Gpr124 is essential for blood–brain barrier integrity in central nervous system disease
Chang J, Mancuso MR, Maier C, Liang X, Yuki K, Yang L, Kwong JW, Wang J, Rao V, Vallon M, Kosinski C, Zhang JJ, Mah AT, Xu L, Li L, Gholamin S, Reyes TF, Li R, Kuhnert F, Han X, Yuan J, Chiou SH, Brettman AD, Daly L, Corney DC, Cheshier SH, Shortliffe LD, Wu X, Snyder M, Chan P, Giffard RG, Chang HY, Andreasson K, Kuo CJ.
Nat Med. 2017 Apr;23(4):450-460. doi: 10.1038/nm.4309. Epub 2017 Mar 13.
Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown.


Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression.
Contrepois K, Coudereau C, Benayoun BA, Schuler N, Roux PF, Bischof O, Courbeyrette R, Carvalho C, Thuret JY, Ma Z, Derbois C, Nevers MC, Volland H, Redon CE, Bonner WM, Deleuze JF, Wiel C, Bernard D, Snyder MP, Rübe CE, Olaso R, Fenaille F, Mann C. Nat Commun. 2017 May 10;8:14995. doi: 10.1038/ncomms14995.PMID:28489069
The senescence of mammalian cells is characterized by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. Here we show that histone H2A.J, a poorly studied H2A variant found only in mammals, accumulates in human fibroblasts in senescence with persistent DNA damage.

Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice
Indumathi Chennamsetty, Michael Coronado, Kévin Contrepois,Mark P. Keller, Ivan Carcamo-Orive, John Sandin, Giovanni Fajardo, Andrew J. Whittle,Mohsen Fathzadeh, Michael Snyder, Gerald Reaven, Alan D. Attie, Daniel Bernstein, Thomas Quertermous, Joshua W. Knowles
We recently identified human N-acetyltransferase 2 (NAT2) as an insulin resistance (IR) gene. Here, we examine the cellular mechanism linking NAT2 to IR and find that Nat1 (mouse ortholog of NAT2) is co-regulated with key mitochondrial genes.

Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information
Li X, Dunn J, Salins D, Zhou G, Zhou W, Schüssler-Fiorenza Rose SM, Perelman D, Colbert E, Runge R, Rego S, Sonecha R, Datta S, McLaughlin T, Snyder MP.PLoS Biol. 2017 Jan 12;15(1):e2001402. doi: 10.1371/journal.pbio.2001402
A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease.

Association of AHSG with alopecia and mental retardation (APMR) syndrome.
Reza Sailani M, Jahanbani F, Nasiri J, Behnam M, Salehi M, Sedghi M, Hoseinzadeh M, Takahashi S, Zia A, Gruber J, Lynch JL, Lam D, Winkelmann J, Amirkiai S, Pang B, Rego S, Mazroui S, Bernstein JA, Snyder MP. Hum Genet. 2017 Jan 4. doi: 10.1007/s00439-016-1756-5. [Epub ahead of print]
Alopecia with mental retardation syndrome (APMR) is a very rare autosomal recessive condition that is associated with total or partial absence of hair from the scalp and other parts of the body as well as variable intellectual disability.

Characterization of the Dynamic Transcriptome of a Herpesvirus with Long-read Single Molecule Real-Time Sequencing.
Tombácz D, Balázs Z, Csabai Z, Moldován N, Szűcs A, Sharon D, Snyder M, Boldogkői Z.
Herpesvirus gene expression is co-ordinately regulated and sequentially ordered during productive infection. The viral genes can be classified into three distinct kinetic groups: immediate-early, early, and late classes. In this study, a massively parallel sequencing technique that is based on PacBio Single Molecule Real-time sequencing platform, was used for quantifying the poly(A) fraction of the lytic transcriptome of pseudorabies virus (PRV) throughout a 12-hour interval of productive infection on PK-15 cells.



Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers.
Gu M, Shao NY, Sa S, Li D, Termglinchan V, Ameen M, Karakikes I, Sosa G, Grubert F, Lee J, Cao A, Taylor S, Ma Y, Zhao Z, Chappell J, Hamid R, Austin ED, Gold JD, Wu JC, Snyder MP, Rabinovitch M. Cell Stem Cell. 2016 Dec 2. pii: S1934-5909(16)30266-1. doi: 10.1016/j.stem.2016.08.019. [Epub ahead of print]
In familial pulmonary arterial hypertension (FPAH), the autosomal dominant disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides modifiers that alleviate the disease. 

Single cell transcriptomics reveals unanticipated features of early hematopoietic precursors.
Yang J, Tanaka Y, Seay M, Li Z, Jin J, Garmire LX, Zhu X, Taylor A, Li W, Euskirchen G, Halene S, Kluger Y, Snyder MP, Park IH, Pan X, Weissman SM. Nucleic Acids Res. 2016 Dec 20. pii: gkw1214. doi: 10.1093/nar/gkw1214. [Epub ahead of print]
Molecular changes underlying stem cell differentiation are of fundamental interest. scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster.

