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Detection and Analysis of Amino Acid Insertions and Deletions

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Algorithms and Methods in Structural Bioinformatics

Part of the book series: Computational Biology ((COBO))

Abstract

Despite being a recurring type of sequence variation, amino acid insertions and deletions InDels), their source and resulting functional significance from them, remain rather unexplored areas of structural biology. Recent research endeavors have made it apparent that these kinds of structural variations have a stronger correlation with functional changes in the respective proteins compared to the other kinds of mutations. In this review article, we overview various aspects of InDels, including their origin, their detection among protein sequences, and various methods of analyzing their effects.

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References

  1. Stefano Pascarella and Patrick Argos. Analysis of insertions/deletions in protein structures. Journal of molecular biology, 224(2):461–471, 1992.

    Article  CAS  Google Scholar 

  2. Fereydoun Hormozdiari, Raheleh Salari, Michael Hsing, Alexander Schönhuth, Simon K Chan, S Cenk Sahinalp, and Artem Cherkasov. The effect of insertions and deletions on wirings in protein-protein interaction networks: a large-scale study. Journal of Computational Biology, 16(2):159–167, 2009.

    Google Scholar 

  3. Pravech Ajawatanawong and Sandra L Baldauf. Evolution of protein indels in plants, animals and fungi. BMC evolutionary biology, 13(1):1–15, 2013.

    Google Scholar 

  4. RyangGuk Kim and Jun-tao Guo. Systematic analysis of short internal indels and their impact on protein folding. BMC structural biology, 10(1):1–11, 2010.

    Article  Google Scholar 

  5. Romain A Studer, Benoit H Dessailly, and Christine A Orengo. Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes. Biochemical journal, 449(3):581–594, 2013.

    Google Scholar 

  6. Courtney E Gonzalez, Paul Roberts, and Marc Ostermeier. Fitness effects of single amino acid insertions and deletions in tem-1 β-lactamase. Journal of molecular biology, 431(12):2320–2330, 2019.

    Google Scholar 

  7. Monica Berrondo and Jeffrey J Gray. Computed structures of point deletion mutants and their enzymatic activities. Proteins: Structure, Function, and Bioinformatics, 79(10):2844–2860, 2011.

    Google Scholar 

  8. **g Hu and Pauline C Ng. Sift indel: predictions for the functional effects of amino acid insertions/deletions in proteins. PloS one, 8(10):e77940, 2013.

    Google Scholar 

  9. Maoxuan Lin, Sarah Whitmire, **g Chen, Alvin Farrel, **nghua Shi, and Jun-tao Guo. Effects of short indels on protein structure and function in human genomes. Scientific reports, 7(1):1–9, 2017.

    Article  Google Scholar 

  10. Stefanie Barbirz, Jürgen J Müller, Charlotte Uetrecht, Alvin J Clark, Udo Heinemann, and Robert Seckler. Crystal structure of Escherichia coli phage hk620 tailspike: podoviral tailspike endoglycosidase modules are evolutionarily related. Molecular microbiology, 69(2):303–316, 2008.

    Google Scholar 

  11. Agnes Tóth-Petróczy and Dan S Tawfik. Protein insertions and deletions enabled by neutral roaming in sequence space. Molecular biology and evolution, 30(4):761–771, 2013.

    Google Scholar 

  12. Liat Rockah-Shmuel, Ágnes Tóth-Petróczy, Asaf Sela, Omri Wurtzel, Rotem Sorek, and Dan S Tawfik. Correlated occurrence and bypass of frame-shifting insertion-deletions (indels) to give functional proteins. PLoS genetics, 9(10):e1003882, 2013.

    Google Scholar 

  13. Bijendra Khadka, Mobolaji Adeolu, Robert E Blankenship, and Radhey S Gupta. Novel insights into the origin and diversification of photosynthesis based on analyses of conserved indels in the core reaction center proteins. Photosynthesis research, 131(2):159–171, 2017.

