We describe an effort ("Codebook") to determine the sequence specificity of 332 putative and largely uncharacterized human transcription factors (TFs), as well as 61 control TFs. Nearly 5,000 independent experiments across multiple and assays produced motifs for just over half of the putative TFs analyzed (177, or 53%), of which most are unique to a single TF. The data highlight the extensive contribution of transposable elements to TF evolution, both in and , and identify tens of thousands of conserved, base-level binding sites in the human genome.
View Article and Find Full Text PDFA DNA sequence pattern, or "motif", is an essential representation of DNA-binding specificity of a transcription factor (TF). Any particular motif model has potential flaws due to shortcomings of the underlying experimental data and computational motif discovery algorithm. As a part of the Codebook/GRECO-BIT initiative, here we evaluated at large scale the cross-platform recognition performance of positional weight matrices (PWMs), which remain popular motif models in many practical applications.
View Article and Find Full Text PDFWe present a major update of the HOCOMOCO collection that provides DNA binding specificity patterns of 949 human transcription factors and 720 mouse orthologs. To make this release, we performed motif discovery in peak sets that originated from 14 183 ChIP-Seq experiments and reads from 2554 HT-SELEX experiments yielding more than 400 thousand candidate motifs. The candidate motifs were annotated according to their similarity to known motifs and the hierarchy of DNA-binding domains of the respective transcription factors.
View Article and Find Full Text PDFThe position weight matrix, also called the position-specific scoring matrix, is the commonly accepted model to quantify the specificity of transcription factor binding to DNA. Position weight matrices are used in thousands of projects and software tools in regulatory genomics, including computational prediction of the regulatory impact of single-nucleotide variants. Yet, recently Yan et al.
View Article and Find Full Text PDFWe present ANANASTRA, https://ananastra.autosome.org, a web server for the identification and annotation of regulatory single-nucleotide polymorphisms (SNPs) with allele-specific binding events.
View Article and Find Full Text PDFHuman iPSC cell line FAMRCi010-A was generated from a patient with restrictive cardiomyopathy carrying FLNC p.Gly2011Arg genetic variant. Patient-specific peripheral blood mononuclear cells were reprogrammed using non-integrative Sendai viruses containing OCT4, SOX2, KLF4, and CMYC.
View Article and Find Full Text PDFSequence variants in gene regulatory regions alter gene expression and contribute to phenotypes of individual cells and the whole organism, including disease susceptibility and progression. Single-nucleotide variants in enhancers or promoters may affect gene transcription by altering transcription factor binding sites. Differential transcription factor binding in heterozygous genomic loci provides a natural source of information on such regulatory variants.
View Article and Find Full Text PDFThe ion-production efficiency of a newly developed singly charged ion source (SCIS) has been investigated to discuss the possibility of it being used in an isotope separation on-line system that provides C ions for heavy-ion cancer therapy with simultaneous verification of the irradiation field using positron emission tomography. The SCIS uses a low-energy hollow electron beam to produce singly charged carbon ions efficiently. To deliver sufficient C ions to the treatment room from a limited amount of C molecules, which are produced from a boron compound target and proton-beam irradiation via the B(p,n)C reaction, the SCIS must have high ion-production efficiency.
View Article and Find Full Text PDFRev Sci Instrum
November 2018
A singly charged ion source (SCIS) has been designed using a newly developed three-dimensional particle-in-cell (PIC) code. The SCIS is to be used in an isotope separation on-line (ISOL) system that provides C ions for heavy-ion cancer therapy with simultaneous verification of the dose distribution using positron emission tomography. The SCIS uses low-energy electron beams to produce singly charged carbon ions efficiently and maintain a high vacuum in the ISOL system.
View Article and Find Full Text PDFAim: To study relationship between age-associated changes of heart rate variability (HRV), telomere length (TL), and lowering of insulin sensitivity (IS).
Material And Methods: We included in this study 229 individuals aged 23‒91 years without clinical manifestations of cardiovascular and other somatic diseases. In all participants, we analyzed HRV parameters obtained at 24-hour ECG monitoring (24-h ECG) and 5 minutes ECG recordings in the supine and standing positions.
An assembly for a commercial Ga(+) liquid metal ion source in combination with an ion transportation and focusing system, a pulse high-voltage quadrupole deflector, and a beam diagnostics system has been constructed in the framework of the iThemba LABS (Cape Town, South Africa)-JINR (Dubna, Russia) collaboration. First, results on Ga(+) ion beam commissioning will be presented. Outlook of further experiments for measurements of charge breeding efficiency in the electron string ion source with the use of external injection of Ga(+) and Au(+) ion beams will be reported as well.
View Article and Find Full Text PDFRev Sci Instrum
December 2015
A (11)C molecular production/separation system (CMPS) has been developed as part of an isotope separation on line system for simultaneous positron emission tomography imaging and heavy-ion cancer therapy using radioactive (11)C ion beams. In the ISOL system, (11)CH4 molecules will be produced by proton irradiation and separated from residual air impurities and impurities produced during the irradiation. The CMPS includes two cryogenic traps to separate specific molecules selectively from impurities by using vapor pressure differences among the molecular species.
View Article and Find Full Text PDFThe type of the Electron String Ion Sources (ESIS) is considered to be the appropriate one to produce pulsed C(4+) and C(6+) ion beams for cancer therapy accelerators. In fact, the new test ESIS Krion-6T already now provides more than 10(10) C(4+) ions per pulse and about 5 × 10(9) C(6+) ions per pulse. Such ion sources could be suitable to apply at synchrotrons.
View Article and Find Full Text PDFThis article describes an investigation to determine the optimal placement of accelerometers for the purpose of detecting a range of everyday activities. The paper investigates the effect of combining data from accelerometers placed at various bodily locations on the accuracy of activity detection. Eight healthy males participated within the study.
View Article and Find Full Text PDFBackground: While it is known that the majority of pages on the World Wide Web are in English, little is known about the preferred language of users searching for health information online.
Objectives: (1) To help global and domestic publishers, for example health and food agencies, to determine the need for translation of online information from English into local languages. (2) To help these agencies determine which language(s) they should select when publishing information online in target nations and for target subpopulations within nations.