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- Creators: Biodesign Institute
- Creators: Chou, Ju-hsi
Background:
Many pharmaceutical drugs are known to be ineffective or have negative side effects in a substantial proportion of patients. Genomic advances are revealing that some non-synonymous single nucleotide variants (nsSNVs) may cause differences in drug efficacy and side effects. Therefore, it is desirable to evaluate nsSNVs of interest in their ability to modulate the drug response.
Results:
We found that the available data on the link between drug response and nsSNV is rather modest. There were only 31 distinct drug response-altering (DR-altering) and 43 distinct drug response-neutral (DR-neutral) nsSNVs in the whole Pharmacogenomics Knowledge Base (PharmGKB). However, even with this modest dataset, it was clear that existing bioinformatics tools have difficulties in correctly predicting the known DR-altering and DR-neutral nsSNVs. They exhibited an overall accuracy of less than 50%, which was not better than random diagnosis. We found that the underlying problem is the markedly different evolutionary properties between positions harboring nsSNVs linked to drug responses and those observed for inherited diseases. To solve this problem, we developed a new diagnosis method, Drug-EvoD, which was trained on the evolutionary properties of nsSNVs associated with drug responses in a sparse learning framework. Drug-EvoD achieves a TPR of 84% and a TNR of 53%, with a balanced accuracy of 69%, which improves upon other methods significantly.
Conclusions:
The new tool will enable researchers to computationally identify nsSNVs that may affect drug responses. However, much larger training and testing datasets are needed to develop more reliable and accurate tools.
expenditure, and environmental risk. Surfactant treatment to disrupt Scenedesmus biomass was evaluated
as a means to make solvent extraction more efficient. Surfactant treatment increased the recovery of fatty
acid methyl ester (FAME) by as much as 16-fold vs. untreated biomass using isopropanol extraction, and
nearly 100% FAME recovery was possible without any Folch solvent, which is toxic and expensive. Surfactant
treatment caused cell disruption and morphological changes to the cell membrane, as documented by
transmission electron microscopy and flow cytometry. Surfactant treatment made it possible to extract wet
biomass at room temperature, which avoids the expense and energy cost associated with heating
and drying of biomass during the extraction process. The best FAME recovery was obtained from highlipid
biomass treated with Myristyltrimethylammonium bromide (MTAB)- and 3-(decyldimethylammonio)-
propanesulfonate inner salt (3_DAPS)-surfactants using a mixed solvent (hexane : isopropanol = 1 : 1, v/v)
vortexed for just 1 min; this was as much as 160-fold higher than untreated biomass. The critical micelle
concentration of the surfactants played a major role in dictating extraction performance, but the growth
stage of the biomass had an even larger impact on how well the surfactants disrupted the cells and
improved lipid extraction. Surfactant treatment had minimal impact on extracted-FAME profiles and,
consequently, fuel-feedstock quality. This work shows that surfactant treatment is a promising strategy for
more efficient, sustainable, and economical extraction of fuel feedstock from microalgae.
The Combined Activated Sludge-Anaerobic Digestion Model (CASADM) quantifies the effects of recycling anaerobic-digester (AD) sludge on the performance of a hybrid activated sludge (AS)-AD system. The model includes nitrification, denitrification, hydrolysis, fermentation, methanogenesis, and production/utilization of soluble microbial products and extracellular polymeric substances (EPS). A CASADM example shows that, while effluent COD and N are not changed much by hybrid operation, the hybrid system gives increased methane production in the AD and decreased sludge wasting, both caused mainly by a negative actual solids retention time in the hybrid AD. Increased retention of biomass and EPS allows for more hydrolysis and conversion to methane in the hybrid AD. However, fermenters and methanogens survive in the AS, allowing significant methane production in the settler and thickener of both systems, and AD sludge recycle makes methane formation greater in the hybrid system.