22 research outputs found
MetNet: Software to Build and Model the Biogenetic Lattice of Arabidopsis
MetNet (http://www.botany.iastate.edu/∼mash/metnetex/metabolicnetex.html) is publicly
available software in development for analysis of genome-wide RNA, protein
and metabolite profiling data. The software is designed to enable the biologist to
visualize, statistically analyse and model a metabolic and regulatory network map
of Arabidopsis, combined with gene expression profiling data. It contains a JAVA
interface to an interactions database (MetNetDB) containing information on regulatory
and metabolic interactions derived from a combination of web databases (TAIR,
KEGG, BRENDA) and input from biologists in their area of expertise. FCModeler
captures input from MetNetDB in a graphical form. Sub-networks can be identified
and interpreted using simple fuzzy cognitive maps. FCModeler is intended to develop
and evaluate hypotheses, and provide a modelling framework for assessing the large
amounts of data captured by high-throughput gene expression experiments. FCModeler
and MetNetDB are currently being extended to three-dimensional virtual reality
display. The MetNet map, together with gene expression data, can be viewed using
multivariate graphics tools in GGobi linked with the data analytic tools in R. Users
can highlight different parts of the metabolic network and see the relevant expression
data highlighted in other data plots. Multi-dimensional expression data can be
rotated through different dimensions. Statistical analysis can be computed alongside
the visual. MetNet is designed to provide a framework for the formulation of testable
hypotheses regarding the function of specific genes, and in the long term provide
the basis for identification of metabolic and regulatory networks that control plant
composition and development
Assessment of HAE prophylaxis transition from androgen therapy to berotralstat: A subset analysis of the APeX-S trial
Background: Given the recent approval of oral berotralstat in several countries for hereditary angioedema (HAE) prophylaxis, transition from long-term androgens to berotralstat may occur in clinical practice. The open-label, Phase II APeX-S trial provided an opportunity to assess the safety and effectiveness of berotralstat in patients previously treated with differing durations of androgens and shorter transition periods. Therefore, we examined the safety, effectiveness, and impact on quality of life of berotralstat after prior androgen use in patients from the APeX-S trial. Alanine aminotransferase (ALT) elevations were also examined because of the association with androgen exposure and hepatic function impairment. Methods: We conducted an analysis of a subset of 39 patients from the APeX-S trial aged ≥12 years with HAE due to C1 inhibitor deficiency (HAE-C1-INH) with prior androgen use who discontinued androgen therapy within <60 days of receiving berotralstat. Patients received daily berotralstat (150 mg) and were divided into subgroups for this analysis based on time between androgen discontinuation and berotralstat commencement (<14 days versus 14 to <60 days). Results: Berotralstat was generally well tolerated, with nasopharyngitis (21%), upper respiratory tract infection (15%), nausea (15%), diarrhea (15%), and abdominal pain (10%) being the most common adverse events occurring in ≥10% of the total subset. Only 7/145 (5%) of all APeX-S study patients with a prior history of androgen therapy experienced ALT elevations, 6 of which were grade 3 or 4 toxicities. All 7 patients recovered without sequelae and belonged to the subgroup of patients who transitioned <14 days after discontinuing androgens (n = 18). A reduction in monthly attack rate versus Month 1 was observed over 12 months for all patients who transitioned from prior androgen therapy to berotralstat prophylaxis in under 60 days, irrespective of duration of prior androgen therapy or timing of transition (N = 39). Similarly, meaningful patient-reported improvements from both Angioedema Quality of Life Questionnaire and Treatment Satisfaction Questionnaire for Medication scores were achieved, with a sustained benefit shown over the berotralstat treatment period. Conclusions: Berotralstat treatment led to sustained HAE symptom control irrespective of duration of prior androgen therapy or timing of transition. Most patients safely transitioned from long-term androgens to berotralstat. Although occurring in a small group of patients, liver-related adverse events following berotralstat treatment may be associated with a shorter androgen washout period, but further research is required to confirm this. Clinical trial registration: NCT03472040. Retrospectively registered March 21, 2018