RCFGL: Rapid Condition adaptive Fused Graphical Lasso and application to modeling brain region co-expression networks

Inferring gene co-expression networks is a useful process for understanding gene regulation and pathway activity. The networks are usually undirected graphs where genes are represented as nodes and an edge represents a significant co-expression relationship. When expression data of multiple (p) genes in multiple (K) conditions (e.g., treatments, tissues, strains) are available, joint estimation of networks harnessing shared information across them can significantly increase the power of analysis. In addition, examining condition-specific patterns of co-expression can provide insights into the underlying cellular processes activated in a particular condition. Condition adaptive fused graphical lasso (CFGL) is an existing method that incorporates condition specificity in a fused graphical lasso (FGL) model for estimating multiple co-expression networks. However, with computational complexity of O(p²K log K), the current implementation of CFGL is prohibitively slow even for a moderate number of genes and can only be used for a maximum of three conditions. In this paper, we propose a faster alternative of CFGL named rapid condition adaptive fused graphical lasso (RCFGL). In RCFGL, we incorporate the condition specificity into another popular model for joint network estimation, known as fused multiple graphical lasso (FMGL). We use a more efficient algorithm in the iterative steps compared to CFGL, enabling faster computation with complexity of O(p²K) and making it easily generalizable for more than three conditions. We also present a novel screening rule to determine if the full network estimation problem can be broken down into estimation of smaller disjoint sub-networks, thereby reducing the complexity further. We demonstrate the computational advantage and superior performance of our method compared to two non-condition adaptive methods, FGL and FMGL, and one condition adaptive method, CFGL in both simulation study and real data analysis. We used RCFGL to jointly estimate the gene co-expression networks in different brain regions (conditions) using a cohort of heterogeneous stock rats. We also provide an accommodating C and Python based package that implements RCFGL.     

Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review

Background

Health-related Quality of Life (HrQoL) is a multidimensional measure, which has gained clinical and social relevance. Implementation of a patient-centred approach to both clinical research and care settings, has increased the recognition of patient and/or observer reported outcome measures (PROMs or ObsROMs) as informative and reliable tools for HrQoL assessment. Inherited Metabolic Diseases (IMDs) are a group of heterogeneous conditions with phenotypes ranging from mild to severe and mostly lacking effective therapies. Consequently, HrQoL evaluation is particularly relevant.

Objectives

We aimed to: (1) identify patient and/or caregiver-reported HrQoL instruments used among IMDs; (2) identify the main results of the application of each HrQoL tool and (3) evaluate the main limitations of HrQoL instruments and study design/methodology in IMDs.

Methods

A scoping review was conducted using methods outlined by Arksey and O’Malley. Additionally, we critically analysed each article to identify the HrQoL study drawbacks.

Results

Of the 1954 studies identified, 131 addressed HrQoL of IMDs patients using PROMs and/or ObsROMs, both in observational or interventional studies. In total, we identified 32 HrQoL instruments destined to self- or proxy-completion; only 2% were disease-specific. Multiple tools (both generic and disease-specific) proved to be responsive to changes in HrQoL; the SF-36 and PedsQL questionnaires were the most frequently used in the adult and pediatric populations, respectively. Furthermore, proxy data often demonstrated to be a reliable approach complementing self-reported HrQoL scores. Nevertheless, numerous limitations were identified especially due to the rarity of these conditions.

Conclusions

HrQoL is still not frequently assessed in IMDs. However, our results show successful examples of the use of patient-reported HrQoL instruments in this field. The importance of HrQoL measurement for clinical research and therapy development, incites to further research in HrQoL PROMs’ and ObsROMs’ creation and validation in IMDs.

     

Survey of aliphatic glucosinolates in Sicilian wild and cultivated Brassicaceae

In the frame of the activities carried out to exploit Sicilian local cultivars of brassicas, we focused our attention on some of the potential health compounds of various local cruciferous crops. These compounds are of interest to improve the quality of the produce with the aim to develop new cultivars capable of providing functional foods able to prevent disease. In this context, we surveyed for the presence of specific glucosinolates in local cultivars of broccoli, cauliflower, kale, and in some wild species widespread in Sicily, using as control various commercial cultivars. Glucosinolate composition varied extensively among species and crops of the same species, such as cauliflower, broccoli and kale. Cultivar variation for glucosinolate profile was also observed for some crops. For example, Sicilian cultivars of cauliflower possessing colored curds displayed a high content of glucosinolates, glucoraphanin in particular, compared to white curd commercial cultivars. Also some wild species had a high content of other glucosinolates.     

