Large-scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discovery
The naïve human antibody repertoire has theoretical access to an estimated > 1015 antibodies. Identifying subsets of this prohibitively large space where therapeutically relevant antibodies may be found is useful for development of these agents. It was previously demonstrated that, despite the im...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | mAbs |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2024.2361928 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832576627456868352 |
|---|---|
| author | Pawel Dudzic Dawid Chomicz Jarosław Kończak Tadeusz Satława Bartosz Janusz Sonia Wrobel Tomasz Gawłowski Igor Jaszczyszyn Weronika Bielska Samuel Demharter Roberto Spreafico Lukas Schulte Kyle Martin Stephen R. Comeau Konrad Krawczyk |
| author_facet | Pawel Dudzic Dawid Chomicz Jarosław Kończak Tadeusz Satława Bartosz Janusz Sonia Wrobel Tomasz Gawłowski Igor Jaszczyszyn Weronika Bielska Samuel Demharter Roberto Spreafico Lukas Schulte Kyle Martin Stephen R. Comeau Konrad Krawczyk |
| author_sort | Pawel Dudzic |
| collection | DOAJ |
| description | The naïve human antibody repertoire has theoretical access to an estimated > 1015 antibodies. Identifying subsets of this prohibitively large space where therapeutically relevant antibodies may be found is useful for development of these agents. It was previously demonstrated that, despite the immense sequence space, different individuals can produce the same antibodies. It was also shown that therapeutic antibodies, which typically follow seemingly unnatural development processes, can arise independently naturally. To check for biases in how the sequence space is explored, we data mined public repositories to identify 220 bioprojects with a combined seven billion reads. Of these, we created a subset of human bioprojects that we make available as the AbNGS database (https://naturalantibody.com/ngs/). AbNGS contains 135 bioprojects with four billion productive human heavy variable region sequences and 385 million unique complementarity-determining region (CDR)-H3s. We find that 270,000 (0.07% of 385 million) unique CDR-H3s are highly public in that they occur in at least five of 135 bioprojects. Of 700 unique therapeutic CDR-H3, a total of 6% has direct matches in the small set of 270,000. This observation extends to a match between CDR-H3 and V-gene call as well. Thus, the subspace of shared (‘public’) CDR-H3s shows utility for serving as a starting point for therapeutic antibody design. |
| format | Article |
| id | doaj-art-7c74ae2f3b3c4564ab5b22c1be596002 |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-7c74ae2f3b3c4564ab5b22c1be5960022025-01-31T04:19:37ZengTaylor & Francis GroupmAbs1942-08621942-08702024-12-0116110.1080/19420862.2024.2361928Large-scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discoveryPawel Dudzic0Dawid Chomicz1Jarosław Kończak2Tadeusz Satława3Bartosz Janusz4Sonia Wrobel5Tomasz Gawłowski6Igor Jaszczyszyn7Weronika Bielska8Samuel Demharter9Roberto Spreafico10Lukas Schulte11Kyle Martin12Stephen R. Comeau13Konrad Krawczyk14NaturalAntibody, Szczecin, PolandNaturalAntibody, Szczecin, PolandNaturalAntibody, Szczecin, PolandNaturalAntibody, Szczecin, PolandNaturalAntibody, Szczecin, PolandNaturalAntibody, Szczecin, PolandNaturalAntibody, Szczecin, PolandNaturalAntibody, Szczecin, PolandNaturalAntibody, Szczecin, PolandDiscovery Data Science, Genmab, Copenhagen, DenmarkDiscovery Data Science, Genmab, Utrecht, The NetherlandsGlobal Computational Biology & Digital Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, GermanyBiotherapeutics Discovery, Boehringer Ingelheim, Ridgefield, CT, USABiotherapeutics Discovery, Boehringer Ingelheim, Ridgefield, CT, USANaturalAntibody, Szczecin, PolandThe naïve human antibody repertoire has theoretical access to an estimated > 1015 antibodies. Identifying subsets of this prohibitively large space where therapeutically relevant antibodies may be found is useful for development of these agents. It was previously demonstrated that, despite the immense sequence space, different individuals can produce the same antibodies. It was also shown that therapeutic antibodies, which typically follow seemingly unnatural development processes, can arise independently naturally. To check for biases in how the sequence space is explored, we data mined public repositories to identify 220 bioprojects with a combined seven billion reads. Of these, we created a subset of human bioprojects that we make available as the AbNGS database (https://naturalantibody.com/ngs/). AbNGS contains 135 bioprojects with four billion productive human heavy variable region sequences and 385 million unique complementarity-determining region (CDR)-H3s. We find that 270,000 (0.07% of 385 million) unique CDR-H3s are highly public in that they occur in at least five of 135 bioprojects. Of 700 unique therapeutic CDR-H3, a total of 6% has direct matches in the small set of 270,000. This observation extends to a match between CDR-H3 and V-gene call as well. Thus, the subspace of shared (‘public’) CDR-H3s shows utility for serving as a starting point for therapeutic antibody design.https://www.tandfonline.com/doi/10.1080/19420862.2024.2361928CDR-H3databaserepertoire |
| spellingShingle | Pawel Dudzic Dawid Chomicz Jarosław Kończak Tadeusz Satława Bartosz Janusz Sonia Wrobel Tomasz Gawłowski Igor Jaszczyszyn Weronika Bielska Samuel Demharter Roberto Spreafico Lukas Schulte Kyle Martin Stephen R. Comeau Konrad Krawczyk Large-scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discovery mAbs CDR-H3 database repertoire |
| title | Large-scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discovery |
| title_full | Large-scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discovery |
| title_fullStr | Large-scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discovery |
| title_full_unstemmed | Large-scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discovery |
| title_short | Large-scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discovery |
| title_sort | large scale data mining of four billion human antibody variable regions reveals convergence between therapeutic and natural antibodies that constrains search space for biologics drug discovery |
| topic | CDR-H3 database repertoire |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2024.2361928 |
| work_keys_str_mv | AT paweldudzic largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT dawidchomicz largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT jarosławkonczak largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT tadeuszsatława largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT bartoszjanusz largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT soniawrobel largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT tomaszgawłowski largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT igorjaszczyszyn largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT weronikabielska largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT samueldemharter largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT robertospreafico largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT lukasschulte largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT kylemartin largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT stephenrcomeau largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery AT konradkrawczyk largescaledataminingoffourbillionhumanantibodyvariableregionsrevealsconvergencebetweentherapeuticandnaturalantibodiesthatconstrainssearchspaceforbiologicsdrugdiscovery |