This page navigates through the documentation about how to use related questions of this webserver.
You are requested to go through both of these sections.


(I) Frequently Asked Questions

(II) How To Use
(I) Frequently Asked Questions
Q. What is TOXsiRNA?

TOXsiRNA is a first prediction pipeline as web server, primarily designed for predicting the toxicity of the chemically modified siRNAs with top twenty one chemical modifications and four natural nucleotides.


Q. What is the need and importance of TOXsiRNA web server?

The SiRNAs are used in most of the labs especially as a molecular tool in functional genomics as well as in therpeutics development {with latest candidateONPATTRO (PATISIRAN) approved by FDA in 2018 for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults}. The research in the field of siRNAs has regianed its enthusiasm, however the siRNAs have certain limitations which are mitigated by chemical modifications thus giving rise to next generation of siRNAs that are chemically modifed. So now chemically modified siRNAs are used and researched upon rather than native ones. There is no pediction system to predict the toxicity of these chemically modified siRNAs therfore we developed the system to answer this question.


Q. What can we do with the webserver?

TOXsiRNA can design the normal siRNAs, generate the single position modifications at each position giving rise to more than 850 chemically modified siRNAs form a single siRNA along with the efficacy of these siRNAs. Furthermore, the user can design any number permutations and combintions of chemical modifications. Besides, the predictor can also predict the efficacy of chemiclaly modified siRNAs as well as their off-targets. the workflow goes like below:


Q. What is the off-target and its importance ?

Off-targets refers to the other unwanted target sites in the nucleotide sequences in the RNA (coding or non-coding) in the cell where the siRNA can bind. A siRNA can have multiple targets like that of microRNA.
It is important to predict the off-target of the siRNA and to choose that one which has no or least off-targets, to eliminate any unwanted effect in the cell.


(II) How To Use Section

Familiarizing with the web server and methodology of chemically modified siRNA toxicity prediction system

We have develop the TOXsiRNA web server in easy and user friendly way as seen from the index or home page below with differnet options shown by red arrows. We have tried to develop the PEPsiRNA webserver in easy and user friendly way as seen from the index or home page.



To srart predicting the siRNAs (normal-non chemicallly modified) start with the TOXsiRNA option as shown in below figure. Paste your query nucleotide sequence and it will predict the normal siRANs with efficacy scores as wll as off-target option.



After submission of the query the results page will be displayed as shown below. Further we can go for two option (A) for generating different chemical modifications of htis sequence automatically and (B) looking for the off-targets of the siRNA sequence.



(A) On clicking one of the siRNA from the list, its variants in terms of the single position (and single chemical modification) based siRNA sequences will be generated automatically (which are more than 800). These chemically modified siRNAs sequences will be displayed in the form of a table with sequence (with modification highlighted in Red color) its modification name and the respective score of toxicity and knockdown efficacy-see below image.




(B) Second option shows the off targets of the seleted siRNA sequence.






GENMod is the next web-page with the option of generating the user defined chemically modified siRNAs with desired permutations and combinations as shown below. the lsit of cheical modifications along with the one letter codes is provided as dropdown option in the web-page.




After submission of the various inputs as shown above and submitting the query, the page will be re-directed to new web-page with the results options as shown below. Futhermore, to predict the toxicity of the siRNA, click on the siRNA (modiifed sequence) and you will land on new web-page with the three toxicity scores and percentage efficacy value.




TOXsi-MODELS web-page takes the input of chemically modified siRNa sequences and genertes the toxicity scores as well as efficacy percentage score as shown in figure below.




siOff-Tar web-page generates the off targets of the given nucleotide sequence based on sequence. We have provided option of the model organism selection as hown in the figure.