1,721,024 research outputs found
Using Secondary Structure Information to Perform Multiple Alignment
No full textIn this paper an approach devised to perform multiple alignment is described, able to exploit any available secondary structure information. In particular, given the sequences to be aligned, their secondary structure (either available or predicted) is used to perform an initial alignment -to be refined by means of locally-scoped operators entrusted with "rearranging" the primary level. Aimed at evaluating both the performance of the technique and the impact of "true" secondary structure information on the quality of alignments, a suitable algorithm has been implemented and assessed on relevant test cases. Experimental results point out that the proposed solution is particularly effective when used to align low similarity protein sequences
FunGenAgent: An Agent-Based Approach for Workflow Composition in Homology Functional Genomics
Full text linkRescuing defective CFTR applying a drug repositioning strategy based on computational studies, surface plasmon resonance and cell-based assays
No full textCystic Fibrosis (CF) is caused by mutations (mainly F508del) of the
cystic fibrosis transmembrane conductance regulator (CFTR). Current
CF therapies are aimed at symptoms alleviation, calling for new
drugs to rescue CFTR function.
Hypothesis and objectives
Drug repositioning is aimed at finding new applications for already
marketed drugs, reducing cost and duration and the likelihood of
unforeseen adverse events. In this project we have integrated drug
repositioning with computational studies, surface plasmon resonance
(SPR) [1] and well-tried cellular models [2] to identify new CF drugs
and to comprehend their mechanism of action.
Methods and results
We have prepared a new structural homology model of intact human
F508del-CFTR embedded in a phospholipid bilayer and a SPR biosensor
containing the same protein in a cell membrane-mimicking lipid
film.
These tools, along with appropriate cell-based assays, have been
firstly used to analyze a mixed library of well-known and new compounds
that allowed the validation of the system and the identification
of a promising molecule endowed with a F508del-binding and
rescuing capacity that is higher than those of drugs already in use.
With the computational model we have then performed a virtual
drug repositioning on a library of 846 drugs, identifying 10 drugs
that were reduced to 4 on the basis of toxicity profile and patient
compliance. These drugs will be now subjected to experimental analysis
by cell-based and SPR assays for their effective capacity to bind
F508del-CFTR and rescue its activity. Also, we will proceed to the virtual
repositioning of a library of natural compounds.
Spin-off for research & clinical purposes
The novel computational models and biosensors will widen the study
of CF drugs and made available to other research groups in the field
of CF.
References
1. Rusnati M, Sala D, Orro A, Bugatti A, Trombetti G, Cichero E, Urbinati C,
Di Somma M, Millo E, Galietta LJV, Milanesi L, Fossa P, D'Ursi P. Speeding
Up the Identification of Cystic Fibrosis Transmembrane Conductance
Regulator-Targeted Drugs: An Approach Based on Bioinformatics Strategies
and Surface Plasmon Resonance. Molecules. 2018 Jan 8;23(1). pii:
E120. doi: 10.3390/molecules23010120.
2. Tomati V, Pesce E, Caci E, Sondo E, Scudieri P, Marini M, Amato F,
Castaldo G, Ravazzolo R, Galietta LJV, Pedemonte N. High-throughput
screening identifies FAU protein as a regulator of mutant cystic fibrosis
transmembrane conductance regulator channel. J Biol Chem. 2018 Jan
26;293(4):1203-1217. doi: 10.1074/jbc.M117.816595. Epub 2017 Nov 20.
Acknowledgment FFC#11/2018 funded by FFC and supported by Delegazione
FFC di Torin
Using a Personalized, Adaptive and Cooperative MultiAgent System to Predict Protein Secondary Structure
No full text
GPU-BSM: A GPU-Based Tool to Map Bisulfite-Treated Reads
No full textCytosine DNA methylation is an epigenetic mark implicated in several biological processes. Bisulfite treatment of DNA is acknowledged as the gold standard technique to study methylation. This technique introduces changes in the genomic DNA by converting cytosines to uracils while 5-methylcytosines remain nonreactive. During PCR amplification 5-methylcytosines are amplified as cytosine, whereas uracils and thymines as thymine. To detect the methylation levels, reads treated with the bisulfite must be aligned against a reference genome. Mapping these reads to a reference genome represents a significant computational challenge mainly due to the increased search space and the loss of information introduced by the treatment. To deal with this computational challenge we devised GPU-BSM, a tool based on modern Graphics Processing Units. Graphics Processing Units are hardware accelerators that are increasingly being used successfully to accelerate general-purpose scientific applications. GPU-BSM is a tool able to map bisulfite-treated reads from whole genome bisulfite sequencing and reduced representation bisulfite sequencing, and to estimate methylation levels, with the goal of detecting methylation. Due to the massive parallelization obtained by exploiting graphics cards, GPU-BSM aligns bisulfite-treated reads faster than other cutting-edge solutions, while outperforming most of them in terms of unique mapped reads
- …
