation of 60,770 RIKEN full-length mouse cDNA clones produced 2,578 sequences that showed similarity ( 70 - 85% identity) to known human-disease genes. Using a newly developed biological information extraction and annotation tool ( FACTS) in parallel with human expert analysis of 17,051 MEDLINE scientific abstracts we identified 182 novel potential pathologs. Of these, 36 were identified by computational tools only, 49 by human expert analysis only and 97 by both methods. These pathologs were related to neoplastic ( 53%), hereditary ( 24%), immunological ( 5%), cardio-vascular (4%), or other (14%), disorders. Conclusions: Large scale genome projects continue to produce a vast amount of data with potential application to the study of human disease. For this potential to be realised we need intelligent strategies for data categorisation and the ability to link sequence data with relevant literature. This paper demonstrates the power of combining human expert annotation with FACTS, a newly developed bioinformatics tool, to identify novel pathologs from within large-scale mouse transcript datasets.

The link between prejudiced attitudes and discriminatory behaviour: The role of ingroup norms

In the present research, a reconceptualisation of the role of norms in the link between prejudiced attitudes and discriminatory behaviour — along the lines suggested by the social identity perspective — was tested. In the first study, group salience and group norm were manipulated. As expected, participants ascribed negative traits to significantly fewer Asian university students when they had received consensus information along these lines from a salient ingroup rather than from a salient outgroup. These results were replicated on a measure of strength of motivation to appear nonprejudiced. In a second study, group salience and norm were once again manipulated and strength of attitude and perceived group threat were measured. As predicted, people's negative attitudes towards globalisation were more likely to predict congruent behavioural responses to the extent that the group norm supported the attitude and group salience was high, particularly when high levels of group threat were perceived.

On-line writing: a link to learning in a teacher education program

This paper examines the use of on-line discussion as a medium for learning in a pre-service teacher education program. As part of an Education Studies course student teachers engaged in a discussion of issues related to technology and equity in schools. The design of the task and the subsequent analysis of the on-line text were part of a research project investigating whether and how communications technology can be used to integrate and extend the learning of teacher education students. The main argument developed in the paper is that through the on-line activity distinctive sets of writing practices were created. These practices enabled students to make connections between the often disparate parts of teacher education programs-theory and practice, campus and school, research and experience. (C) 2002 Elsevier Science Ltd. All rights reserved.

Columnar cell lesions of the breast: The missing link in breast cancer progression? A morphological and molecular analysis

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER an PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma. Copyright: © 2005 Lippincott Williams & Wilkins, Inc.

Trait physiology and crop modelling as a framework to link phenotypic complexity to underlying genetic systems

New tools derived from advances in molecular biology have not been widely adopted in plant breeding for complex traits because of the inability to connect information at gene level to the phenotype in a manner that is useful for selection. In this study, we explored whether physiological dissection and integrative modelling of complex traits could link phenotype complexity to underlying genetic systems in a way that enhanced the power of molecular breeding strategies. A crop and breeding system simulation study on sorghum, which involved variation in 4 key adaptive traits-phenology, osmotic adjustment, transpiration efficiency, stay-green-and a broad range of production environments in north-eastern Australia, was used. The full matrix of simulated phenotypes, which consisted of 547 location-season combinations and 4235 genotypic expression states, was analysed for genetic and environmental effects. The analysis was conducted in stages assuming gradually increased understanding of gene-to-phenotype relationships, which would arise from physiological dissection and modelling. It was found that environmental characterisation and physiological knowledge helped to explain and unravel gene and environment context dependencies in the data. Based on the analyses of gene effects, a range of marker-assisted selection breeding strategies was simulated. It was shown that the inclusion of knowledge resulting from trait physiology and modelling generated an enhanced rate of yield advance over cycles of selection. This occurred because the knowledge associated with component trait physiology and extrapolation to the target population of environments by modelling removed confounding effects associated with environment and gene context dependencies for the markers used. Developing and implementing this gene-to-phenotype capability in crop improvement requires enhanced attention to phenotyping, ecophysiological modelling, and validation studies to test the stability of candidate genetic regions.

