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

Can Parenting Practices Explain the Differences in Beverage Intake According to Socio-Economic Status

Previous research indicated that preschoolers of lower socioeconomic status (SES) consume less healthy beverages than high SES preschoolers. The purpose of this study is to investigate the mediating role of parenting practices in the relationship between SES and plain water, soft drink and prepacked fruit juice (FJ) consumption in European preschoolers. Parents/caregivers of 3.5 to 5.5 years old (n = 6776) recruited through kindergartens in six European countries within the ToyBox-study completed questionnaires on socio-demographics, parenting practices and a food frequency questionnaire. Availability of sugared beverages and plain water, permissiveness towards sugared beverages and lack of self-efficacy showed a mediating effect on SES-differences in all three beverages. Rewarding with sugared beverages significantly mediated SES-differences for both plain water and prepacked FJ. Encouragement to drink plain water and awareness significantly mediated SES-differences for, respectively, plain water and prepacked FJ consumption. Avoiding negative modelling did not mediate any associations. Overall, lower SES preschoolers were more likely to be confronted with lower levels of favourable and higher levels of unfavourable parenting practices, which may lead to higher sugared beverage and lower plain water consumption. The current study highlights the importance of parenting practices in explaining the relation between SES and both healthy and unhealthy beverage consumptio

Can Parenting Practices Explain the Differences in Beverage Intake According to Socio-Economic Status

Previous research indicated that preschoolers of lower socioeconomic status (SES) consume less healthy beverages than high SES preschoolers. The purpose of this study is to investigate the mediating role of parenting practices in the relationship between SES and plain water, soft drink and prepacked fruit juice (FJ) consumption in European preschoolers. Parents/caregivers of 3.5 to 5.5 years old (n = 6776) recruited through kindergartens in six European countries within the ToyBox-study completed questionnaires on socio-demographics, parenting practices and a food frequency questionnaire. Availability of sugared beverages and plain water, permissiveness towards sugared beverages and lack of self-efficacy showed a mediating effect on SES-differences in all three beverages. Rewarding with sugared beverages significantly mediated SES-differences for both plain water and prepacked FJ. Encouragement to drink plain water and awareness significantly mediated SES-differences for, respectively, plain water and prepacked FJ consumption. Avoiding negative modelling did not mediate any associations. Overall, lower SES preschoolers were more likely to be confronted with lower levels of favourable and higher levels of unfavourable parenting practices, which may lead to higher sugared beverage and lower plain water consumption. The current study highlights the importance of parenting practices in explaining the relation between SES and both healthy and unhealthy beverage consumptio

Multibehavioural Interventions with a Focus on Specific Energy Balance-Related Behaviours Can Affect Diet Quality in Preschoolers from Six European Countries: The ToyBox-Study

The present study aimed to examine whether a multibehavioural intervention with a focus on specific energy balance-related behaviours can affect total diet quality and its four subcomponents in European preschoolers and to investigate if these intervention effects differed by socioeconomic status (SES). Parents/caregivers of 3.5 to 5.5 year-olds (n = 4968) recruited through kindergartens in six European countries within the ToyBox-study completed questionnaires on socio-demographics and a food frequency questionnaire on their preschoolers' diet. To assess intervention effects and differences by SES, multilevel repeated measures analyses were conducted. In contrast to no significant difference in total diet quality, in both the intervention and control group, the dietary quality and dietary equilibrium increased, with a larger increase in the intervention group (mean difference (quality): + 3.4%;mean difference (equilibrium): +0.9%) compared to the control group ((quality): + 1.5%;(equilibrium): + 0.2%). SES was not a significant moderator for intervention effects on total diet quality, nor for the four subcomponents. This study indicates that multibehavioural interventions with a focus on specific energy balance-related behaviours in preschoolers not only affect those targeted behaviours, but can also have more generalized effects. The ToyBox-intervention effects were similar for both lower and high SES preschoolers

Inferring Higher Functional Information for RIKEN Mouse Full-Length cDNA Clones With FACTS

