Supporting cognition in systems biology analysis: findings on users' processes and design implications

Background

Current usability studies of bioinformatics tools suggest that tools for exploratory analysis support some tasks related to finding relationships of interest but not the deep causal insights necessary for formulating plausible and credible hypotheses. To better understand design requirements for gaining these causal insights in systems biology analyses a longitudinal field study of 15 biomedical researchers was conducted. Researchers interacted with the same protein-protein interaction tools to discover possible disease mechanisms for further experimentation.

Results

Findings reveal patterns in scientists' exploratory and explanatory analysis and reveal that tools positively supported a number of well-structured query and analysis tasks. But for several of scientists' more complex, higher order ways of knowing and reasoning the tools did not offer adequate support. Results show that for a better fit with scientists' cognition for exploratory analysis systems biology tools need to better match scientists' processes for validating, for making a transition from classification to model-based reasoning, and for engaging in causal mental modelling.

Conclusion

As the next great frontier in bioinformatics usability, tool designs for exploratory systems biology analysis need to move beyond the successes already achieved in supporting formulaic query and analysis tasks and now reduce current mismatches with several of scientists' higher order analytical practices. The implications of results for tool designs are discussed.

     

Cassava dreg as replacement of corn in goat kid diets

The effects of corn replacement by cassava dreg in diets of crossbred goat kids were evaluated. We tested the impacts of 0, 33, 66 and 100% replacement on intake, digestibility, feeding behaviour, performance and carcass characteristics. Thirty-six goat kids, aged between 4 and 5 months and with initial body weights of 17.61 ± 1.98 kg, were used in a completely randomised design. Analysis of regression revealed a negative linear effect on neutral detergent fibre (NDF) intake and a positive linear effect on non-fibrous carbohydrates (NFC) and hydrocyanic acids (HCN) intake. Cassava dreg use had a positive linear effect on organic matter digestibility and non-fibrous carbohydrates. Based on our results, cassava dreg use did not negatively impact animal performance, feeding behaviour and carcass characteristics, suggesting that it may replace corn up to 100% in the diets of confined goat kids.     

Selection,characterization and genetic analysis of laboratory mutants of <Emphasis Type="Italic">Botryotinia fuckeliana</Emphasis> (<Emphasis Type="Italic">Botrytis cinerea</Emphasis>) resistant to the fungicide boscalid

Resistance to the fungicide boscalid in laboratory mutants of Botryotinia fuckeliana (Botrytis cinerea) was investigated. The baseline sensitivity to boscalid was evaluated in terms of colony growth (EC₅₀ = 0.3–3 μg ml⁻¹; MIC = 10–30 μg ml⁻¹) and conidial germination (EC₅₀ = 0.03–0.1 μg ml⁻¹; MIC = 1–3 μg ml⁻¹) tests. Mutants were selected in vitro from wild-type strains of the fungus on a fungicide-amended medium containing acetate as a carbon source. Mutants showed two different levels of resistance to boscalid, distinguishable through the conidial germination tests: low (EC₅₀ ∼ 0.3 μg ml⁻¹, ranging from 0.03 to 1 μg ml⁻¹; MIC > 100 μg ml⁻¹) and high (EC₅₀ > 100 μg ml⁻¹) resistance. Analysis of meiotic progeny from crosses between resistant mutants and sensitive reference strains showed that resistant phenotypes were due to mutations in single major gene(s) inherited in a Mendelian fashion, and linked with both the Daf1 and Mbc1 genes, responsible for resistance to dicarboximide and benzimidazole fungicides, respectively. Gene sequence analysis of the four sub-units of the boscalid-target protein, the succinate dehydrogenase enzyme, revealed that single or double point mutations in the highly conserved regions of the iron-sulphur protein (Ip) gene were associated with resistance. Mutations resulted in proline to leucine or phenylalanine replacements at position 225 (P225L or P225F) in high resistant mutants, and in a histidine to tyrosine replacement at position 272 (H272Y) in low resistant mutants. Sequences of the flavoprotein and the two transmembrane sub-units of succinate dehydrogenase were never affected.     