Morpho-physiology and maize grain yield under periodic soil flooding in successive selection cycles

This study was carried out to evaluate maize plants of different recurrent selection cycles of the variety (Zea mays L.—Saracura-BRS-4154) regarded to genetic gains, morphophysiology, and grain yield, achieved over the selection cycles under intermittent flooding of the soil. This variety has the capacity to survive and produce in temporarily flooded soils and was developed by the National Maize and Sorghum Research Center (EMBRAPA). The experiment was conducted in greenhouse by using ten alternating selection cycles (Cycle 1–18) and BR 107 a variety known for its susceptibility to flooding. The flooding initiated at six-leaf stage by applying 50 mm of water three times a week. At flowering, the following parameters were evaluated: rate of leaf photosynthesis, stomatal conductance, intercellular CO₂ concentration, transpiration rate, photosynthetically active leaf area, root porosity, relative chlorophyll content, grain yield, harvest index, ear length, and interval between male and female flowering. Yield as a function of root porosity and photosynthesis were also evaluated. An index was created in this study, in order to help the discussion of the characteristics evaluated, it was called “Relative Tolerance Value—RTV”, only gaseous exchange measurements was not included in this index. By the way, it was observed throughout the selection cycles an increase in all gaseous exchange parameters, being the cycle 18, the one which presented the greatest averages. RTV for leaf area showed the greatest values for cycles 7 and 18, whereas root porosity, chlorophyll relative content, and harvest index, the greater RTV values were found in cycles 17 and 18. The largest grain yield RTV was observed in cycle 7, followed by cycles 13, 15, and 18. Flooding resulted in longer Anthesis-Silking Interval, especially for the first cycles. At flooding condition, grain yield was strongly related to root porosity (R ² = 0.66). These results showed that the selection cycles of “Saracura” maize improved some morphophysiologic characters, which favor their survival in flooded environments, also resulting in higher productivity.     

Strain-induced inflammation in pulmonary alveolar tissue due to mechanical ventilation

Inflammation is the body’s attempt at self-protection to remove harmful stimuli, including damaged cells, irritants, or pathogens and begin the healing process. In this study, strain-induced inflammation in pulmonary alveolar tissue under high tidal volume is investigated through a combination of an inflammation model and fluid structure interaction (FSI) analysis. A realistic three-dimensional organ model for alveolar sacs is built, and FSI is employed to evaluate strain distribution in alveolar tissue for different tidal volume (TV) values under the mechanical ventilation (MV) condition. The alveolar tissue is treated as a hyperelastic solid and provides the environment for the tissue constituents. The influence of different strain distributions resulting from different tidal volumes is investigated. It is observed that strain is highly distributed in the inlet area. In addition, strain versus time curves in different locations through the alveolar model reveals that middle layers in the alveolar region would undergo higher levels of strain during breathing under the MV condition. Three different types of strain distributions in the alveolar region from the FSI simulation are transferred to the CA model to study population dynamics of cell constituents under MV for different TVs; 200, 500 and 1000 mL, respectively. The CA model results suggests that strain distribution plays a significant role in population dynamics. An interplay between strain magnitude and distribution appears to influence healing capability. Results suggest that increasing TV leads to an exponential rise in tissue damage by inflammation.     

Isolation and characterization of mannose 6-phosphate/insulin-like growth factor II receptor from bovine serum.

A convenient means was devised for the purification of milligram quantities of a soluble form of the mannose 6-phosphate/insulin-like growth factor II receptor (Man-6-P/IGF II receptor). The receptor was purified to near homogeneity from bovine serum by affinity chromatography on agarose-pentamannosephosphate in the absence of detergent. Approximately 2.5 mg of receptor were obtained from 500 ml of fetal calf serum. The concentration of receptor in serum decreased sharply with development. Fetal calf serum Man-6-P/IGF II receptor was immunologically similar to detergent-solubilized, membrane-bound Man-6-P/IGF II receptor from bovine liver. N-Terminal sequence analysis revealed that the purified serum receptor, but not the solubilized, membrane-associated receptor, contains stoichiometric amounts of bound IGF II. The results of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel chromatography studies suggest that the fetal calf serum receptor (in contrast to the solubilized, membrane-bound bovine testis receptor) does not aggregate. The affinity of the fetal calf serum receptor for bovine testis beta-galactosidase approximated one-half that observed for solubilized, membrane-bound bovine testis receptor.     

<Emphasis Type="Italic">Rubellimicrobium roseum</Emphasis> sp. nov., a Gram-negative bacterium isolated from the forest soil sample

A novel pink-coloured, non-spore-forming, non-motile, Gram-negative bacterium, designated YIM 48858^T, is described by using a polyphasic approach. The strain can grow at pH 6.5–9 (optimum at pH 7) and 25–30°C (optimum at 28°C). NaCl is not required for its growth. Positive for oxidase and catalase. Urease activity, nitrate reduction, starch and Tween 80 tests are negative reaction. 16S rRNA gene sequence similarity studies showed that strain YIM 48858^T is a member of the genus Rubellimicrobium, with similarities of 96.3, 95.7 and 95.5% to Rubellimicrobium mesophilum MSL-20^T, Rubellimicrobium aerolatum 5715S-9^T and Rubellimicrobium thermophilum DSM 16684^T, respectively. Q-10 was the predominant respiratory ubiquinone as in the other members of the genus Rubellimicrobium. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphoglycolipid, glycolipid and the major fatty acids were C18:1 ω7c, C16:0 and C10:0 3-OH, which are very different from the valid published species. The DNA G + C content was 67.7 mol%. Both phylogenetic and chemotaxonomic evidence supports that YIM 48858^T is a novel species of the genus Rubellimicrobium, for which the name Rubellimicrobium roseum sp. nov. is proposed. The type strain is YIM 48858^T (=CCTCC AA 208029^T =KCTC 23202^T).