    Google Scholar 

  14. Yuri Wolf, Thomas Madej, Vladimir Babenko, Benjamin Shoemaker, and Anna R Panchenko. Long-term trends in evolution of indels in protein sequences. BMC evolutionary biology, 7(1):1–10, 2007.

    Google Scholar 

  15. Zheng Zhang, **lan Wang, Ya Gong, and Yuezhong Li. Contributions of substitutions and indels to the structural variations in ancient protein superfamilies. BMC genomics, 19(1):1–9, 2018.

    Article  Google Scholar 

  16. Zhe Liu, Huanying Zheng, Huifang Lin, Mingyue Li, Runyu Yuan, **ju Peng, Qianling **ong, Jiufeng Sun, Baisheng Li, Jie Wu, et al. Identification of common deletions in the spike protein of severe acute respiratory syndrome coronavirus 2. Journal of virology, 94(17):e00790–20, 2020.

    Google Scholar 

  17. Yunkai Zhu, Fei Feng, Gaowei Hu, Yuyan Wang, Yin Yu, Yuanfei Zhu, Wei Xu, ** Sun, Wendong Han, Rong Ye, Hongjun Chen, Qiang Ding, Qiliang Cai, Di Qu, Youhua **%20Sun%2C%20Wendong%20Han%2C%20Rong%20Ye%2C%20Hongjun%20Chen%2C%20Qiang%20Ding%2C%20Qiliang%20Cai%2C%20Di%20Qu%2C%20Youhua%20**e%2C%20Zhenghong%20Yuan%2C%20and%20Rong%20Zhang.%20The%20s1%2Fs2%20boundary%20of%20sars-cov-2%20spike%20protein%20modulates%20cell%20entry%20pathways%20and%20transmission.%20bioRxiv%2C%202020."> Google Scholar 

  18. HA Lewis, C Wang, X Zhao, Y Hamuro, K Conners, MC Kearins, F Lu, JM Sauder, KS Molnar, SJ Coales, et al. Structure and dynamics of nbd1 from cftr characterized using crystallography and hydrogen/deuterium exchange mass spectrometry. Journal of molecular biology, 396(2):406–430, 2010.

    Article  CAS  Google Scholar 

  19. Elisa Donnard, Paula F Asprino, Bruna R Correa, Fabiana Bettoni, Fernanda C Koyama, Fabio CP Navarro, Rodrigo O Perez, John Mariadason, Oliver M Sieber, Robert L Strausberg, et al. Mutational analysis of genes coding for cell surface proteins in colorectal cancer cell lines reveal novel altered pathways, druggable mutations and mutated epitopes for targeted therapy. Oncotarget, 5(19):9199, 2014.

    Google Scholar 

  20. Prathima Iengar. An analysis of substitution, deletion and insertion mutations in cancer genes. Nucleic acids research, 40(14):6401–6413, 2012.

    Article  CAS  Google Scholar 

  21. Michael Hsing and Artem Cherkasov. Indel pdb: a database of structural insertions and deletions derived from sequence alignments of closely related proteins. BMC bioinformatics, 9(1):1–12, 2008.

    Article  Google Scholar 

  22. Pravech Ajawatanawong, Gemma C Atkinson, Nathan S Watson-Haigh, Bryony MacKenzie, and Sandra L Baldauf. Seqfire: a web application for automated extraction of indel regions and conserved blocks from protein multiple sequence alignments. Nucleic acids research, 40(W1):W340–W347, 2012.

    Google Scholar 

  23. Zheng Zhang, Cheng **ng, Lushan Wang, Bin Gong, and Hui Liu. Indelfr: a database of indels in protein structures and their flanking regions. Nucleic acids research, 40(D1):D512–D518, 2012.

    Article  Google Scholar 

  24. Mufleh Al-Shatnawi, M Omair Ahmad, and MNS Swamy. Msaindelfr: a scheme for multiple protein sequence alignment using information on indel flanking regions. BMC bioinformatics, 16(1):1–11, 2015.

