Name the modification list and symbols used?

Following is the list of the chemically modified nucleic acids used in the development of SMEpred webserver. List contains 5 usual (A,T,G,C,U) and 30 modified Nucleic Acids.

S. No One letter Code Chemical Modification name list
1 B 2'-N-Adamant-1-yl-Methylcarbonyl-2'-Amino-Locked Nucleic Acid
2 D 2'-Aminoethoxymethyl Nucleic Acid
3 E 2'-Aminoethyl Nucleic Acid
4 F 2'-Fluoro Nucleic Acid
5 H 4'-C-Hydroxymethyl Deoxyribonucleic acid
6 I Altritol Nucleic Acid
7 J 2'-Aminopropyl Nucleic Acid
8 K 2'-aminopropoxymethyl Nucleic Acid
9 L Locked Nucleic Acid
10 M 2'-Deoxy-2'-N,4'-C-Ethylene-Locked Nucleic Acid
11 N Alfa-L-Locked Nucleic Acid
12 O 2'-Cyanoethyl Nucleic Acid
13 P 2',4'-Carbocyclic-Ethylene-bridged Nucleic Acid-Locked Nucleic Acid
14 Q 2',4'-Carbocyclic-Locked Nucleic Acid-Locked Nucleic Acid
15 R 2'-Guanidinoethyl Nucleic Acid
16 S Hexitol Nucleic Acid
17 V Oxetane-Locked Nucleic Acid
18 W 2'-N-Pyren-1-yl Methyl-2'-Amino-Locked Nucleic Acid
19 X Unlocked Nucleic Acid
20 Y 2'-O-Methyl Nucleic Acid
21 Z 2'-Deoxy Nucleic Acid
22 b 2'-Deoxy-2'-Fluoro Nucleic Acid
23 d 2'-O-Benzyl Nucleic Acid
24 e 2'-O-Guanidinopropyl Nucleic Acid
25 g Boranophosphate Nucleic Acid
26 h Dihydrouridine Nucleic Acid
27 m Hypoxanthine Nucleic Acid
28 n Peptide Nucleic Acids
29 q Phosphorothioate Nucleic Acid
30 r Tricyclodeoxyribo Nucleic Acid
S. No One letter Code Usual Nucleic acids
1 A Adenosine Nucleic Acid
2 C Cytosine Nucleic Acid
3 G Guanosine Nucleic Acid
4 T Thymidine Nucleic Acid
5 U Uridine Nucleic Acid

What is SMEpred?

SMEpred workbench is the first webserver to design and predicts the efficacy of chemically modified siRNAs (cm-siRNAs) on multiple nucleotide locations. siRNAs can be generated from its gene or mRNA sequence using SMEpred-algorithm, which are subsequently modified on single places with different modifiations and their efficacy predicted. Furthermore, Custom chemical modifications in unmodified siRNA sequences can be generated using MultiModGen algorithm.

How to use the SMEpred?

1) Paste the mRNA sequence or gene sequence in fasta format to generate siRNA(s). Choose the siRNA that has the highest inhibition value. click on the siRNa of your choice and 1260 cm-siRNAs will be generated form the single sequencewith 30 different modifications on each position of siRNA.

2) Click on the siRNA of your choice and 1260 cm-siRNAs will be generated form the single sequence with 30 different modifications on each position of siRNA.

3) For multiple modifications on different positions select MultiModGen algorithm to generate the multi-modified cm-siRNA sequence. Submit your siRNA sequence(s), position(s) and one-letter symbols of the modification(s). Click on the sequence of your choice and it will predict its score.

4) Furthermore, siMepred-tool can be utilised to explore the various components of the cm-siRNA. There are three models installed in the background, Model-A, Model-B and Model-C.

After submitting the data, we will get the output in the form of table giving the model score in terms of efficacy of the desired cm-siRNA. Only sequence(s) format with chemical modifications represented by single letter code (list of chemical modifications and one-letter symbols above) will be entertained and predicted correctly.

How should I enter input in SMEpred?

Simply paste gene or mRNA sequence in fasta format in the provided space on the page.

What will be the output from SMEpred?

In the first part of pipeline, the output result displays 3 columns. The 1st column display serial no., 2nd and 3rd column displays sequence and predicted score of the siRNAs generated. In second part, we have to select the siRNA to generate its 1260 cm-siRNAs (these are generated from 30 different modifiations at 21 positions on 2 strands on each siRNA). User can download the output via download option provided on the page.



What is MultiModGen?

MultiModGen is an algorithm that allows user to custom create different chemical modifications (30 most commonly used chemical modifications) on multiple locations in normal input siRNA sequences (position 1 to 21) i.e. it will create user defined nucleotide modification at given positions. In case of two or more modifications are to be done in the same siRNA sequence, user need to input the two symbols for two modifications need to be sepatated by double commas (,,) snd so should be the corresponing positions provided, seperated by the double commas (,,) respectively. For example if user wants to modify sequence by 'M' and 'P' modification input should be as F,,T-T and the positions be as 2,5,7,10,11,12,13,14,15,16,,20,21-20,21. ie 'F,,T' modification be placed on the 2,5,7,10,11,12,13,14,15,16,,20,21 and 'T' on posistions 20 and 21 figure below shows the pictorialy representation of same. After getting custom modifications in siRNA sequences user can submit these multi-modified cm-siRNAs and their predicted efficacy score willl be generated.

The output result displays four columns with siRNA wild sequence, modifications, positions and modified siRNA sequences. User can also download results by clicking download option.


What is siMEpred-tool and what is its significance?

siMEpred-tool is an algorithm that can be used to explore the different fragments of antisense siRNA strand. It has three different models in it. Model-A is the default onebased on mononucleotide composition (MNC) with hisghest PCC value achieved during training/testing. Model-B and Model-C are based MNC and binnary (positional) pattern, with 13-nucleotide pattern for forrmer one and last 8-nucleotide binnary pattern for latter model. This tool can be explored the position of modification in antisense seed region (13-nucleotides from 5'-end--Model-B) and non-seed region (8-nucleotides from 3'-end-- Model-C).