FACTS (Functional Association/Annotation of cDNA Clones from Text/Sequence Sources) is a semiautomated knowledge discovery and annotation system that integrates molecular function information derived from sequence analysis results (sequence inferred) with functional information extracted from text. Text-inferred information was extracted from keyword-based retrievals of MEDLINE abstracts and by matching of gene or protein names to OMIM, BIND, and DIP database entries. Using FACTS, we found that 47.5% of the 60,770 RIKEN mouse cDNA FANTOM2 clone annotations were informative for text searches. MEDLINE queries yielded molecular interaction-containing sentences for 23.1% of the clones. When disease MeSH and GO terms were matched with retrieved abstracts, 22.7% of clones were associated with potential diseases, and 32.5% with GO identifiers. A significant number (23.5%) of disease MeSH-associated clones were also found to have a hereditary disease association (OMIM Morbidmap). Inferred neoplastic and nervous system disease represented 49.6% and 36.0% of disease MeSH-associated clones, respectively. A comparison of sequence-based GO assignments with informative text-based GO assignments revealed that for 78.2% of clones, identical GO assignments were provided for that clone by either method, whereas for 21.8% of clones, the assignments differed. In contrast, for OMIM assignments, only 28.5% of clones had identical sequence-based and text-based OMIM assignments. Sequence, sentence, and term-based functional associations are included in the FACTS database (http://facts.gsc.riken.go.jp/), which permits results to be annotated and explored through web-accessible keyword and sequence search interfaces. The FACTS database will be a critical tool for investigating the functional complexity of the mouse transcriptome, cDNA-inferred interactome (molecular interactions), and pathome (pathologies)

Mediators of the effectiveness of a kindergarten-based, family-involved intervention on pre-schoolers’ snacking behaviour : the ToyBox-study

Objective: The present study aimed to explore the mediating role of family-related determinants on the effects of the ToyBox-intervention on pre-school children's consumption of healthy and unhealthy snacks. Design: The ToyBox-intervention was a kindergarten-based, family-involved intervention with a cluster-randomized design, aiming to promote healthy lifestyle behaviours to prevent obesity at pre-school age. Setting: Kindergartens (n 309) in six European countries. Subjects: A total of 6290 pre-schoolers and their families participated in the ToyBox-intervention in 2012-2013 and data from 5212 pre-schoolers/families were included in the current analyses. Results: Even though the total effect of the ToyBox-intervention on healthy and unhealthy snacking was not significant, the ToyBox-intervention significantly improved parental rule setting on children's unhealthy snack consumption (i.e. restriction of snacking while watching television and permission only at certain occasions) and parental consumption of unhealthy snacks, while it increased parental knowledge on snacking recommendations. Regarding healthy snacking, the ToyBox-intervention improved children's attitude towards fruit and vegetables (F&V). All previously mentioned family-related determinants mediated the intervention effects on pre-schoolers' consumption of healthy and unhealthy snacks. Almost all family-related determinants examined in the study were independently associated with pre-schoolers' consumption of healthy and unhealthy snacks. Conclusions: The intervention was effective in improving relevant family-related determinants. Interventions aiming to promote F&V consumption and limit the consumption of unhealthy snacks in pre-schoolers should target on these mediators, but also identify new family-, school- or peer-related determinants, to enhance their effectiveness

Effect and Process Evaluation of a Cluster Randomized Control Trial on Water Intake and Beverage Consumption in Preschoolers from Six European Countries: The ToyBox-Study

<div><p>Background</p><p>Within the ToyBox-study, a kindergarten-based, family-involved intervention was developed to prevent overweight and obesity in European preschoolers, targeting four key behaviours related to early childhood obesity, including water consumption. The present study aimed to examine the effect of the ToyBox-intervention (cluster randomized controlled trial) on water intake and beverage consumption in European preschoolers and to investigate if the intervention effects differed by implementation score of kindergartens and parents/caregivers.</p><p>Method</p><p>A sample of 4964 preschoolers (4.7±0.4 years; 51.5% boys) from six European countries (Belgium, Bulgaria, Germany, Greece, Poland, Spain) was included in the data analyses. A standardized protocol was used and parents/caregivers filled in socio-demographic data and a food-frequency questionnaire. To assess intervention effects, multilevel repeated measures analyses were conducted for the total sample and for the six country-specific samples. Based on the process evaluation questionnaire of teachers and parents/caregivers, an implementation score was constructed. To assess differences in water intake and beverage consumption by implementation score in the total sample, multilevel repeated measures analyses were performed.</p><p>Results</p><p>Limited intervention effects on water intake from beverages and overall beverage consumption were found. However, important results were found on prepacked fruit juice consumption, with a larger decrease in the intervention group compared to the control group. However, also a decline in plain milk consumption was found. Implementation scores were rather low in both kindergartens and parents/caregivers. Nevertheless, more favorable effects on beverage choices were found in preschoolers whose parents/caregivers and kindergarten teachers had higher implementation scores compared to those with lower implementation scores.</p><p>Conclusion</p><p>The ToyBox-intervention can provide the basis for the development of more tailor-made interventions. However, new strategies to improve implementation of interventions should be created.</p></div