Learning Petri net models of non-linear gene interactions

Understanding how an individual's genetic make-up influences their risk of disease is a problem of paramount importance. Although machine-learning techniques are able to uncover the relationships between genotype and disease, the problem of automatically building the best biochemical model or “explanation” of the relationship has received less attention. In this paper, I describe a method based on random hill climbing that automatically builds Petri net models of non-linear (or multi-factorial) disease-causing gene–gene interactions. Petri nets are a suitable formalism for this problem, because they are used to model concurrent, dynamic processes analogous to biochemical reaction networks. I show that this method is routinely able to identify perfect Petri net models for three disease-causing gene–gene interactions recently reported in the literature

Elucidating the phylodynamics of endemic rabies virus in eastern Africa using whole-genome sequencing

Many of the pathogens perceived to pose the greatest risk to humans are viral zoonoses, responsible for a range of emerging and endemic infectious diseases. Phylogeography is a useful tool to understand the processes that give rise to spatial patterns and drive dynamics in virus populations. Increasingly, whole-genome information is being used to uncover these patterns, but the limits of phylogenetic resolution that can be achieved with this are unclear. Here, whole-genome variation was used to uncover fine-scale population structure in endemic canine rabies virus circulating in Tanzania. This is the first whole-genome population study of rabies virus and the first comprehensive phylogenetic analysis of rabies virus in East Africa, providing important insights into rabies transmission in an endemic system. In addition, sub-continental scale patterns of population structure were identified using partial gene data and used to determine population structure at larger spatial scales in Africa. While rabies virus has a defined spatial structure at large scales, increasingly frequent levels of admixture were observed at regional and local levels. Discrete phylogeographic analysis revealed long-distance dispersal within Tanzania, which could be attributed to human-mediated movement, and we found evidence of multiple persistent, co-circulating lineages at a very local scale in a single district, despite on-going mass dog vaccination campaigns. This may reflect the wider endemic circulation of these lineages over several decades alongside increased admixture due to human-mediated introductions. These data indicate that successful rabies control in Tanzania could be established at a national level, since most dispersal appears to be restricted within the confines of country borders but some coordination with neighbouring countries may be required to limit transboundary movements. Evidence of complex patterns of rabies circulation within Tanzania necessitates the use of whole-genome sequencing to delineate finer scale population structure that can that can guide interventions, such as the spatial scale and design of dog vaccination campaigns and dog movement controls to achieve and maintain freedom from disease

Computational Approach to Identifying Universal Macrophage Biomarkers.

Macrophages engulf and digest microbes, cellular debris, and various disease-associated cells throughout the body. Understanding the dynamics of macrophage gene expression is crucial for studying human diseases. As both bulk RNAseq and single cell RNAseq datasets become more numerous and complex, identifying a universal and reliable marker of macrophage cell becomes paramount. Traditional approaches have relied upon tissue specific expression patterns. To identify universal biomarkers of macrophage, we used a previously published computational approach called BECC (Boolean Equivalent Correlated Clusters) that was originally used to identify conserved cell cycle genes. We performed BECC analysis using the known macrophage marker CD14 as a seed gene. The main idea behind BECC is that it uses massive database of public gene expression dataset to establish robust co-expression patterns identified using a combination of correlation, linear regression and Boolean equivalences. Our analysis identified and validated FCER1G and TYROBP as novel universal biomarkers for macrophages in human and mouse tissues

Systematic review of transition models for young people with long-term conditions: A report for NHS Diabetes.

Aims For many young people with Type 1 diabetes, transition from paediatric to adult care can result in a marked deterioration in glycaemic control. A systematic review assessed the effectiveness of transition models, or components of models, for managing the transition process in young people with long-term conditions, including Type 1 diabetes. This involved identifying (i) the main barriers and facilitators in implementing a successful transition programme, and (ii) the key issues for young people with long-term conditions and professionals involved in the transition process. Methods The following databases were searched from inception to August 2012: MEDLINE, EMBASE, PsychINFO, CINAHL, ASSIA, Social Services Abstracts, Academic Search Complete, Social Science Citation Index, Cochrane and Campbell Libraries. Selected studies included young people aged 11 to 25 diagnosed with long-term conditions who were in transition from paediatric to adult secondary health care services. Results 16 systematic reviews and 13 primary studies were included from 9992 records retrieved. No single transition model was uniquely effective. The most successful transitions centred around: young person-focused; age and developmentally appropriate content and delivery; self-management education; family participation; paediatric and adult collaboration; designated transition clinics; transition co-ordinator; young person’s portfolio; specific professionals training; multidisciplinary approach; structured process embedded in service delivery. There were no distinctive characteristics of condition-specific Type 1 diabetes services. Conclusion This important and timely review summarises the key factors that need to be considered for the development of transition programmes for young people with long-term conditions, including those with Type 1 diabetes

The role of the individual in the coming era of process-based therapy

For decades the development of evidence-based therapy has been based on experimental tests of protocols designed to impact psychiatric syndromes. As this paradigm weakens, a more process-based therapy approach is rising in its place, focused on how to best target and change core biopsychosocial processes in specific situations for given goals with given clients. This is an inherently more idiographic question than has normally been at issue in evidence-based therapy over the last few decades. In this article we explore methods of assessment and analysis that can integrate idiographic and nomothetic approaches in a process-based era.Accepted manuscrip

Readiness for Discharge in Parents of Hospitalized Children

Parental preparation for a child\u27s discharge from the hospital sets the stage for successful transitioning to care and recovery at home. In this study of 135 parents of hospitalized children, the quality of discharge teaching, particularly the nurses\u27 skills in “delivery” of parent teaching, was associated with increased parental readiness for discharge, which was associated with less coping difficulty during the first 3 weeks postdischarge. Parental coping difficulty was predictive of greater utilization of posthospitalization health services. These results validate the role of the skilled nurse as a teacher in promoting positive outcomes at discharge and beyond the hospitalization