Trait physiology and crop modelling to link phenotypic complexity to underlying genetic systems

New tools derived from advances in molecular biology have not been widely adopted in plant breeding because of the inability to connect information at gene level to the phenotype in a manner that is useful for selection. We explore whether a crop growth and development modelling framework can link phenotype complexity to underlying genetic systems in a way that strengthens molecular breeding strategies. We use gene-to-phenotype simulation studies on sorghum to consider the value to marker-assisted selection of intrinsically stable QTLs that might be generated by physiological dissection of complex traits. The consequences on grain yield of genetic variation in four key adaptive traits – phenology, osmotic adjustment, transpiration efficiency, and staygreen – were simulated for a diverse set of environments by placing the known extent of genetic variation in the context of the physiological determinants framework of a crop growth and development model. It was assumed that the three to five genes associated with each trait, had two alleles per locus acting in an additive manner. The effects on average simulated yield, generated by differing combinations of positive alleles for the traits incorporated, varied with environment type. The full matrix of simulated phenotypes, which consisted of 547 location-season combinations and 4235 genotypic expression states, was analysed for genetic and environmental effects. The analysis was conducted in stages with gradually increased understanding of gene-to-phenotype relationships, which would arise from physiological dissection and modelling. It was found that environmental characterisation and physiological knowledge helped to explain and unravel gene and environment context dependencies. We simulated a marker-assisted selection (MAS) breeding strategy based on the analyses of gene effects. When marker scores were allocated based on the contribution of gene effects to yield in a single environment, there was a wide divergence in rate of yield gain over all environments with breeding cycle depending on the environment chosen for the QTL analysis. It was suggested that knowledge resulting from trait physiology and modelling would overcome this dependency by identifying stable QTLs. The improved predictive power would increase the utility of the QTLs in MAS. Developing and implementing this gene-to-phenotype capability in crop improvement requires enhanced attention to phenotyping, ecophysiological modelling, and validation studies to test the stability of candidate QTLs.

Expertise and the perception of kinematic and situational probability information

Two experiments were conducted on the nature of expert perception in the sport of squash. In the first experiment, ten expert and fifteen novice players attempted to predict the direction and force of squash strokes from either a film display (occluded at variable time periods before and after the opposing player had struck the ball) or a matched point-light display (containing only the basic kinematic features of the opponent's movement pattern). Experts outperformed the novices under both display conditions, and the same basic time windows that characterised expert and novice pick-up of information in the film task also persisted in the point-light task. This suggests that the experts' perceptual advantage is directly related to their superior pick-up of essential kinematic information. In the second experiment, the vision of six expert and six less skilled players was occluded by remotely triggered liquid-crystal spectacles at quasi-random intervals during simulated match play. Players were required to complete their current stroke even when the display was occluded and their prediction performance was assessed with respect to whether they moved to the correct half of the court to match the direction and depth of the opponent's stroke. Consistent with experiment 1, experts were found to be superior in their advance pick-up of both directional and depth information when the display was occluded during the opponent's hitting action. However, experts also remained better than chance, and clearly superior to less skilled players, in their prediction performance under conditions where occlusion occurred before any significant pre-contact preparatory movement by the opposing player was visible. This additional source of expert superiority is attributable to their superior attunement to the information contained in the situational probabilities and sequential dependences within their opponent's pattern of play.

Expo 1988 Information Service Centre, Brisbane

View to service centre during Expo 1988.

Religious Information Poverty in Australian State Schools

This paper introduces the concept of religious information poverty in Australian state schools from an information science perspective. Information scientists have been theorising about the global information society for some time, along with its increased provision of vital information for the good of the world. Australian state schools see themselves as preparing children for effective participation in the information society, yet Australian children are currently suffering a religious illiteracy that undermines this goal. Some reasons and theories are offered to explain the existence of religious information poverty in state schools, and suggestions for professional stakeholders are offered for its alleviation.