DISA tool: discriminative and informative subspace assessment with categorical and numerical outcomes

Motivation: Pattern discovery and subspace clustering play a central role in the biological domain, supporting for instance putative regulatory module discovery from omic data for both descriptive and predictive ends. In the presence of target variables (e.g. phenotypes), regulatory patterns should further satisfy delineate discriminative power properties, well-established in the presence of categorical outcomes, yet largely disregarded for numerical outcomes, such as risk profiles and quantitative phenotypes. Results: DISA (Discriminative and Informative Subspace Assessment), a Python software package, is proposed to assess patterns in the presence of numerical outcomes using well-established measures together with a novel principle able to statistically assess the correlation gain of the subspace against the overall space. Results confirm the possibility to soundly extend discriminative criteria towards numerical outcomes without the drawbacks well-associated with discretization procedures. A case study is provided to show the properties of the proposed method. Availability: DISA is freely available at https://github.com/JupitersMight/DISA under the MIT license.

Multidisciplinary approach to screening and management of children with Fabry disease: practice at a Tertiary Children’s Hospital in China

Background Fabry disease (FD) remains poorly recognized, especially in children in China. Considering the diversity and nonspecific clinical manifestations accompanying with life-threatening aspect of this disease, methods to improve effective screening and management of the suspects are needed. This study aims to explore how it can be done effectively from a multidisciplinary perspective for children with FD at a tertiary children’s hospital in China. Methods A multidisciplinary team (MDT) of pediatric FD experts was launched at Children’s Hospital of Fudan University. Children with high-risk characteristics were referred by the MDT screening team using the dried blood spot (DBS) triple-test (α-galactosidase A, globotriaosylsphingosine, GLA gene). For newborns who were undergoing genetic testing in the hospital, the GLA gene was listed as a routine analysis gene. Evaluation, family screening, and genetic counselling were implemented after screening by the MDT management team. Results Before the establishment of the MDT, no case was diagnosed with FD in the hospital. However, twelve months following the MDT program's implementation, thirty-five children with high-risk profiles were referred for screening by DBS triple-test, with a yield of diagnosis of 14.3% (5/35). These 5 diagnosed children were referred due to a high-risk profile of pain accompanied by dermatological angiokeratoma and hypohidrosis (n = 2), pain accompanied by abnormal liver function (n = 1), pain only (n = 1), and unexplained renal tubular dysfunction (n = 1). Two neonates were detected early with GLA mutations in the hospital, with a yield of detection of 0.14% (2/1420). Furthermore, another 3 children diagnosed with FD were referred from other hospitals. Family screening of these 10 diagnosed children indicated that 9 boys inherited it from their mothers and 1 girl inherited it from her father. Four of them started to receive enzyme replacement therapy. Conclusion Screening and management of children with FD is effective based on a defined screening protocol and a multidisciplinary approach. We should pay more attention to the high-risk profiles of pain, angiokeratoma, decreased sweating, and unexplained chronic kidney disease in children.

On issues related to national risk-based system for control over food products distributed on the market

This research is vital given great significance of food safety for population and bearing in mind that food products are an independent object of sanitary-epidemiologic control as it is stipulated by the legislation. We suggest approaches to creating a risk-based model for control over food products distributed on the market. These ap-proaches involve categorizing food products as per potential health risks for consumers; building up risk profiles of food products; optimizing laboratory support provided for control and surveillance activities taking into account food products safety management. When categorizing food products, risk is assessed as a combination of probable violation of obligatory requirements to safety and severity of consequences these violations might have. Food products that are assigned into extremely high, high and considerable risk categories are subject to systemic control once a year, every two years or every three years accordingly. In case a surveillance object seems “law-abiding’, its category and intensity of control procedures may be changed. Programs for laboratory control over food products are suggested to be based on risk profiles, spotting out priority indicators that make major contributions into risks. Also the approach involves using mathematical models that describe a relation between a number of observations and an expected answer (as a reduction in quantities of deviating samples at the next stage in the control cycle). This model determines how many samples of priority indicators should be tested in order to achieve a target risk level. It also allows predict an expected number of violations and health risk rates at the next stage in the control cycle given the present number of observations. 85 regional registers of food products were created and categories were determined as per health risks for all groups of food products under surveillance. It was shown that in some cases it was necessary to increase a number of observations over priority (“risky”) indicators in order to detect hazardous products and withdraw them from the market. Certain examinations seem redundant as they don’t play any role in making control procedures more efficient. The suggested approaches are universal and dynamic. Basic trends in the model development may include more targeted selection of products for control; risk profiles creations and systemic actualization; further development of laboratory support for control (surveillance) given that the food products market is changing dynamically in the country.