Visualizing dimensionality reduction of systems biology data

One of the challenges in analyzing high-dimensional expression data is the detection of important biological signals. A common approach is to apply a dimension reduction method, such as principal component analysis. Typically, after application of such a method the data is projected and visualized in the new coordinate system, using scatter plots or profile plots. These methods provide good results if the data have certain properties which become visible in the new coordinate system and which were hard to detect in the original coordinate system. Often however, the application of only one method does not suffice to capture all important signals. Therefore several methods addressing different aspects of the data need to be applied. We have developed a framework for linear and non-linear dimension reduction methods within our visual analytics pipeline SpRay. This includes measures that assist the interpretation of the factorization result. Different visualizations of these measures can be combined with functional annotations that support the interpretation of the results. We show an application to high-resolution time series microarray data in the antibiotic-producing organism Streptomyces coelicolor as well as to microarray data measuring expression of cells with normal karyotype and cells with trisomies of human chromosomes 13 and 21

Tracking disease resistance deployment in potato breeding by enrichment sequencing

Following the molecular characterisation of functional disease resistance genes in recent years, methods to track and verify the integrity of multiple genes in varieties are needed for crop improvement through resistance stacking. Diagnostic resistance gene enrichment sequencing (dRenSeq) enables the highconfidence identification and complete sequence validation of known functional resistance genes in crops. As demonstrated for tetraploid potato varieties, the methodology is more robust and cost-effective in monitoring resistances than whole-genome sequencing and can be used to appraise (trans)gene integrity efficiently. All currently known NB-LRRs effective against viruses, nematodes and the late blight pathogen Phytophthora infestans can be tracked with dRenSeq in potato and hitherto unknown polymorphisms have been identified. The methodology provides a means to improve the speed and efficiency of future disease resistance breeding in crops by directing parental and progeny selection towards effective combinations of resistance genes

Audio Cartography: Visual Encoding of Acoustic Parameters

Our sonic environment is the matter of subject in multiple domains which developed individual means of its description. As a result, it lacks an established visual language through which knowledge can be connected and insights shared. We provide a visual communication framework for the systematic and coherent documentation of sound in large-scale environments. This consists of visual encodings and mappings of acoustic parameters into distinct graphic variables that present plausible solutions for the visualization of sound. These candidate encodings are assembled into an application-independent, multifunctional, and extensible design guide. We apply the guidelines and show example maps that acts as a basis for the exploration of audio cartography

Microfungi in Drinking Water: The Role of the Frog Litoria caerulea

Microfungi were recovered from all parts of a municipal water distribution system in sub-tropical Australia even though virtually no colony-forming units were recovered from the treated water as it left the treatment plant. A study was then undertaken to determine the potential sources of the microfungal population in the distribution system. Observation of frogs (Litoria caerulea) using the internal infrastructure of a reservoir as diurnal sleeping places, together with observation of visible microfungal growth on their faecal pellets, led to an investigation of the possible involvement of this animal. Old faecal pellets were collected and sporulating fungal colonies growing on their surfaces were identified. Fresh faecal pellets were collected and analysed for microfungal content, and skin swabs were analysed for yeasts. It was found that the faeces and skin of L. caerulea carried large numbers of yeasts as well as spores of various filamentous fungal genera. While there are many possible sources of microfungal contamination of municipal drinking water supplies, this study has revealed that the Australian green tree frog L. caerulea is one of the important sources of filamentous microfungi and yeasts in water storage reservoirs in sub-tropical Australia where the animal is endemic

Use of sonic tomography to detect and quantify wood decay in living trees.