Characterisation of the first <Emphasis Type="Italic">Stemphylium vesicarium</Emphasis> isolates resistant to strobilurins in Italian pear orchards

Up to 2005 the sensitivity of Stemphylium vesicarium (Wallr.) Simm., the causal agent of pear brown spot, to the strobilurin fungicides kresoxim-methyl, trifloxystrobin and pyraclostrobin was still comparable with baseline values associated with good efficacy in the field. During 2006, the first resistant isolates were detected in two commercial pear orchards in the Emilia-Romagna region (Italy), one of which was affected by considerable control failure linked to strobilurin treatments as demonstrated in a field trial. In vitro sensitivity tests with 0.5 mg l⁻¹ of kresoxim-methyl, trifloxystrobin and pyraclostrobin showed that in the population collected in the orchard with control failure the conidial germination was greater than 90% compared to an untreated control both in 2006 and in 2007, i.e. 1 year after the suspension of strobilurin applications. In the other orchard, where only a few symptomatic fruits were found and the strobilurins were still in use, the conidial germination was lower, about 50% in 2006 and 25% in 2007. The molecular analysis of mitochondrial cytochrome b gene of some monospore isolates with different levels of sensitivity confirmed the presence of the mutation causing G143A substitution in all the resistant isolates. In conclusion, both in vitro tests and molecular analysis confirmed the first occurrence of Stemphylium vesicarium resistance to all strobilurin fungicides tested.     

Predicting early pregnancy in Egyptian buffalo cows via measuring uterine and luteal blood flows,and serum and saliva progesterone

Various methods are being employed to detect early pregnancy in domestic animals. This study aimed to predict early pregnancy in buffaloes via measuring the corpus luteum (CL) diameter, the luteal blood flow (LBF) area, the uterine blood flow (UBF) vascularization area, and progesterones in saliva and serum for non-pregnant (NPBs, N = 12) and pregnant (PBs, N = 12) buffaloes. The results revealed that the CL diameter and the luteal color blood flow blue and red (P = 0.0001) areas of the pregnant animals kept increasing from day 1 to day 35 of the gestation period, but it decreased in NPBs on day 21 after reaching a peak from ovulation to day 18. Interestingly, the UBF of the pregnant buffaloes (PBs) kept increasing (P = 0.0001) from ovulation to day 42. The difference of the CL diameter (P = 0.03) and the LBF color blue vascularization area (P = 0.002) between PBs and NPBs became clear from day 14 after ovulation, though the difference of UBF between PBs and NPBs became markedly obvious from day 7 after breeding. Both saliva (P = 0.001) and serum (P = 0.0001) progesterones of PBs continued increasing (P = 0.0001) from day 14 to day 35, but those of NPBs started decreasing (P = 0.0001) from day 14 and reached low values on day 21. Therefore, measuring saliva progesterone in addition to the high LBF (day 14) and UBF (day 7) of the pregnant buffaloes using a Doppler ultrasound could be applicable as noninvasive methods to detect early pregnancy and to improve reproductive management of buffaloes.     

The IMPDH inhibitors,ribavirin and mycophenolic acid,inhibit peste des petits ruminants virus infection

Peste des petits ruminants virus (PPRV) causes highly contagious diseases in domestic and particular wild small ruminants, leading to substantial economic loss. The development of effective and cheap antiviral medications shall help to circumvent this emerging burden. In this study, we found that ribavirin, a competitive inosine-5’-monophosphate dehydrogenase (IMPDH) inhibitor, significantly inhibits the replication of PPRV. As IMPDH is a key enzyme in purine nucleotide synthesis, supplementation of exogenous guanosine attenuate the anti-PPRV effect of ribavirin. Interestingly, an uncompetitive IMPDH inhibitor, mycophenolic acid (MPA), exerted more potent antiviral effect again PPRV. Similarly, this effect was largely restored upon supplementation of guanosine. Thus, we have demonstrated that the IMPDH inhibitors ribavirin and MPA combat PPRV infection through purine nucleotide depletion. Because both regimens have been widely used in the clinic for treating viral infection or organ rejection in transplantation patients for decades, respectively, repurposing these existing safe and cheap medications may provide a new avenue for combating PPRV infection.     