A common class of transcripts with 5'-intro depletion, distinct early coding sequence features, and N1-methyladenosine modification.
Cenik C, Chua HN, Singh G, Akef A, Snyder MP, Palazzo AF, Moore MJ, Roth FP.
Introns are found in 5' untranslated regions (5'UTRs) for 35% of all human transcripts. These 5'UTR introns are not randomly distributed: genes that encode secreted, membrane-bound and mitochondrial proteins are less likely to have them. Curiously, transcripts lacking 5'UTR introns tend to harbor specific RNA sequence elements in their early coding regions.

Simul-seq: combined DNA and RNA sequencing for whole-genome and transcriptome profiling
Reuter JA, Spacek DV, Pai RK, Snyder MP. Nat Methods. 2016 Nov;13(11):953-958. doi: 10.1038/nmeth.4028. Epub 2016 Oct 10.
Paired DNA and RNA profiling is increasingly employed in genomics research to uncover molecular mechanisms of disease and to explore personal genotype and phenotype correlations. Here, we introduce Simul-seq, a technique for the production of high-quality whole-genome and transcriptome sequencing libraries from small quantities of cells or tissues.

Can heavy isotopes increase lifespan? Studies of relative abundance in various organisms reveal chemical perspectives on aging
Li X, Snyder MP.. Bioessays. 2016 Nov;38(11):1093-1101. doi: 10.1002/bies.201600040. Epub 2016 Aug 24.
Stable heavy isotopes co-exist with their lighter counterparts in all elements commonly found in biology. These heavy isotopes represent a low natural abundance in isotopic composition but impose great retardation effects in chemical reactions because of kinetic isotopic effects (KIEs).

IPSC Model oaf Pulmonary Arterial Hypertension Reveals Novel Gene Expression and Patient Specificity
Sa S, Gu M, Chappell J, Shao NY, Ameen M, Elliott KA, Li D, Grubert F, Li CG, Taylor S, Cao A, Ma Y, Fong R, Nguyen L, Wu JC, Snyder MP, Rabinovitch M. Am J Respir Crit Care Med. 2016 Oct 25. [Epub ahead of print]
RATIONALE: Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology but different causal mechanisms may reflect a need for patient-tailored therapies.

  1. Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations.
    Araya, C. L., Cenik, C., Reuter, J. A., Kiss, G., Pande, V. S., Snyder, M. P. and Greenleaf, W. J.
    (2016). Nat Genet 48(2): 117-125. PubMed PMID: 26691984; PubMed Central PMCID: PMCPMC4731297.

  2. NIH working group report-using genomic information to guide weight management: From universal to precision treatment.
    Bray, M. S., Loos, R. J., McCaffery, J. M., Ling, C., Franks, P. W., Weinstock, G. M., Snyder, M. P., Vassy, J. L., Agurs-Collins, T. and Conference Working, G.
    (2016). Obesity (Silver Spring) 24(1): 14-22. PubMed PMID: 26692578; PubMed Central PMCID: PMCPMC4689320.

  3. Can Metabolic Profiles Be Used as a Phenotypic Readout of the Genome to Enhance Precision Medicine?
    Contrepois, K., Liang, L. and Snyder, M.
    (2016).Clin Chem 62(5): 676-678. PubMed PMID: 26960666; PubMed Central PMCID: PMCPMC4851585.

  4. Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution.
    Corces, M. R., Buenrostro, J. D., Wu, B., Greenside, P. G., Chan, S. M., Koenig, J. L., Snyder, M. P., Pritchard, J. K., Kundaje, A., Greenleaf, W. J., Majeti, R. and Chang, H. Y.
    (2016). Nat Genet. PubMed PMID: 27526324.

  5. Secure cloud computing for genomic data.
    Datta, S., Bettinger, K. and Snyder, M.
    (2016). Nat Biotechnol 34(6): 588-591. PubMed PMID: 27281411.

  6. Distance from sub-Saharan Africa predicts mutational load in diverse human genomes.
    Henn, B. M., Botigue, L. R., Peischl, S., Dupanloup, I., Lipatov, M., Maples, B. K., Martin, A. R., Musharoff, S., Cann, H., Snyder, M. P., Excoffier, L., Kidd, J. M. and Bustamante, C. D.
    (2016). Proc Natl Acad Sci U S A 113(4): E440-449. PubMed PMID: 26712023; PubMed Central PMCID: PMCPMC4743782.

  7. Effects of cellular origin on differentiation of human induced pluripotent stem cell-derived endothelial cells.
    Hu, S., Zhao, M. T., Jahanbani, F., Shao, N. Y., Lee, W. H., Chen, H., Snyder, M. P. and Wu, J. C.
    (2016). JCI Insight 1(8). PubMed PMID: 27398408; PubMed Central PMCID: PMCPMC4937999.

