Assembly of a pan-genome from deep sequencing of 910 humans of African descent

Rachel M. Sherman; Juliet Forman; Valentin Antonescu; Daniela Puiu; Michelle Daya; Nicholas Rafaels; Meher Preethi Boorgula; Sameer Chavan; Candelaria Vergara; Victor E. Ortega; Albert M. Levin; Celeste Eng; Maria Yazdanbakhsh; James G. Wilson; Javier Marrugo; Leslie A. Lange; L. Keoki Williams; Harold Watson; Lorraine B. Ware; Christopher O. Olopade; Olufunmilayo Olopade; Ricardo R. Oliveira; Carole Ober; Dan L. Nicolae; Deborah A. Meyers; Alvaro Mayorga; Jennifer Knight-Madden; Tina Hartert; Nadia N. Hansel; Marilyn G. Foreman; Jean G. Ford; Mezbah U. Faruque; Georgia M. Dunston; Luis Caraballo; Esteban G. Burchard; Eugene R. Bleecker; Maria I. Araujo; Edwin F. Herrera-Paz; Monica Campbell; Cassandra Foster; Margaret A. Taub; Terri H. Beaty; Ingo Ruczinski; Rasika A. Mathias; Kathleen C. Barnes; Steven L. Salzberg

doi:10.1038/s41588-018-0273-y

Assembly of a pan-genome from deep sequencing of 910 humans of African descent

Rachel M. Sherman, Juliet Forman, Valentin Antonescu, Daniela Puiu, Michelle Daya, Nicholas Rafaels, Meher Preethi Boorgula, Sameer Chavan, Candelaria Vergara, Victor E. Ortega, Albert M. Levin, Celeste Eng, Maria Yazdanbakhsh, James G. Wilson, Javier Marrugo, Leslie A. Lange, L. Keoki Williams, Harold Watson, Lorraine B. Ware, Christopher O. OlopadeOlufunmilayo Olopade, Ricardo R. Oliveira, Carole Ober, Dan L. Nicolae, Deborah A. Meyers, Alvaro Mayorga, Jennifer Knight-Madden, Tina Hartert, Nadia N. Hansel, Marilyn G. Foreman, Jean G. Ford, Mezbah U. Faruque, Georgia M. Dunston, Luis Caraballo, Esteban G. Burchard, Eugene R. Bleecker, Maria I. Araujo, Edwin F. Herrera-Paz, Monica Campbell, Cassandra Foster, Margaret A. Taub, Terri H. Beaty, Ingo Ruczinski, Rasika A. Mathias, Kathleen C. Barnes, Steven L. Salzberg

Medicine

Research output: Contribution to journal › Letter › peer-review

241 Scopus citations

Abstract

We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.

Original language	English (US)
Pages (from-to)	30-35
Number of pages	6
Journal	Nature Genetics
Volume	51
Issue number	1
DOIs	https://doi.org/10.1038/s41588-018-0273-y
State	Published - Jan 1 2019

ASJC Scopus subject areas

Genetics

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Sherman, R. M., Forman, J., Antonescu, V., Puiu, D., Daya, M., Rafaels, N., Boorgula, M. P., Chavan, S., Vergara, C., Ortega, V. E., Levin, A. M., Eng, C., Yazdanbakhsh, M., Wilson, J. G., Marrugo, J., Lange, L. A., Williams, L. K., Watson, H., Ware, L. B., ... Salzberg, S. L. (2019). Assembly of a pan-genome from deep sequencing of 910 humans of African descent. Nature Genetics, 51(1), 30-35. https://doi.org/10.1038/s41588-018-0273-y

