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Lin W.-H.,Center for Genomics and Systems Biology | Kussell E.,Center for Genomics and Systems Biology | Kussell E.,New York University
Nucleic Acids Research | Year: 2012

Simple sequence repeats (SSRs) are indel mutational hotspots in genomes. In prokaryotes, SSR loci can cause phase variation, a microbial survival strategy that relies on stochastic, reversible on-off switching of gene activity. By analyzing multiple strains of 42 fully sequenced prokaryotic species, we measure the relative variability and density distribution of SSRs in coding regions. We demonstrate that repeat type strongly influences indel mutation rates, and that the most mutable types are most strongly avoided across genomes. We thoroughly characterize SSR density and variability as a function of N→C position along protein sequences. Using codon-shuffling algorithms that preserve amino acid sequence, we assess evolutionary pressures on SSRs. We find that coding sequences suppress repeats in the middle of proteins, and enrich repeats near termini, yielding U-shaped SSR density curves. We show that for many species this characteristic shape can be attributed to purely biophysical constraints of protein structure. In multiple cases, however, particularly in certain pathogenic bacteria, we observe over enrichment of SSRs near protein N-termini significantly beyond expectation based on structural constraints. This increases the probability that frameshifts result in non-functional proteins, revealing that these species may evolutionarily tune SSR positions in coding regions to facilitate phase variation. © 2011 The Author(s). Source

Birnbaum K.D.,Center for Genomics and Systems Biology | Kussell E.,Center for Genomics and Systems Biology | Kussell E.,New York University
Nucleic Acids Research | Year: 2011

Global gene expression measurements are increasingly obtained as a function of cell type, spatial position within a tissue and other biologically meaningful coordinates. Such data should enable quantitative analysis of the cell-type specificity of gene expression, but such analyses can often be confounded by the presence of noise. We introduce a specificity measure Spec that quantifies the information in a gene's complete expression profile regarding any given cell type, and an uncertainty measure dSpec, which measures the effect of noise on specificity. Using global gene expression data from the mouse brain, plant root and human white blood cells, we show that Spec identifies genes with variable expression levels that are nonetheless highly specific of particular cell types. When samples from different individuals are used, dSpec measures genes' transcriptional plasticity in each cell type. Our approach is broadly applicable to mapped gene expression measurements in stem cell biology, developmental biology, cancer biology and biomarker identification. As an example of such applications, we show that Spec identifies a new class of biomarkers, which exhibit variable expression without compromising specificity. The approach provides a unifying theoretical framework for quantifying specificity in the presence of noise, which is widely applicable across diverse biological systems. © 2011 The Author(s). Source

