Publications by authors named "Aarti Jajoo"

4 Publications

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Edematous severe acute malnutrition is characterized by hypomethylation of DNA.

Nat Commun 2019 12 19;10(1):5791. Epub 2019 Dec 19.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Edematous severe acute childhood malnutrition (edematous SAM or ESAM), which includes kwashiorkor, presents with more overt multi-organ dysfunction than non-edematous SAM (NESAM). Reduced concentrations and methyl-flux of methionine in 1-carbon metabolism have been reported in acute, but not recovered, ESAM, suggesting downstream DNA methylation changes could be relevant to differences in SAM pathogenesis. Here, we assess genome-wide DNA methylation in buccal cells of 309 SAM children using the 450 K microarray. Relative to NESAM, ESAM is characterized by multiple significantly hypomethylated loci, which is not observed among SAM-recovered adults. Gene expression and methylation show both positive and negative correlation, suggesting a complex transcriptional response to SAM. Hypomethylated loci link to disorders of nutrition and metabolism, including fatty liver and diabetes, and appear to be influenced by genetic variation. Our epigenetic findings provide a potential molecular link to reported aberrant 1-carbon metabolism in ESAM and support consideration of methyl-group supplementation in ESAM.
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http://dx.doi.org/10.1038/s41467-019-13433-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923441PMC
December 2019

NovoGraph: Human genome graph construction from multiple long-read assemblies.

F1000Res 2018 3;7:1391. Epub 2018 Sep 3.

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20817, USA.

Genome graphs are emerging as an important novel approach to the analysis of high-throughput human sequencing data. By explicitly representing genetic variants and alternative haplotypes in a mappable data structure, they can enable the improved analysis of structurally variable and hyperpolymorphic regions of the genome. In most existing approaches, graphs are constructed from variant call sets derived from short-read sequencing. As long-read sequencing becomes more cost-effective and enables assembly for increasing numbers of whole genomes, a method for the direct construction of a genome graph from sets of assembled human genomes would be desirable. Such assembly-based genome graphs would encompass the wide spectrum of genetic variation accessible to long-read-based assembly, including large structural variants and divergent haplotypes. Here we present NovoGraph, a method for the construction of a human genome graph directly from a set of assemblies. NovoGraph constructs a genome-wide multiple sequence alignment of all input contigs and creates a graph by merging the input sequences at positions that are both homologous and sequence-identical. NovoGraph outputs resulting graphs in VCF format that can be loaded into third-party genome graph toolkits. To demonstrate NovoGraph, we construct a genome graph with 23,478,835 variant sites and 30,582,795 variant alleles from assemblies of seven ethnically diverse human genomes (AK1, CHM1, CHM13, HG003, HG004, HX1, NA19240). Initial evaluations show that mapping against the constructed graph reduces the average mismatch rate of reads from sample NA12878 by approximately 0.2%, albeit at a slightly increased rate of reads that remain unmapped.
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http://dx.doi.org/10.12688/f1000research.15895.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305223PMC
November 2019

Patient-Specific Quantitation of Mitral Valve Strain by Computer Analysis of Three-Dimensional Echocardiography: A Pilot Study.

Circ Cardiovasc Imaging 2016 Jan;9(1)

From the Echocardiography Department (S.B.Z., S.H.L., W.A.Z.) and Department of Cardiovascular and Thoracic Surgery (G.M.L.), Houston Methodist DeBakey Heart and Vascular Center, TX; Department of Cardiology, Non Invasive Cardiology Unit, Affiliated with the Leviev Heart Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (S.B.Z.); and Department of Mathematics, University of Houston, TX (J.F., A.J., J.H., R.A.).

Background: A paucity of data exists on mitral valve (MV) deformation during the cardiac cycle in man. Real-time 3-dimensional (3D) echocardiography now allows dynamic volumetric imaging of the MV, thus enabling computerized modeling of MV function directly in health and disease.

Methods And Results: MV imaging using 3D transesophageal echocardiography was performed in 10 normal subjects and 10 patients with moderate-to-severe or severe organic mitral regurgitation. Using proprietary 3D software, patient-specific models of the mitral annulus and leaflets were computed at mid- and end-systole. Strain analysis of leaflet deformation was derived from these models. In normals, mean strain intensity averaged 0.11±0.02 and was higher in the posterior leaflet than in the anterior leaflet (0.13±0.03 versus 0.10±0.02; P<0.05). Mean strain intensity was higher in patients with mitral regurgitation (0.15±0.03) than in normals (0.11±0.02; P=0.05). Higher mean strain intensity was noted for the posterior leaflet in both normal and organic valves. Regional valve analysis revealed that both anterior and posterior leaflets have the highest strain concentration in the commissural zone, and the boundary zone near the annulus and at the coaptation line, with reduced strain concentration in the central leaflet zone.

Conclusions: In normals, MV strain is higher in the posterior leaflet, with the highest strain at the commissures, annulus, and coaptation zones. Patients with organic mitral regurgitation have higher strain than normals. Three-dimensional echocardiography allows noninvasive and patient-specific quantitation of strain intensities because of MV deformations and has the potential to improve noninvasive characterization and follow-up of MV disease.
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http://dx.doi.org/10.1161/CIRCIMAGING.115.003254DOI Listing
January 2016