Publications

‡ Indicates co-first authorship

Annotations are in the spirit of the San Francisco Declaration On Research Assessment (SF DORA)

See also: Google Scholar Profile

SELECTED PEER-REVIEWED PUBLICATIONS, ANNOTATED

Altemose N (2022). [Review]

A classical revival: Human satellite DNAs enter the genomics era. Seminars in Cell and Developmental Biology, 128, 2-14. 

https://doi.org/10.1016/j.semcdb.2022.04.012 [open-access preprint available]

Li R‡, Bitoun E‡, Altemose N‡, Davies RW, Davies B, Myers SR (2019).

A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination. Nature Communications, 10, 1-15. 

https://doi.org/10.1038/s41467-019-11675-y [open access, transparent review]

• In this article, we present the highest-resolution map ever of mammalian non-crossover gene conversion events, which are difficult to detect and study despite their high frequency in each meiosis. To accomplish this, we bred hybrid transgenic mice over 5 generations and deeply sequenced genomic DNA from over 100 offspring. Because these mice have high sequence diversity, we were able to detect short non-crossover gene conversions with unprecedented sensitivity and spatial resolution and discovered several new, fundamental properties of mammalian meiotic recombination. Most importantly, we found strong evidence that the protein PRDM9 not only positions DNA double-strand breaks across the genome, but also guides their repair by binding to both homologous chromosomes. This study represents one of my major research projects from Oxford, which I started in my final years. Reviewers called this work a “tour de force” and a “valuable resource for the community.”

Altemose N, Noor N, Bitoun E, Tumian A, Imbeault M, Chapman R, Aricescu AR, Myers SR (2017).

A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis. eLife, 6, e28383. 

https://doi.org/10.7554/eLife.28383 [open access, transparent review]

• This paper encompasses several additional branches of my thesis work from Oxford. By building a high-resolution binding map of the meiotic recombination protein PRDM9 in a human cell line and comparing it to measurements of histone modifications, gene expression, and meiotic recombination rates, we discovered several novel properties of PRDM9 with consequences for fertility, genome evolution, and speciation. We made the surprising discovery that PRDM9 frequently binds gene promoters and can even activate the expression of a small number of genes, expanding its known functions and evolutionary constraints. We also found that PRDM9 can bind different DNA motifs with different subsets and arrangements of its zinc fingers, and we showed that its zinc fingers are responsible for forming PRDM9 multimers. To perform these analyses, we developed a new ChIP-seq peak-calling algorithm as well as a new ab initio motif-finding algorithm that allows for joint discovery of multiple binding motifs with variable internal spacing. Our binding map, biological insights, and methods have proven useful for other groups.

Davies B‡, Hatton E‡, Altemose N, Hussin JG, Pratto F, Zhang G, Hinch AG, Moralli D, Biggs D, Diaz R, Preece C, Li R, Brick K, Green CM, Camerini-Otero RD, Myers SR, and Donnelly P (2016).

Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice. Nature, 530(7589), 171–176. 

https://doi.org/10.1038/nature16931 [free to read on PubMed Central]

• This study proposes the first molecular mechanism of speciation in any mammal, resulting from a collaboration between four research groups (Ben Davies, R. Dan Camerini-Otero, Simon Myers, Peter Donnelly). Using maps of PRDM9 binding and double-strand break formation, we discovered that PRDM9-related hybrid infertility can be explained by PRDM9 binding unequally to each homologous chromosome at each binding site. My contribution stems from a chapter of my thesis work. I helped design all experiments, led the breeding of hybrid mice, performed and analyzed the PRDM9 binding experiments, and generated the fourth and final main text figure. My data and analyses proved essential for illuminating the proposed mechanism and reaching the main conclusion of the paper. Our results have inspired further investigations into this speciation mechanism by others. 
• A news & views summary of the article is available at: https://www.nature.com/articles/nature16870 

Altemose N, Hayden KE, Maggioni M, Willard HF (2014).

Genomic characterization of large heterochromatic gaps in the human genome assembly. PLoS Computational Biology, 10(5), e1003628. 

https://doi.org/10.1371/journal.pcbi.1003628 [open access]

• This study represents the first comprehensive genome-wide study of Human Satellites 2 and 3, which are poorly understood repetitive sequences that comprise 1-3% of the human genome and correspond to the largest gaps in the hg38 reference sequence. As an undergraduate, I developed new computational methods to cluster and map these missing sequences genome-wide for the first time, and I provided resources, including a pseudo-reference, for their further study. By applying these resources, I discovered that a repetitive region of the Y chromosome can vary from 7 to 98 million base pairs among XY individuals, demonstrating that a large share of human genetic variation is still missing from the human reference assembly. The pseudo-reference that I published alongside this paper has been used by other groups to image and measure expression from these regions of the genome. Its conclusions and predictions have held up well in the T2T-CHM13 assembly.