News Article
Site: http://phys.org/biology-news/

Now, researchers at NYU Abu Dhabi have developed a map of genetic changes across the genome of date palms. They have also established genetic differences between Middle Eastern and North African date palms, an important discovery that sheds light on that long elusive question. In a new paper published in Nature Communications, researchers at the Center for Genomics and Systems Biology at NYUAD have identified more than 7 million mutations or nucleotide polymorphisms that are found between date palm varieties. They have also identified genes that may be important in fruit ripening, fruit color and disease resistance in dates. The study also offers two possible explanations for the crop's origin. One suggests that contemporary date palms descend from two distinct domestication events—an early event in the Middle East, and a later one in North Africa. A second hypothesis proposes that date palms were first cultivated in the Middle East and later spread to North Africa, but somewhere along the way North African dates were crossed with a wild predecessor. The research is part of the 100 Dates! genome sequencing project led by Dorothy Schiff Professor of Genomics Michael Purugganan. The project's goal is to learn more about the traits and evolution of the date palm through analysis of the plant's genome. "The data on diversity in the genomes helps us to identify genes that may help develop better date palms," said Purugganan, who is also a professor of biology. "It also tells us how date palms evolve, and provides clues as to where date palms came from." Evidence from archeological digs suggest that the origin of domesticated dates is in the Gulf. Seeds have been found on Dalma Island, Abu Dhabi that are more than 7,000 years old. Cultivated dates seem to appear about 3,000 years later in North Africa, according to excavation of ancient sites. The team analyzed the genome of 62 varieties of date palm from 12 countries. Seventeen samples came from North Africa; 36 inhabit the Middle East; nine are native to South Asia. The work was a collaboration between NYUAD and UAE University, as well as other researchers in Dubai, Iraq, US, Syria, Tunisia, Pakistan and Qatar. The wild ancestor of the date palm is elusive, but identifying one would provide scientists with valuable information. Khaled Hazzouri, senior research scientist at NYUAD and lead author on the paper, entitled Whole genome re-sequencing of date palms yield insights into diversification of a fruit tree crop, says: "It is important to know the identity and geographic origin of the wild progenitor of a domesticated species because it will help us understand the evolutionary process underlying domestication and the nature of the genetic changes underlying domestication." Purugganan, Hazzouri, and the team also discovered a genetic mutation that causes the trees to produce either yellow or red fruit. Interestingly, the date palm shares this genetic mutation with its very distant cousin, the oil palm. These two plants are separated by approximately 60 million years of evolution, so it's surprising that genes in both species would code for the same trait. "This similarity tells us that evolution uses the same genes in different species to get the same result," Purugganan said. It's possible that information like this could be used by plant breeders to engineer date varieties that have particular traits. For example, since some varieties of date palms can live on water with high salinity, farmers who grow crops in arid terrain could plant date palm varieties suitable for that type of climate. The 100 Dates! project is still in its first phase, and there is considerable research yet to be done. The next phase will include obtaining more samples and mapping important genes, and future research will include collaborations with researchers at UAE University in Al Ain and the University of Baghdad.

Perry M.,New York University | Desplan C.,New York University | Desplan C.,Center for Genomics and Systems Biology
Science Signaling | Year: 2013

Signaling in development is not always on or off; often, distinct intensity and duration of signaling leads to distinct outcomes. This is true for receptor tyrosine kinase (RTK) signaling in many contexts, where negative feedback often plays a role. Although such negative feedback might reduce or even turn off signaling output over time, continued signaling is often maintained for proper cell fate specifi cation. In this issue, Sieglitz et al. identify a positive regulator of Rasmediated RTK signaling that they name Rau. Rau is necessary to achieve specifi c signaling intensity for the differentiation of photoreceptors and of glia that wrap axons in the developing Drosophila eye disc. Both the negative regulator Sprouty and Rau infl uence signaling through the guanosine triphosphatase Ras; specifi - cally, Rau forms a positive feedback loop important for counteracting the Sprouty negative feedback loop. © 2013 American Association for the Advancement of Science. Source

Cipriani P.G.,Center for Genomics and Systems Biology | Cipriani P.G.,New York University | Piano F.,Center for Genomics and Systems Biology | Piano F.,New York University | Piano F.,Abu Dhabi University
Methods in Cell Biology | Year: 2011

Expanding on decades of mutational analyses, numerous genome-scale RNAi screens have now been performed in C. elegans, leading to estimates that the majority of genes with essential functions that can be revealed by single-gene perturbations have already been identified in this organism. To build on this basic foundation and uncover condition-dependent or combinatorial effects of non-essential genes will require even higher-scale screening. Here we describe a method for performing high-throughput RNAi-based screens in C. elegans in liquid in 96-well plates, and we explain how to systematically test for enhancement and suppression of temperature-sensitive mutations. This chapter covers our entire set of protocols, from setting up the experiment and screening schedule, to scoring the results. The rapid acquisition of high-quality images of each experiment allows the management of a large number of samples per screening cycle and opens up new possibilities for quantitative scoring, computerized image analysis, and the ability to review results independent of the time constraints that are associated with large-scale screening. © 2011 Elsevier Inc. Source

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