Protein function prediction from dynamic protein interaction network using gene expression data

2019 ◽  
Vol 17 (04) ◽  
pp. 1950025 ◽  
Author(s):  
Sovan Saha ◽  
Abhimanyu Prasad ◽  
Piyali Chatterjee ◽  
Subhadip Basu ◽  
Mita Nasipuri

Computational prediction of functional annotation of proteins is an uphill task. There is an ever increasing gap between functional characterization of protein sequences and deluge of protein sequences generated by large-scale sequencing projects. The dynamic nature of protein interactions is frequently observed which is mostly influenced by any new change of state or change in stimuli. Functional characterization of proteins can be inferred from their interactions with each other, which is dynamic in nature. In this work, we have used a dynamic protein–protein interaction network (PPIN), time course gene expression data and protein sequence information for prediction of functional annotation of proteins. During progression of a particular function, it has also been observed that not all the proteins are active at all time points. For unannotated active proteins, our proposed methodology explores the dynamic PPIN consisting of level-1 and level-2 neighboring proteins at different time points, filtered by Damerau–Levenshtein edit distance to estimate the similarity between two protein sequences and coefficient variation methods to assess the strength of an edge in a network. Finally, from the filtered dynamic PPIN, at each time point, functional annotations of the level-2 proteins are assigned to the unknown and unannotated active proteins through the level-1 neighbor, following a bottom-up strategy. Our proposed methodology achieves an average precision, recall and F-Score of 0.59, 0.76 and 0.61 respectively, which is significantly higher than the reported state-of-the-art methods.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17017-e17017
Author(s):  
Wen Son Hsieh ◽  
Eng Huat Tan ◽  
Wan-Teck Lim ◽  
Ross A. Soo ◽  
Anthony T. C. Chan ◽  
...  

e17017 Background: Epigenetic up-regulation of EBV and cellular genes via demethylation and histone deacetylase inhibition can induce EBV lytic replication enhancing immune mediated tumor killing and up-regulation of tumor suppressor genes resulting in tumor apoptosis. Methods: Patients (Pt) with relapsed or refractory NPC and NK-T cell lymphomas were enrolled to determine safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary anti-tumor activity using a dose escalation design. 5AC was administered on days 1 to 10 sub-cutaneously while SAHA was administered on days 1 to 14 orally. PK for SAHA, EBV viral load, characterization of circulating EBV, Immunohistochemistry (IHC) and EBV promoter methylation analysis in tumor tissue were performed. Results: 11 pt have been treated (M:F 8:3, median age 48, R: 35-71) at 3 dose levels – 5AC 50 mg/m2 and SAHA 200 mg b.i.d. (dose level 1), 5AC 37.5 mg/m2 and SAHA 200 mg q. am and 100 mg q. pm (dose level 2), and 5AC 25 mg/m2 and SAHA 100 mg b.i.d (dose level 3). Median number of previous treatment regimens was 3 (R:1-6). Dose limiting toxicities (DLT) were seen in 2/2 pts at dose level 1: grade 4 thrombocytopenia (1 pt), grade 3 nausea, vomiting and fatigue (2 pts), and grade 5 hepatic failure (1 pt). Two of six patients at dose level 2 experienced DLT: grade 3 fatigue (1 pt) and worsening of pre-existing Sweet’s Syndrome (1 pt). Common AEs (G1/2) included fatigue (73%), cough (64%), anorexia (55%), and injection site reaction (45%). One minor response was seen and 5 pt had prolonged stable disease (>16 weeks), including one patient for 88 weeks. Analysis of post-treatment tumor biopsies showed demethylation of EBV lytic cycle gene promoters after treatment. SAHA PK, IHC results for EBV gene expression in tumor tissue, EBV viral load and characterization of circulating EBV will be presented. Conclusions: 5AC/SAHA appears to be tolerable at dose level 3 with suggestion of clinical benefit. Analysis of post-treatment tumor and blood samples suggests that modulation of EBV gene expression may play a role in the mechanism underlying clinical benefit. Continued accrual at dose level 3 is ongoing. Clinical trial information: NCT00336063.


2018 ◽  
Vol 16 (11) ◽  
pp. 1825-1835 ◽  
Author(s):  
Zixiang Wen ◽  
Ruijuan Tan ◽  
Shichen Zhang ◽  
Paul J. Collins ◽  
Jiazheng Yuan ◽  
...  

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 524
Author(s):  
Bingqi Wu ◽  
Zhiting Chen ◽  
Xiaohui Xu ◽  
Ronghua Chen ◽  
Siwei Wang ◽  
...  

Functional characterization of plant agrichemical transporters provided an opportunity to discover molecules that have a high mobility in plants and have the potential to increase the amount of pesticides reaching damage sites. Agrobacterium-mediated transient expression in tobacco is simple and fast, and its protein expression efficiency is high; this system is generally used to mediate heterologous gene expression. In this article, transient expression of tobacco nicotine uptake permease (NtNUP1) and rice polyamine uptake transporter 1 (OsPUT1) in Nicotiana benthamiana was performed to investigate whether this system is useful as a platform for studying the interactions between plant transporters and pesticides. The results showed that NtNUP1 increases nicotine uptake in N. benthamiana foliar discs and protoplasts, indicating that this transient gene expression system is feasible for studying gene function. Moreover, yeast expression of OsPUT1 apparently increases methomyl uptake. Overall, this method of constructing a transient gene expression system is useful for improving the efficiency of analyzing the functions of plant heterologous transporter-encoding genes and revealed that this system can be further used to study the functions of transporters and pesticides, especially their interactions.


2003 ◽  
Vol 23 (22) ◽  
pp. 8272-8281 ◽  
Author(s):  
Hanna Uvell ◽  
Ylva Engström

ABSTRACT Innate immune reactions are crucial processes of metazoans to protect the organism against overgrowth of faster replicating microorganisms. Drosophila melanogaster is a precious model for genetic and molecular studies of the innate immune system. In response to infection, the concerted action of a battery of antimicrobial peptides ensures efficient killing of the microbes. The induced gene expression relies on translocation of the Drosophila Rel transcription factors Relish, Dif, and Dorsal to the nucleus where they bind to κB-like motifs in the promoters of the inducible genes. We have identified another putative promoter element, called region 1 (R1), in a number of antimicrobial peptide genes. Site-directed mutagenesis of the R1 site diminished Cecropin A1 (CecA1) expression in transgenic Drosophila larvae and flies. Infection of flies induced a nuclear R1-binding activity that was unrelated to the κB-binding activity in the same extracts. Although the R1 motif was required for Rel protein-mediated CecA1 expression in cotransfection experiments, our data argue against it being a direct target for the Drosophila Rel proteins. We propose that the R1 and κB motifs are targets for distinct regulatory complexes that act in concert to promote high levels of antimicrobial peptide gene expression in response to infection.


Sign in / Sign up

Export Citation Format

Share Document