Premise of the studyField methodology and image analysis protocols using acoustic tomography were developed and evaluated as a tool to estimate the amount of internal decay and damage of living trees, with special attention to tropical rainforest trees with irregular trunk shapes.Methods and resultsLiving trunks of a diversity of tree species in tropical rainforests in the Republic of Panama were scanned using an Argus Electronic PiCUS 3 Sonic Tomograph and evaluated for the amount and patterns of internal decay. A protocol using ImageJ analysis software was used to quantify the proportions of intact and compromised wood. The protocols provide replicable estimates of internal decay and cavities for trees of varying shapes, wood density, and bark thickness.ConclusionsSonic tomography, coupled with image analysis, provides an efficient, noninvasive approach to evaluate decay patterns and structural integrity of even irregularly shaped living trees

Patient-reported outcomes in multiple sclerosis: a prospective registry cohort study

Registries have the potential to tackle some of the current limitations in determining the long-term impact of multiple sclerosis. Online assessments using patient-reported outcomes can streamline follow-up enabling large-scale, long-term, cost-effective, home-based, and patient-focused data collection. However, registry data are sparsely sampled and the sensitivity of patient-reported outcomes relative to clinician-reported scales is unknown, making it hard to fully leverage their unique scope and scale to derive insights. This retrospective and prospective cohort study over 11 years involved 15 976 patients with multiple sclerosis from the United Kingdom Multiples Sclerosis Register. Primary outcomes were changes in two patient-reported outcomes: Multiple Sclerosis Impact Scale motor component, and Multiple Sclerosis Walking Scale. First, we investigated their validity in measuring the impact of physical disability in multiple sclerosis, by looking at their sensitivity to disease subtype and duration. We grouped the available records (91 351 for Multiple Sclerosis Impact Scale motor and 68 092 for Multiple Sclerosis Walking Scale) by these two factors, and statistically compared the resulting groups using a novel approach based on Monte Carlo permutation analysis that was designed to cope with the intrinsic sparsity of registry data. Next, we used the patient-reported outcomes to draw novel insights into the developmental time course of subtypes; in particular, the period preceding the transition from relapsing to progressive forms. We report a robust main effect of disease subtype on the patient-reported outcomes and interactions of disease subtype with duration (all P < 0.0001). Specifically, patient-reported outcomes worsen with disease duration for all subtypes (all P < 0.0001) apart from benign multiple sclerosis (Multiple Sclerosis Impact Scale motor: P = 0.796; Multiple Sclerosis Walking Scale: P = 0.983). Furthermore, the patient-reported outcomes of each subtype are statistically different from those of the other subtypes at all time bins (Multiple Sclerosis Impact Scale motor: all P < 0.05; Multiple Sclerosis Walking Scale: all P < 0.01) except when comparing relapsing-remitting multiple sclerosis with benign multiple sclerosis and primary progressive multiple sclerosis with secondary progressive multiple sclerosis. Notably, there were statistically significant differences between relapsing-remitting and progressive subtypes at disease onset. Critically, the patient-reported outcomes are sensitive to future transitions to progressive subtypes, with individuals who transition presenting with higher patient-reported outcomes in their relapsing-remitting phase compared to individuals who don’t transition since onset (all P < 0.0001). Patient-reported outcomes capture different patterns of physical worsening over disease length and across subtypes; therefore, they are a valid tool to measure the physical impact of multiple sclerosis over the long-term and cost-effectively. Furthermore, more advanced physical disability manifests years before clinical detection of progressive subtypes, adding evidence to the presence of a multiple sclerosis prodrome

