On the hierarchical classification of G Protein-Coupled Receptors

Motivation: G protein-coupled receptors (GPCRs) play an important role in many physiological systems by transducing an extracellular signal into an intracellular response. Over 50% of all marketed drugs are targeted towards a GPCR. There is considerable interest in developing an algorithm that could effectively predict the function of a GPCR from its primary sequence. Such an algorithm is useful not only in identifying novel GPCR sequences but in characterizing the interrelationships between known GPCRs. Results: An alignment-free approach to GPCR classification has been developed using techniques drawn from data mining and proteochemometrics. A dataset of over 8000 sequences was constructed to train the algorithm. This represents one of the largest GPCR datasets currently available. A predictive algorithm was developed based upon the simplest reasonable numerical representation of the protein's physicochemical properties. A selective top-down approach was developed, which used a hierarchical classifier to assign sequences to subdivisions within the GPCR hierarchy. The predictive performance of the algorithm was assessed against several standard data mining classifiers and further validated against Support Vector Machine-based GPCR prediction servers. The selective top-down approach achieves significantly higher accuracy than standard data mining methods in almost all cases

Beyond viral suppression of HIV - the new quality of life frontier

BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV-related discrimination. We propose adding a 'fourth 90' to the testing and treatment target: ensure that 90 % of people with viral load suppression have good health-related quality of life. The new target would expand the continuum-of-services paradigm beyond the existing endpoint of viral suppression. Good health-related quality of life for PLHIV entails attention to two domains: comorbidities and self-perceived quality of life. CONCLUSIONS: Health systems everywhere need to become more integrated and more people-centered to successfully meet the needs of virally suppressed PLHIV. By doing so, these systems can better meet the needs of all of their constituents - regardless of HIV status - in an era when many populations worldwide are living much longer with multiple comorbidities

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

HIV testing among Portuguese men who have sex with men - results from the European MSM Internet Survey (EMIS)

Objectives: To describe HIV testing behaviour and context of MSM in Portugal participating in the European MSM Internet Survey (EMIS). Methods: Data for the Portuguese sample were extracted and those for 5187 participants were analysed. Multivariate logistic regression models were fitted to quantify the association between participants' characteristics and HIV testing behaviour and context. Results: Seventy‐two percent of the participants had ever been tested for HIV and among those ever tested, 11% were diagnosed with HIV. Primary care was the most common testing setting for HIV‐negative men (37%). Compared to those never tested, men who had ever taken an HIV test had higher educational level (aOR 1.89, 95% CI 1.67‐2.14) and identified themselves as gay/homosexual more frequently (aOR 1.94 , 95% CI 1.70‐2.20). HIV testing odds significantly increased with the number of sexual partners in the previous 12 months. Those who reported unprotected anal intercourse (UAI) with a partner of unknown or serodiscordant HIV status in the previous 12 months were less likely to report an HIV test (aOR 0.38, 95% CI 0.33–0.44). Among those never tested or who tested negative, 41% and 22% reported UAI with a partner of unknown or serodiscordant status in the previous 12 months, respectively. Among men with diagnosed HIV, 72% were currently on antiretroviral therapy and 58% reported an undetectable viral load. More than one third (38%) of those who had detectable or unknown/undisclosed viral load reported at least one episode of UAI with a partner of unknown or serodiscordant HIV status in the last 12 months. Conclusions: Actual interventions should focus on: improving testing uptake and counselling; increasing treatment coverage; achieving and maintaining an undetectable viral load; and intensifying prevention efforts focused on consistent condom use

Words, antibodies and their interactions

Jerne’s idiotypic network theory stresses the importance of antibody-to-antibody interactions and provides possible explanations for self-tolerance and increased diversity in the immune repertoire. In this paper, we use an immune network model to build a user profile for adaptive information filtering. Antibody-to-antibody interactions in the profile’s network model correlations between words in text. The user profile has to be able to represent a user’s multiple interests and adapt to changes in them over time. This is a complex and dynamic engineering problem with clear analogies to the immune process of self-assertion. We present a series of experiments investigating the effect of term correlations on the user’s profile performance. The results show that term correlations can encode additional information, which has a positive effect on the profile’s ability to assess the relevance of documents to the user’s interests and to adapt to changes in them