ADDITIONAL PEER-REVIEWED PUBLICATIONS

Rhie A‡, Nurk S‡, Cechova M‡, Hoyt SJ‡, Taylor DJ‡, Altemose N, The Telomere-To-Telomere Consortium (80 authors), Phillippy AM (2023). The complete sequence of a human Y chromosome. Nature, https://doi.org/10.1038/s41586-023-06457-y [open-access preprint available]

Nurk S‡, Koren S‡, Rhie A‡, Rautiainen M‡, Bzikadze AV, Mikheenko A, Vollger MR, Altemose N, Uralsky L, Gershman A, Aganezov S, Hoyt SJ, Diekhans M, Logsdon GA, The Telomere-To-Telomere Consortium (74 authors), Surti U, McCoy RC, Dennis MY, Alexandrov IA, Gerton JL, O’Neill RJ, Timp W, Zook JM, Schatz MC, Eichler EE, Miga KH, Phillippy AM (2022). The complete sequence of a human genome. Science, 375, eabj6987, https://doi.org/10.1126/science.abj6987 [free to read]

Gershman A, Sauria MEG, Guitart X, Vollger MR, Hook PW, Hoyt SJ, Jain M, Shumate A, Razaghi R, Koren S, Altemose N, Caldas GV, Logsdon GA, Rhie A, Eichler EE, Schatz MC, O’Neill RJ, Phillippy AM, Miga KH, Timp W (2022). Epigenetic patterns in a complete human genome. Science, 375, eabj5089, https://doi.org/10.1126/science.abj5089 [free to read]

Hoyt SJ, Storer JM, Hartley GA, Grady PGS, Gershman A, de Lima LG, Limouse C, Halabian R, Wojenski L, Rodriguez M, Altemose N, Rhie A, Core LJ, Gerton JL, Makalowski W, Olson D, Rosen J, Smit AFA, Straight AF, Vollger MR, Wheeler TJ, Schatz MC, Eichler EE, Phillippy AM, Timp W, Miga KH, O’Neill RJ (2022). From telomere to telomere: The transcriptional and epigenetic state of human repeat elements. Science, 375, eabk3112, https://doi.org/10.1126/science.abk3112 [free to read]

Gupta A, Shamsi F, Altemose N, Dorlhiac GF, Cypess AM, White AP, Yosef N, Patti ME, Tseng Y-H, Streets A (2022). Characterization of transcript enrichment and detection bias in single-nuclei RNA-seq for mapping of distinct human adipocyte lineages. Genome Research, 32, 242-257, https://doi.org/10.1101/gr.275509.121 [open-access preprint available]

Grist S, Geldert A, Gopal A, Su A, Balch H, Herr A, Rampazzi S, Smullin S, Starr N, Rempel D, Agarwal P, Altemose N, Chen T, Hu G, Tung M, Pillarisetti A, Robinowitz D, Shless J (2021). Current understanding of ultraviolet-C decontamination of N95 filtering facepiece respirators. Applied Biosafety, eprint. https://doi.org/10.1089/apb.20.0051 [open access]

Nakatsuka N, Patterson N, Patsopoulos N, De Jager P, Altemose N, Tandon A, Beecham AH, McCauley JL, Isobel N, Hauser S, Hafler DA, Oksenberg JR, Reich D (2020). Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans. Scientific Reports, 10, 16902. https://doi.org/10.1038/s41598-020-74035-7 [open access]

Lai A, Altemose N, White JA, Streets AM (2019). On-ratio PDMS bonding for multilayer microfluidic device fabrication. Journal of Micromechanics and Microengineering, 29(10), 107001. https://doi.org/10.1088/1361-6439/ab341e [open-access preprint available]

Williams AL, Genovese G, Dyer T, Altemose N, Truax K, Jun G, Patterson N, Myers SR, Curran JE, Duggirala R, Blangero J, Reich D, Przeworski M, on behalf of the T2D-GENES Consortium (2015). Non-crossover gene conversions show strong GC bias and unexpected clustering in humans. eLife 4. https://doi.org/10.7554/eLife.04637 [open access]

Hinch AG, Altemose N, Noor N, Donnelly P, Myers SR (2014). Recombination in the human pseudoautosomal region PAR1. PLoS Genetics 10(7), e1004503–e1004503. https://doi.org/10.1371/journal.pgen.1004503 [open access]

Miga KH, Newton Y, Jain M, Altemose N, Willard HF, Kent WJ (2014). Centromere reference models for human chromosomes X and Y satellite arrays. Genome Research 24(4), 697–707. https://doi.org/10.1101/gr.159624.113 [open access]

Genovese G, Handsaker R, Li H, Altemose N, Lindgren AM, Chambert K, Pasaniuc B, Price AL, Reich D, Morton CC, Pollak MR, Wilson JG, McCarroll SA (2013). Using population admixture to help complete maps of the human genome. Nature Genetics 45, 406-414. https://doi.org/10.1038/ng.2565 [free to read on PubMed Central]