Controlling uncertainty in aptamer selection
The search for high-affinity aptamers for targets such as proteins, small molecules, or cancer cells remains a formidable endeavor. Systematic Evolution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these aptamers through evolutionary selection of high-affinity...
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2017
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| Online Access: | http://hdl.handle.net/1721.1/108794 https://orcid.org/0000-0001-8462-5080 |
| _version_ | 1826205012018069504 |
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| author | Spill, Fabian Weinstein, Zohar B. Irani Shemirani, Atena Ho, Nga Desai, Darash Zaman, Muhammad H. |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Spill, Fabian Weinstein, Zohar B. Irani Shemirani, Atena Ho, Nga Desai, Darash Zaman, Muhammad H. |
| author_sort | Spill, Fabian |
| collection | MIT |
| description | The search for high-affinity aptamers for targets such as proteins, small molecules, or cancer cells remains a formidable endeavor. Systematic Evolution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these aptamers through evolutionary selection of high-affinity candidates from a highly diverse random pool. This randomness dictates an unknown population distribution of fitness parameters, encoded by the binding affinities, toward SELEX targets. Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable outcomes. These uncertainties pose a challenge when tuning selection pressures to isolate high-affinity ligands. Here, we present a stochastic hybrid model that describes the evolutionary selection of aptamers to explore the impact of these unknowns. To our surprise, we find that even single copies of high-affinity ligands in a pool of billions can strongly influence population dynamics, yet their survival is highly dependent on chance. We perform Monte Carlo simulations to explore the impact of environmental parameters, such as the target concentration, on selection efficiency in SELEX and identify strategies to control these uncertainties to ultimately improve the outcome and speed of this time- and resource-intensive process. |
| first_indexed | 2024-09-23T13:05:40Z |
| format | Article |
| id | mit-1721.1/108794 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:05:40Z |
| publishDate | 2017 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1087942022-10-01T12:59:17Z Controlling uncertainty in aptamer selection Spill, Fabian Weinstein, Zohar B. Irani Shemirani, Atena Ho, Nga Desai, Darash Zaman, Muhammad H. Massachusetts Institute of Technology. Department of Mechanical Engineering Spill, Fabian The search for high-affinity aptamers for targets such as proteins, small molecules, or cancer cells remains a formidable endeavor. Systematic Evolution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these aptamers through evolutionary selection of high-affinity candidates from a highly diverse random pool. This randomness dictates an unknown population distribution of fitness parameters, encoded by the binding affinities, toward SELEX targets. Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable outcomes. These uncertainties pose a challenge when tuning selection pressures to isolate high-affinity ligands. Here, we present a stochastic hybrid model that describes the evolutionary selection of aptamers to explore the impact of these unknowns. To our surprise, we find that even single copies of high-affinity ligands in a pool of billions can strongly influence population dynamics, yet their survival is highly dependent on chance. We perform Monte Carlo simulations to explore the impact of environmental parameters, such as the target concentration, on selection efficiency in SELEX and identify strategies to control these uncertainties to ultimately improve the outcome and speed of this time- and resource-intensive process. National Cancer Institute (U.S.) (5U01CA177799) 2017-05-10T19:15:00Z 2017-05-10T19:15:00Z 2016-10 2016-03 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/108794 Spill, Fabian; Weinstein, Zohar B.; Irani Shemirani, Atena; Ho, Nga; Desai, Darash and Zaman, Muhammad H. “Controlling Uncertainty in Aptamer Selection.” Proceedings of the National Academy of Sciences 113, no. 43 (October 2016): 12076–12081. © National Academy of Sciences https://orcid.org/0000-0001-8462-5080 en_US http://dx.doi.org/10.1073/pnas.1605086113 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Spill, Fabian Weinstein, Zohar B. Irani Shemirani, Atena Ho, Nga Desai, Darash Zaman, Muhammad H. Controlling uncertainty in aptamer selection |
| title | Controlling uncertainty in aptamer selection |
| title_full | Controlling uncertainty in aptamer selection |
| title_fullStr | Controlling uncertainty in aptamer selection |
| title_full_unstemmed | Controlling uncertainty in aptamer selection |
| title_short | Controlling uncertainty in aptamer selection |
| title_sort | controlling uncertainty in aptamer selection |
| url | http://hdl.handle.net/1721.1/108794 https://orcid.org/0000-0001-8462-5080 |
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