Sherman, RM, Forman, J, Antonescu, V, Puiu, D, Daya, M, Rafaels, N, Boorgula, MP, Chavan, S, Vergara, C, Ortega, VE, Levin, AM, Eng, C, Yazdanbakhsh, M, Wilson, JG, Marrugo, J, Lange, LA, Williams, LK, Watson, H, Ware, LB, Olopade, CO, Olopade, O, Oliveira, RR, Ober, C, Nicolae, DL, Meyers, DA, Mayorga, A, Knight-Madden, J, Hartert, T, Hansel, NN, Foreman, MG, Ford, JG, Faruque, MU, Dunston, GM, Caraballo, L, Burchard, EG, Bleecker, ER, Araujo, MI, Herrera-Paz, EF, Campbell, M, Foster, C, Taub, MA, Beaty, TH, Ruczinski, I, Mathias, RA, Barnes, KC & Salzberg, SL 2019, 'Assembly of a pan-genome from deep sequencing of 910 humans of African descent', Nature Genetics, vol. 51, no. 1, pp. 30-35. https://doi.org/10.1038/s41588-018-0273-y

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title = "Assembly of a pan-genome from deep sequencing of 910 humans of African descent",

abstract = "We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.",

author = "Sherman, {Rachel M.} and Juliet Forman and Valentin Antonescu and Daniela Puiu and Michelle Daya and Nicholas Rafaels and Boorgula, {Meher Preethi} and Sameer Chavan and Candelaria Vergara and Ortega, {Victor E.} and Levin, {Albert M.} and Celeste Eng and Maria Yazdanbakhsh and Wilson, {James G.} and Javier Marrugo and Lange, {Leslie A.} and Williams, {L. Keoki} and Harold Watson and Ware, {Lorraine B.} and Olopade, {Christopher O.} and Olufunmilayo Olopade and Oliveira, {Ricardo R.} and Carole Ober and Nicolae, {Dan L.} and Meyers, {Deborah A.} and Alvaro Mayorga and Jennifer Knight-Madden and Tina Hartert and Hansel, {Nadia N.} and Foreman, {Marilyn G.} and Ford, {Jean G.} and Faruque, {Mezbah U.} and Dunston, {Georgia M.} and Luis Caraballo and Burchard, {Esteban G.} and Bleecker, {Eugene R.} and Araujo, {Maria I.} and Herrera-Paz, {Edwin F.} and Monica Campbell and Cassandra Foster and Taub, {Margaret A.} and Beaty, {Terri H.} and Ingo Ruczinski and Mathias, {Rasika A.} and Barnes, {Kathleen C.} and Salzberg, {Steven L.}",

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AU - Sherman, Rachel M.

AU - Forman, Juliet

AU - Antonescu, Valentin

AU - Puiu, Daniela

AU - Daya, Michelle

AU - Rafaels, Nicholas

AU - Boorgula, Meher Preethi

AU - Chavan, Sameer

AU - Vergara, Candelaria

AU - Ortega, Victor E.

AU - Levin, Albert M.

AU - Eng, Celeste

AU - Yazdanbakhsh, Maria

AU - Wilson, James G.

AU - Marrugo, Javier

AU - Lange, Leslie A.

AU - Williams, L. Keoki

AU - Watson, Harold

AU - Ware, Lorraine B.

AU - Olopade, Christopher O.

AU - Olopade, Olufunmilayo

AU - Oliveira, Ricardo R.

AU - Ober, Carole

AU - Nicolae, Dan L.

AU - Meyers, Deborah A.

AU - Mayorga, Alvaro

AU - Knight-Madden, Jennifer

AU - Hartert, Tina

AU - Hansel, Nadia N.

AU - Foreman, Marilyn G.

AU - Ford, Jean G.

AU - Faruque, Mezbah U.

AU - Dunston, Georgia M.

AU - Caraballo, Luis

AU - Burchard, Esteban G.

AU - Bleecker, Eugene R.

AU - Araujo, Maria I.

AU - Herrera-Paz, Edwin F.

AU - Campbell, Monica

AU - Foster, Cassandra

AU - Taub, Margaret A.

AU - Beaty, Terri H.

AU - Ruczinski, Ingo

AU - Mathias, Rasika A.

AU - Barnes, Kathleen C.

AU - Salzberg, Steven L.

PY - 2019/1/1

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N2 - We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.

AB - We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.

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SP - 30

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JO - Nature Genetics

JF - Nature Genetics

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Assembly of a pan-genome from deep sequencing of 910 humans of African descent

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