  8. Synthetic long-read sequencing reveals intraspecies diversity in the human microbiome.
    Kuleshov, V., Jiang, C., Zhou, W., Jahanbani, F., Batzoglou, S. and Snyder, M.
    (2016). "Nat Biotechnol 34(1): 64-69. PubMed PMID: 26655498; PubMed Central PMCID: PMCPMC4884093.

  9. Genome assembly from synthetic long read clouds.
    Kuleshov, V., Snyder, M. P. and Batzoglou, S.
    (2016).Bioinformatics 32(12): i216-i224. PubMed PMID: 27307620; PubMed Central PMCID: PMCPMC4908351.

  10. Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1.
    Landegren, N., Sharon, D., Freyhult, E., Hallgren, A., Eriksson, D., Edqvist, P. H., Bensing, S., Wahlberg, J., Nelson, L. M., Gustafsson, J., Husebye, E. S., Anderson, M. S., Snyder, M. and Kampe, O.
    (2016).Sci Rep 6: 20104. PubMed PMID: 26830021; PubMed Central PMCID: PMCPMC4735587.

  11. Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance.
    Lee, S., Zhang, C., Kilicarslan, M., Piening, B. D., Bjornson, E., Hallstrom, B. M., Groen, A. K., Ferrannini, E., Laakso, M., Snyder, M., Bluher, M., Uhlen, M., Nielsen, J., Smith, U., Serlie, M. J., Boren, J. and Mardinoglu, A.
    (2016). Cell Metab 24(1): 172-184. PubMed PMID: 27345421.

  12. Concerted genomic targeting of H3K27 demethylase REF6 and chromatin-remodeling ATPase BRM in Arabidopsis.
    Li, C., Gu, L., Gao, L., Chen, C., Wei, C. Q., Qiu, Q., Chien, C. W., Wang, S., Jiang, L., Ai, L. F., Chen, C. Y., Yang, S., Nguyen, V., Qi, Y., Snyder, M. P., Burlingame, A. L., Kohalmi, S. E., Huang, S., Cao, X., Wang, Z. Y., Wu, K., Chen, X. and Cui, Y.
    (2016). Nat Genet 48(6): 687-693. PubMed PMID: 27111034.

  13. ChIA-PET2: a versatile and flexible pipeline for ChIA-PET data analysis
    Li, G., Chen, Y., Snyder, M. P. and Zhang, M. Q.
    (2016). Nucleic Acids Res. PubMed PMID: 27625391.

  14. Yeast longevity promoted by reversing aging-associated decline in heavy isotope content.
    Li, X. and Snyder, M. P.
    (2016). Npj Aging And Mechanisms Of Disease 2: 16004.

  15. Can heavy isotopes increase lifespan? Studies of relative abundance in various organisms reveal chemical perspectives on aging.
    Li, X. and Snyder, M. P.
    (2016). Bioessays. PubMed PMID: 27554342.

  16. Protein substrates of the arginine methyltransferase Hmt1 identified by proteome arrays.
    Low, J. K., Im, H., Erce, M. A., Hart-Smith, G., Snyder, M. P. and Wilkins, M. R.
    (2016).Proteomics 16(3): 465-476. PubMed PMID: 26572822.

  17. Transcriptome Profiling of Patient-Specific Human iPSC-Cardiomyocytes Predicts Individual Drug Safety and Efficacy Responses In Vitro.
    Matsa, E., Burridge, P. W., Yu, K. H., Ahrens, J. H., Termglinchan, V., Wu, H., Liu, C., Shukla, P., Sayed, N., Churko, J. M., Shao, N., Woo, N. A., Chao, A. S., Gold, J. D., Karakikes, I., Snyder, M. P. and Wu, J. C.
    (2016).Cell Stem Cell 19(3): 311-325. PubMed PMID: 27545504.

  18. The genetic predisposition to bronchopulmonary dysplasia.
    Yu, K. H., Li, J., Snyder, M., Shaw, G. M. and O'Brodovich, H. M.
    (2016). Curr Opin Pediatr 28(3): 318-323. PubMed PMID: 26963946; PubMed Central PMCID: PMCPMC4853271.

  19. Omics Profiling in Precision Oncology.
    Yu, K. H. and Snyder, M.
    (2016). Mol Cell Proteomics 15(8): 2525-2536. PubMed PMID: 27099341; PubMed Central PMCID: PMCPMC4974334.

  20. Systematic evaluation of the impact of ChIP-seq read designs on genome coverage, peak identification, and allele-specific binding detection
    Zhang, Q., Zeng, X., Younkin, S., Kawli, T., Snyder, M. P. and Keles, S.
    (2016).BMC Bioinformatics 17: 96. PubMed PMID: 26908256; PubMed Central PMCID: PMCPMC4765064.