Basic reporting Authors has made excellent efforts in compiling the MS with detailed, clearly, consistently communicated a rational design followed by their outcomes, interpretation and significance of the work.

Experimental design No changes required in the compiled version

Validity of the findings Author has made great effort in contributing the new novelty in the present MS. My detail comments are in the author section.

Additional comments The topic seems excellent addition in the current literature however, before accepting for the publication, it should advisable to refine further by making necessary minor corrections as suggested in the bottom which should provide more clarity to readers.

Comments on Manuscript Couple of Comments/suggestion should be incorporate to improve English, Formatting and Uniformity. 1. Title-Please include the before the Notch family 2. Affiliation 5, cedex should have ‘C’ in capital letter 3. Line 50, abstract, please add ‘s’ after human 4. Line 73, Introduction: replace ‘to’ with ‘in’ 5. Line 76, provide symbol for approximation and replace the word amino acids with ‘aa’ for uniformity 6. Line 97, insert comma after TAD domain 7. Line 97, remove the word in before the length 8. Line 98, remove the before vascular….. 9. Line 101, add ‘the’ after involved in, so sentence looks like The pathway is involved in the…. 10. Line 102, Insert comma, after learning 11. Line 113, insert ‘s’ after score; 114, replace which with that; Line 115, symbol will come before 95% 12. Line 137, insert ‘a’ before threshold 13. Line 158, insert ‘to’ before as noisy…. 14. Line 136, in the Figure 1, author should provide axis information along with as an insert total number of protein 15. Line 166, insert amino acids or aa after 4835 16. Line 185, replace a with the before most conserved site….. 17. Line 193, insert ‘s’ after alignment… 18. Line 196, delete ‘a’ before non-polar 19. Line 198, add they after since….are repeated…. 20. Line 205, insert ‘the’ before evolutionary history…… 21. Line 206, replace the It’s remarkable that with Remarkably,…… 22. Line 207, insert ‘ly’ after significant 23. Line 217, Correct the spelling of Caenorabditis…… 24. Line 221, insert ‘s’ after appear 25. Line 224, delete ‘of’ before containing calcium….. 26. Line 225 and 226, replace ‘s’ with ‘z’ for the word heterodimeri…. 27. Line 237, insert ‘the’ before human notch1 28. Line 243, charge on calcium should be superscript and similar mistakes should be corrected other places 29. Line 275, add with and delete to comes before the possibility,,,,, 30. Line 320, rewrite the sentence like be at the beginning of… 31. Line 343, remove ‘A number of’ and start the statement with Several……., replace has with have 32. Line 347, insert ‘s’ after year… and replace showed with shown…. 33. Line 374, remove ‘the’ before half of our….. 34. Line 375, remove are before the bacteria.. 35. Line 450-452; 472-475; 530-533, remove the additional duplicate reference from the MS.

Basic reporting Authors is advised to proof read again the MS as there are very minor improvement is required in terms of grammar.

Experimental design Authors has made necessary revisions in the revised MS

Validity of the findings No Changes

Additional comments The authors has made suggested changes in the revised MS and I do not have any additional correction in the present form of MS