    Google Scholar 

  25. Stephane Emond, Maya Petek, Emily J Kay, Brennen Heames, Sean RA Devenish, Nobuhiko Tokuriki, and Florian Hollfelder. Accessing unexplored regions of sequence space in directed enzyme evolution via insertion/deletion mutagenesis. Nature communications, 11(1):1–14, 2020.

    Google Scholar 

  26. Shu-su Liu, Xuan Wei, Qun Ji, **u **n, Biao Jiang, and Jia Liu. A facile and efficient transposon mutagenesis method for generation of multi-codon deletions in protein sequences. Journal of biotechnology, 227:27–34, 2016.

    Article  CAS  Google Scholar 

  27. Carlos Bermejo-Das-Neves, Hoan-Ngoc Nguyen, Olivier Poch, and Julie D Thompson. A comprehensive study of small non-frameshift insertions/deletions in proteins and prediction of their phenotypic effects by a machine learning method (kd4i). BMC bioinformatics, 15(1):1–20, 2014.

    Google Scholar 

  28. Anupam Banerjee, Yaakov Levy, and Pralay Mitra. Analyzing change in protein stability associated with single point deletions in a newly defined protein structure database. Journal of proteome research, 18(3):1402–1410, 2019.

    Article  CAS  Google Scholar 

  29. Anupam Banerjee, Amit Kumar, Kushal Kanti Ghosh, and Pralay Mitra. Estimating change in foldability due to multipoint deletions in protein structures. Journal of Chemical Information and Modeling, 60(12):6679–6690, 2020.

    Google Scholar 

  30. Gil Loewenthal, Dana Rapoport, Oren Avram, Asher Moshe, Alon Itzkovitch, Omer Israeli, Dana Azouri, Reed Austin Cartwright, Itay Mayrose, and Tal Pupko. A probabilistic model for indel evolution: differentiating insertions from deletions. bioRxiv, 2020.

    Google Scholar 

  31. Mufleh Al-Shatnawi, M Omair Ahmad, and MN Shanmukha Swamy. Prediction of indel flanking regions in protein sequences using a variable-order Markov model. Bioinformatics, 31(1):40–47, 2015.

    Google Scholar 

  32. Yongwook Choi and Agnes P Chan. Provean web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics, 31(16):2745–2747, 2015.

    Google Scholar 

  33. Maya Petek. Characterising fitness landscapes of protein evolution by next-generation sequencing. PhD thesis, University of Cambridge, 2020.

    Google Scholar 

  34. Zheng Zhang, Yuxiao Wang, Lushan Wang, and Peiji Gao. The combined effects of amino acid substitutions and indels on the evolution of structure within protein families. PloS one, 5(12):e14316, 2010.

    Google Scholar 

  35. Ágnes Tóth-Petróczy and Dan S Tawfik. Hopeful (protein indel) monsters? Structure, 22(6):803–804, 2014.

    Google Scholar 

  36. Raheleh Salari, Alexander Schönhuth, Fereydoun Hormozdiari, Artem Cherkasov, and S Cenk Sahinalp. The relation between indel length and functional divergence: a formal study. In International Workshop on Algorithms in Bioinformatics, pages 330–341. Springer, 2008.

    Google Scholar 

  37. Muneeba Jilani, Alistair Turcan, Nurit Haspel, and Filip Jagodzinski. Assessing the effects of amino acid insertion and deletion mutations. In 2021 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), pages 2511–2518. IEEE, 2021.

    Google Scholar 

  38. Fanny S Krebs, Vincent Zoete, Maxence Trottet, Timothée Pouchon, Christophe Bovigny, and Olivier Michielin. Swiss-po: a new tool to analyze the impact of mutations on protein three-dimensional structures for precision oncology. NPJ precision oncology, 5(1):1–9, 2021.