The impact of smoking cessation on multiple sclerosis disease progression

The negative impact of smoking in MS is well established, however, there is much less evidence as to whether smoking cessation is beneficial to progression in MS. Adults with MS registered on the United Kingdom MS Register (2011-2020) formed this retrospective and prospective cohort study. Primary outcomes were changes in 3 patient reported outcomes (PROs): normalised MS Physical Impact Scale (MSIS-29-Phys), normalised MS Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS-Anxiety and HADS-Depression). Time to event outcomes were clinically significant increases in the PROs. 7983 participants were included, 4130 (51.7%) of these had ever smoked; of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all PROs, current smokers at the time of completing their first questionnaire had higher PRO scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 point for HADS-anxiety and HADS-depression). There was no improvement in PRO scores with increasing time since quitting in former smokers. 923 participants formed the prospective parallel group, which demonstrated that MSIS-29-phy 5.03, [3.71, 6.34], MSWS-12 5.28, [3.62, 6.94] and HADS-depression 0.71, [0.47, 0.96] worsened over a period of 4 years, whereas HADS-anxiety remained stable. Smoking status was significant at year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores (3.05 [0.22, 5.88], 1.14 [0.52,1.76]) while former smokers had a lower MSIS-29 score of -2.91[-5.03, -0.79]. 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all PROs (MSIS-29-Phys: n = 4436, p = 0.0013; MSWS-12: n = 3902, p = 0.0061; HADS-anxiety: n = 4511, p = 0.0017; HADS-depression: n = 4511, p &amp;lt; 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-anxiety and HADS-depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with MS

Measuring quality of life in ALS/MND: validation of the WHOQOL-BREF

Objectives: The World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) is a generic QOL measure with four domains covering Physical, Psychological, Social and Environment. Providing the opportunity to contrast QoL with other conditions, or with population norms, the current study had three aims: 1) can the established domains of the WHOQOL-BREF be validated within a large ALS/MND population; 2) can a total score be validated and 3) can they provide interval level measurement? / Methods: Data were obtained from the Trajectories of Outcomes in Neurological Conditions study. Internal construct validity was determined by fit of the data to the Rasch measurement model. / Results: 636 participants with ALS/MND were included. All domains, except the Social domain, showed satisfactory fit to the Rasch model. All were unidimensional, and showed no Differential Item Functioning by age, gender, or onset type. Finally, a total score was validated from a bi-factor perspective. / Conclusions: The WHOQOL-BREF is valid for use in populations with ALS/MND and can be analyzed to yield interval level measurement: It offers a range of domains that reflect QOL, which can be used for parametric analysis and for comparison with other conditions or general populations, two advantages for its inclusion as a trial outcome measure and for observational studies

Influence of non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) on the pharmacodynamic activity of gliclazide in animal models

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes may occur as a result of HIV infection and/or its treatment. Gliclazide is a widely used drug for the treatment of type 2 diabetes. Efavirenz and nevirapine are widely used non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. The role of Efavirenz and nevirapine on the pharmacodynamic activity of gliclazide is not currently known. The objective of this study was to examine the effect of oral administration of efavirenz and nevirapine on blood glucose and investigate their effect on the activity of gliclazide in rats (normal and diabetic) and rabbits to evaluate the safety and effectiveness of the combination.</p> <p>Methods</p> <p>Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 2 mg/kg bd. wt. of gliclazide, 54 mg/kg bd. wt. of efavirenz or 18 mg/kg bd. wt. of nevirapine and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with 5.6 mg/1.5 kg bd. wt. of gliclazide, 42 mg/1.5 kg bd. wt. of efavirenz or 14 mg/1.5 kg bd. wt. of nevirapine and their combination given orally. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analysed for blood glucose by GOD/POD method.</p> <p>Results</p> <p>Efavirenz and nevirapine alone have no significant effect on the blood glucose level in rats and rabbits. Gliclazide produced hypoglycaemic/antidiabetic activity in normal and diabetic rats with peak activity at 2 h and 8 h and hypoglycaemic activity in normal rabbits at 3 h. In combination, efavirenz reduced the effect of gliclazide in rats and rabbits, and the reduction was more significant with the single dose administration of efavirenz than multiple dose administration. In combination, nevirapine has no effect on the activity of gliclazide in rats and rabbits.</p> <p>Conclusion</p> <p>Thus, it can be concluded that the combination of efavirenz and gliclazide may need dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. The combination of nevirapine and gliclazide was safe. However, further studies are warranted.</p