HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine

New York City, NY, United States

HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine

New York City, NY, United States
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Afshinnekoo E.,Weill Cornell Medicine | Afshinnekoo E.,HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine | Afshinnekoo E.,New York Medical College | Ahsanuddin S.,Weill Cornell Medicine | And 5 more authors.
British Medical Bulletin | Year: 2016

Introduction or background: Crowdfunding and crowdsourcing of medical research has emerged as a novel paradigm for many biomedical disciplines to rapidly collect, process and interpret data from high-throughput and highdimensional experiments. The novelty and promise of these approaches have led to fundamental discoveries about RNA mechanisms, microbiome dynamics and even patient interpretation of test results. However, these methods require robust training protocols, uniform sampling methods and experimental rigor in order to be useful for subsequent research efforts. Executed correctly, crowdfunding and crowdsourcing can leverage public resources and engagement to generate support for scientific endeavors that would otherwise be impossible due to funding constraints and or the large number of participants needed for data collection. Sources of data: We conducted a comprehensive literature review of scientific studies that utilized crowdsourcing and crowdfunding to generate data. We also discuss our own experiences conducting citizen-science research initiatives (MetaSUB and PathoMap) in ensuring data robustness, educational outreach and public engagement. Areas of agreement: We demonstrate the efficacy of crowdsourcing mechanisms for revolutionizing microbiome and metagenomic research to better elucidate the microbial and genetic dynamics of cities around the world (as well as non-urban areas). Crowdsourced studies have been able to create an improved and unprecedented ability to monitor, design and measure changes at the microbial and macroscopic scale. Thus, the use of crowdsourcing strategies has dramatically altered certain genomics research to create global citizen-science initiatives that reveal new discoveries about the world's genetic dynamics. Areas of controversy: The effectiveness of crowdfunding and crowdsourcing is largely dependent on the study design and methodology. One point of contention for the present discussion is the validity and scientific rigor of data that are generated by non-scientists. Selection bias, limited sample sizes and limitations for scientists in enforcing standardized protocols are all challenges for those who engage in citizen-science initiatives. Growing points: Despite the aforementioned concerns, crowdsourced data allow for greater inroads into the field of personalized medicine, whereby community members take an active role in generating data about their personal and environmental health. Areas timely for developing research: Crowdsourced viral and metagenomic studies are the next step in elucidating the genomic and epigenomic characterization of urban population health. © The Author 2016.

Kolokotronis S.-O.,Fordham University | Kolokotronis S.-O.,Sackler Institute for Comparative Genomics | Foox J.,Sackler Institute for Comparative Genomics | Rosenfeld J.A.,Sackler Institute for Comparative Genomics | And 19 more authors.
Mitochondrial DNA Part B: Resources | Year: 2016

We report the extraction of a bed bug mitogenome from high-throughput sequencing projects originally focused on the nuclear genome of Cimex lectularius. The assembled mitogenome has a similar AT nucleotide composition bias found in other insects. Phylogenetic analysis of all protein-coding genes indicates that C. lectularius is clearly a member of a paraphyletic Cimicomorpha clade within the Order Hemiptera. © 2016 The Author(s).

Doktorova M.,New York Medical College | Harries D.,Fritz Haber Institute | Khelashvili G.,New York Medical College | Khelashvili G.,HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine
Physical Chemistry Chemical Physics | Year: 2017

We have recently developed a novel computational methodology (termed RSF for Real-Space Fluctuations) to quantify the bending rigidity and tilt modulus of lipid membranes from real-space analysis of fluctuations in the tilt and splay degrees of freedom as sampled in molecular dynamics (MD) simulations. In this article, we present a comprehensive study that combines results from the application of the RSF method to a wide range of lipid bilayer systems that encompass membranes of different fluidities and sizes, including lipids with saturated and unsaturated lipid tails, single and multi-component lipid systems, as well as non-standard lipids such as the four-tailed cardiolipin. By comparing the material properties calculated with the RSF method to those obtained from experimental data and from other computational methodologies, we rigorously demonstrate the validity of our approach and show its robustness. This should allow for future applications of even more complex lipidic assemblies, whose material properties are not tractable by other computational techniques. In addition, we discuss the relationship between different definitions of the tilt modulus appearing in current literature to address some important unresolved discrepancies in the field. © the Owner Societies 2017.

Giannopoulou E.,HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine | Alves P.,Yale University | Tewari A.K.,ak Center for Robotic Surgery | Gerstein M.B.,Yale University | And 6 more authors.
Cancer Research | Year: 2013

Androgen receptor signaling plays a critical role in prostate cancer pathogenesis. Yet, the regulation of androgen receptor signaling remains elusive. Even with stringent androgen deprivation therapy, androgen receptor signaling persists. Here, our data suggest that there is a complex interaction between the expression of the tumor suppressor miRNA, miR-31, and androgen receptor signaling. We examined primary and metastatic prostate cancer and found that miR-31 expression was reduced as a result of promoter hypermethylation, and importantly, the levels of miR-31 expression were inversely correlated with the aggressiveness of the disease. As the expression of androgen receptor and miR-31 was inversely correlated in the cell lines, our study further suggested that miR-31 and androgen receptor could mutually repress each other. Upregulation of miR-31 effectively suppressed androgen receptor expression through multiple mechanisms and inhibited prostate cancer growth in vivo. Notably, we found that miR-31 targeted androgen receptor directly at a site located in the coding region, which was commonly mutated in prostate cancer. In addition, miR-31 suppressed cell-cycle regulators including E2F1, E2F2, EXO1, FOXM1, and MCM2. Together, our findings suggest a novel androgen receptor regulatory mechanism mediated through miR-31 expression. The downregulation of miR-31 may disrupt cellular homeostasis and contribute to the evolution and progression of prostate cancer. We provide implications for epigenetic treatment and support clinical development of detecting miR-31 promoter methylation as a novel biomarker. © 2012 American Association for Cancer Research.