    Google Scholar 

  39. James AJ Arpino, Samuel C Reddington, Lisa M Halliwell, Pierre J Rizkallah, and D Dafydd Jones. Random single amino acid deletion sampling unveils structural tolerance and the benefits of helical registry shift on gfp folding and structure. Structure, 22(6):889–898, 2014.

    Google Scholar 

  40. Shu-su Liu, Xuan Wei, Xue Dong, Liang Xu, Jia Liu, and Biao Jiang. Structural plasticity of green fluorescent protein to amino acid deletions and fluorescence rescue by folding-enhancing mutations. BMC biochemistry, 16(1):1–11, 2015.

    Article  Google Scholar 

  41. James AJ Arpino, Pierre J Rizkallah, and D Dafydd Jones. Structural and dynamic changes associated with beneficial engineered single-amino-acid deletion mutations in enhanced green fluorescent protein. Acta Crystallographica Section D: Biological Crystallography, 70(8):2152–2162, 2014.

    Google Scholar 

  42. Kazufumi Takano, Yuriko Yamagata, and Katsuhide Yutani. Role of amino acid residues at turns in the conformational stability and folding of human lysozyme. Biochemistry, 39(29):8655–8665, 2000.

    Article  CAS  Google Scholar 

  43. Yulian Gavrilov, Shlomi Dagan, and Yaakov Levy. Shortening a loop can increase protein native state entropy. Proteins: Structure, Function, and Bioinformatics, 83(12):2137–2146, 2015.

    Article  CAS  Google Scholar 

  44. Yulian Gavrilov, Shlomi Dagan, Ziv Reich, Tali Scherf, and Yaakov Levy. An nmr confirmation for increased folded state entropy following loop truncation. The Journal of Physical Chemistry B, 122(48):10855–10860, 2018.

    Article  CAS  Google Scholar 

  45. Eleisha L Jackson, Stephanie J Spielman, and Claus O Wilke. Computational prediction of the tolerance to amino-acid deletion in green-fluorescent protein. PloS one, 12(4):e0164905, 2017.

    Google Scholar 

  46. Sara Light, Rauan Sagit, Diana Ekman, and Arne Elofsson. Long indels are disordered: a study of disorder and indels in homologous eukaryotic proteins. Biochimica Et Biophysica Acta (BBA)-Proteins and Proteomics, 1834(5):890–897, 2013.

    Article  CAS  Google Scholar 

  47. Qi Wang, Esley Heizer, Bruce A Rosa, Scott A Wildman, James W Janetka, and Makedonka Mitreva. Characterization of parasite-specific indels and their proposed relevance for selective anthelminthic drug targeting. Infection, Genetics and Evolution, 39:201–211, 2016.

    Google Scholar 

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Authors and Affiliations

  1. University of Massachusetts Boston, Boston, MA, USA

    Muneeba Jilani & Nurit Haspel

  2. Western Washington University, Bellingham, WA, USA

    Filip Jagodzinski

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  1. Muneeba Jilani
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  2. Nurit Haspel
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  3. Filip Jagodzinski
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Correspondence to Nurit Haspel .

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Editors and Affiliations

  1. Department of Computer Science, University of Massachusetts Boston, Boston, MA, USA

    Nurit Haspel

  2. Computer Science, Western Washington University, Bellingham, WA, USA

    Filip Jagodzinski

  3. ISAT/CS Building Room 216, James Madison University, Harrisonburg, VA, USA

    Kevin Molloy

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Jilani, M., Haspel, N., Jagodzinski, F. (2022). Detection and Analysis of Amino Acid Insertions and Deletions. In: Haspel, N., Jagodzinski, F., Molloy, K. (eds) Algorithms and Methods in Structural Bioinformatics. Computational Biology. Springer, Cham. https://doi.org/10.1007/978-3-031-05914-8_5

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  • DOI: https://doi.org/10.1007/978-3-031-05914-8_5

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  • Online ISBN: 978-3-031-05914-8

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