The concept of habitat specificity revisited

Habitat specificity indices reflect richness (α) and/or distinctiveness (β) components of diversity. The latter may be defined by α and γ (landscape) diversity in two alternative ways: multiplicatively () and additively (). We demonstrate that the original habitat specificity concept of Wagner and Edwards (Landscape Ecol 16:121–131, 2001) consists of three independent components: core habitat specificity (uniqueness of the species composition), patch area and patch species richness. We describe habitat specificity as a family of indices that may include either area or richness components, or none or both, and open for use of different types of mean in calculation of core habitat specificity. Core habitat specificity is a beta diversity measure: the effective number of completely distinct communities in the landscape. Habitat specificity weighted by species number is a gamma diversity measure: the effective number of species that a patch contributes to landscape richness. We compared 12 habitat specificity indices by theoretical reasoning and by use of field data (vascular plant species in SE Norwegian agricultural landscapes). Habitat specificity indices are strongly influenced by weights for patch area and patch species richness, and the relative contribution of rare vs. common species (type of mean). The relevance of properties emphasized by each habitat specificity index for evaluation of patches in a biodiversity context is discussed. Core habitat specificity is emphasized as an ecologically interpretable measure that specifically addresses patch uniqueness while habitat specificity weighted by species number combines species richness and species composition in ways relevant for conservation biological assessment. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Bird response to disturbance varies with forest productivity in the northwestern United States

Huston’s Dynamic Equilibrium Hypothesis predicts that the response of biodiversity to disturbance varies with productivity. Because disturbance is thought to break competitive advantage of dominant species in productive ecosystems, species richness is predicted to increase with disturbance frequency in productive systems. Recovery of plant biomass following disturbance is also predicted to be faster in productive systems. Here we provide the first test of Huston’s hypothesis in the context of setting harvest rates in managed forests for achieving biodiversity objectives. We examined predictions relating to vegetation and bird response to disturbance and succession in productive and less productive forests in western Oregon and Washington, USA. We found that measurements of understory cover and shrub diversity were higher in young, productive stands than less productive stands of similar age. Later-seral forests in productive environments (mean age = 67 years) had less variable and more complete canopy closure than similar-age forests in less favorable settings. At the stand scale, bird abundance and richness decreased with canopy closure in highly productive forests whereas bird abundance and richness increased with canopy closure in less productive forests. At the landscape scale, bird abundance and richness within stands increased with increasing levels of disturbance in the surrounding landscape within highly productive forests, whereas bird abundance and richness decreased with increasing disturbance in the surrounding landscape within less productive forests. Our results indicate that bird response to disturbance varies across levels of productivity and suggest that bird species abundance and associated species richness will be maximized through relatively more frequent disturbance in highly productive systems.     

Demographic dynamics and off-take of cattle herds in southern Mali

The herds of 95 families were monitored for 1 year in eight villages in the cotton-growing region of southern Mali. In 2006–2007, reproduction performances were average, with 0.54 calvings/year per cow, and mortality was low. Herd numerical productivity is not very high, less than 0.13/year, because of the high proportion of males kept for animal draught. Depending on the herd size, the behaviour of the families differs, in terms of off-take and in-take of animals. Families that only have one or two draught animals seek to increase their animal draught capacity, with a negative net off-take (−0.13/year). Families with two to three cows have a very low net off-take (0.02/year), with culling of adult animals compensated by purchase. They therefore capitalised this year, with an annual herd growth of 8%. Families with a very large herd (20 to 50 cows) take off more of their stock, with a net off-take of 0.08/year (very few animal purchases) and make a stock growth of 5%. And finally, families with an average-sized herd (6 to 19 cows) take off the whole of the year’s production, with a net off-take of 0.11/year and a nil stock growth rate. The use of a demographic model made it possible to measure the sensitivity of the productivity rate to the different demographic parameters.