Doane A.S.,HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine | Elemento O.,HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine
Wiley Interdisciplinary Reviews: Systems Biology and Medicine | Year: 2017

Regulatory elements determine the connectivity of molecular networks and mediate a variety of regulatory processes ranging from DNA looping to transcriptional, posttranscriptional, and posttranslational regulation. This review highlights our current understanding of the different types of regulatory elements found in molecular networks with a focus on DNA regulatory elements. We highlight technical advances and current challenges for the mapping of regulatory elements at the genome-wide scale, and describe new computational methods to uncover these elements via reconstructing regulatory networks from large genomic datasets. WIREs Syst Biol Med 2017, 9:e1374. doi: 10.1002/wsbm.1374. For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Yao Y.,Rockefeller University | Yao Y.,University of Minnesota | Norris E.H.,Rockefeller University | Mason C.E.,New York Medical College | And 4 more authors.
Nature Communications | Year: 2016

Muscle-resident PDGFRβ+ cells, which include pericytes and PW1 + interstitial cells (PICs), play a dual role in muscular dystrophy. They can either undergo myogenesis to promote muscle regeneration or differentiate into adipocytes and other cells to compromise regeneration. How the differentiation and fate determination of PDGFRβ+ cells are regulated, however, remains unclear. Here, by utilizing a conditional knockout mouse line, we report that PDGFRβ+ cell-derived laminin inhibits their proliferation and adipogenesis, but is indispensable for their myogenesis. In addition, we show that laminin alone is able to partially reverse the muscle dystrophic phenotype in these mice at the molecular, structural and functional levels. Further RNAseq analysis reveals that laminin regulates PDGFRβ+ cell differentiation/fate determination via gpihbp1. These data support a critical role of laminin in the regulation of PDGFRβ+ cell stemness, identify an innovative target for future drug development and may provide an effective treatment for muscular dystrophy. © 2016, Nature Publishing Group. All rights reserved.

Maduro V.,U.S. National Institutes of Health | Pusey B.N.,U.S. National Institutes of Health | Cherukuri P.F.,U.S. National Institutes of Health | Atkins P.,University of British Columbia | And 21 more authors.
Orphanet Journal of Rare Diseases | Year: 2016

Background: Mutations of TCF4, which encodes a basic helix-loop-helix transcription factor, cause Pitt-Hopkins syndrome (PTHS) via multiple genetic mechanisms. TCF4 is a complex locus expressing multiple transcripts by alternative splicing and use of multiple promoters. To address the relationship between mutation of these transcripts and phenotype, we report a three-generation family segregating mild intellectual disability with a chromosomal translocation disrupting TCF4. Results: Using whole genome sequencing, we detected a complex unbalanced karyotype disrupting TCF4 (46,XY,del(14)(q23.3q23.3)del(18)(q21.2q21.2)del(18)(q21.2q21.2)inv(18)(q21.2q21.2)t(14;18)(q23.3;q21.2)(14pter®14q23.3::18q21.2®18q21.2::18q21.1®18qter;18pter®18q21.2::14q23.3®14qter). Subsequent transcriptome sequencing, qRT-PCR and nCounter analyses revealed that cultured skin fibroblasts and peripheral blood had normal expression of genes along chromosomes 14 or 18 and no marked changes in expression of genes other than TCF4. Affected individuals had 12-33 fold higher mRNA levels of TCF4 than did unaffected controls or individuals with PTHS. Although the derivative chromosome generated a PLEKHG3-TCF4 fusion transcript, the increased levels of TCF4 mRNA arose from transcript variants originating distal to the translocation breakpoint, not from the fusion transcript. Conclusions: Although validation in additional patients is required, our findings suggest that the dysmorphic features and severe intellectual disability characteristic of PTHS are partially rescued by overexpression of those short TCF4 transcripts encoding a nuclear localization signal, a transcription activation domain, and the basic helix-loop-helix domain. © 2016 Maduro et al.

Rosenfeld J.A.,American Museum of Natural History | Rosenfeld J.A.,Rutgers University | Reeves D.,New York Medical College | Reeves D.,HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine | And 36 more authors.
Nature Communications | Year: 2016

The common bed bug (Cimex lectularius) has been a persistent pest of humans for thousands of years, yet the genetic basis of the bed bug's basic biology and adaptation to dense human environments is largely unknown. Here we report the assembly, annotation and phylogenetic mapping of the 697.9-Mb Cimex lectularius genome, with an N50 of 971 kb, using both long and short read technologies. A RNA-seq time course across all five developmental stages and male and female adults generated 36,985 coding and noncoding gene models. The most pronounced change in gene expression during the life cycle occurs after feeding on human blood and included genes from the Wolbachia endosymbiont, which shows a simultaneous and coordinated host/commensal response to haematophagous activity. These data provide a rich genetic resource for mapping activity and density of C. lectularius across human hosts and cities, which can help track, manage and control bed bug infestations. © 2016, Nature Publishing Group. All rights reserved.

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