Fractal-like Distributions over the Rational Numbers in High-throughput Biological and Clinical Data

Recent developments in extracting and processing biological and clinical data are allowing quantitative approaches to studying living systems. High-throughput sequencing, expression profiles, proteomics, and electronic health records are some examples of such technologies. Extracting meaningful information from those technologies requires careful analysis of the large volumes of data they produce. In this note, we present a set of distributions that commonly appear in the analysis of such data. These distributions present some interesting features: they are discontinuous in the rational numbers, but continuous in the irrational numbers, and possess a certain self-similar (fractal-like) structure. The first set of examples which we present here are drawn from a high-throughput sequencing experiment. Here, the self-similar distributions appear as part of the evaluation of the error rate of the sequencing technology and the identification of tumorogenic genomic alterations. The other examples are obtained from risk factor evaluation and analysis of relative disease prevalence and co-mordbidity as these appear in electronic clinical data. The distributions are also relevant to identification of subclonal populations in tumors and the study of the evolution of infectious diseases, and more precisely the study of quasi-species and intrahost diversity of viral populations

On Statistical Modeling of Sequencing Noise in High Depth Data to Assess Tumor Evolution

© 2017, Springer Science+Business Media, LLC, part of Springer Nature. One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate our model with simulated exponentially expanded populations as well as data from cell line and patient sample dilution experiments, demonstrating its utility in prognosticating tumor progression. Our results may have the potential to identify significant mutations that can cause recurrence. These results are relevant in the pretreatment clinical setting to determine appropriate therapy and prepare for potential recurrence pretreatment

The ansamycin antibiotic, rifamycin SV, inhibits BCL6 transcriptional repression and forms a complex with the BCL6-BTB/POZ domain

BCL6 is a transcriptional repressor that is over-expressed due to chromosomal translocations, or other abnormalities, in ~40% of diffuse large B-cell lymphoma. BCL6 interacts with co-repressor, SMRT, and this is essential for its role in lymphomas. Peptide or small molecule inhibitors, which prevent the association of SMRT with BCL6, inhibit transcriptional repression and cause apoptosis of lymphoma cells in vitro and in vivo. In order to discover compounds, which have the potential to be developed into BCL6 inhibitors, we screened a natural product library. The ansamycin antibiotic, rifamycin SV, inhibited BCL6 transcriptional repression and NMR spectroscopy confirmed a direct interaction between rifamycin SV and BCL6. To further determine the characteristics of compounds binding to BCL6-POZ we analyzed four other members of this family and showed that rifabutin, bound most strongly. An X-ray crystal structure of the rifabutin-BCL6 complex revealed that rifabutin occupies a partly non-polar pocket making interactions with tyrosine58, asparagine21 and arginine24 of the BCL6-POZ domain. Importantly these residues are also important for the interaction of BLC6 with SMRT. This work demonstrates a unique approach to developing a structure activity relationship for a compound that will form the basis of a therapeutically useful BCL6 inhibitor

The ROD crate DAQ software framework of the ATLAS data acquisition system

In the ATLAS experiment at the LHC, the ROD Crate DAQ provides a complete software framework to implement data acquisition functionality at the boundary between the detector specific electronics and the common part of the data acquisition system. Based on a plugin mechanism, it allows selecting and using common services (like data output and data monitoring channels) and developing software to control and acquire data from detector specific modules providing the infrastructure for control, monitoring and calibration. Including also event building functionality, the ROD Crate DAQ is intended to be the main data acquisition tool for the first phase of detector commissioning. This paper presents the design, functionality and performance of the ROD Crate DAQ and its usage in the ATLAS data acquisition system and during detector tests

Aberrant somatic hypermutation in primary mediastinal large B-cell lymphoma

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Determination of CP and CPT violation parameters in the neutral kaon system using the Bell-Steinberger relation and data from the KLOE experiment

We present an improved determination of the CP and CPT violation parameters Re(epsilon) and Im(delta) based on the unitarity condition (Bell-Steinberger relation) and on recent results from the KLOE experiment. We find Re(epsilon) = (159.6 \pm 1.3)10^-5 and Im(delta) = (0.4 \pm 2.1)10^-5, consistent with no CPT violation.Comment: Submitted to JHE

Measuring the hadronic cross section via radiative return

Recently it has been demonstrated that particle factories, such as DAPHNE and PEP-II, operating at fixed center-of-mass energies, are able to measure hadronic cross sections as a function of the hadronic system energy using the raditive return. This paper is an experimental overview of the progress in this aera. Preliminary results from KLOE for the process e+e- -> \rho \gamma -> \pi+\pi-\gamma and a fit to the pion form factor are presented. Some first results from the BABAR collaboration are also shown.Comment: Invited talk presented at RADCOR/Loops and Legs 2002, Kloster Banz/Germany, September 8-13 2002, 6 pages, 2 Figures; v1: references added, typos correcte

Measurement of the branching fraction for the decay KS --> pi e nu

We present a measurement of the branching ratio BR(KS --> pi e nu) performed using the KLOE detector. KS mesons are produced in the reaction e+ e- --> phi --> KS KL at the DAFNE collider. In a sample of about 5 million KS-tagged events we find 624 +- 30 semileptonic KS decays. Normalizing to the KS --> pi+ pi- count in the same data sample, we obtain BR(KS --> pi e nu) = (6.91 +- 0.37) 10^-4, in agreement with the Standard Model expectation.Comment: 9 pages, 5 Encapsulated Postscript figures. Submitted to Phys. Lett.

Measurement of hadronic cross section and preliminary results on the pion form factor using the radiative return at DAPHNE

In the fixed energy environment of the $e^{+}e^{-}$ collider DA$\Phi$NE, KLOE can measure the cross section of the process $e^{+}e^{-} \to$ hadrons as a function of the hadronic system energy using the radiative return. At energies below 1 GeV, $e^{+}e^{-} \to \rho \to \pi^{+}\pi^{-}$ is the dominating hadronic process. We report here on the status of the analysis for the e^{+}e^{-} \to \ppg channel, which allows to obtain a preliminary measurement of the pion form factor using an integrated luminosity of $\sim73 pb^{-1}$.Comment: Invited talk at the Seventh International Workshop on Tau Lepton Physics (TAU02-WE07), Santa Cruz, Ca, USA, Sept 2002, 9 pages, LaTeX, 9 eps figure

Measurement of Gamma(phi -> eta' gamma)/Gamma(phi -> eta gamma) and the pseudoscalar mixing angle

We have measured the radiative decays phi -> eta gamma, phi ->etaprime gamma selecting pi+ pi- gamma gamma gamma final state in a sample of about 5 times 10^7 phi mesons produced at the Frascati phi factory DAFNE. We obtain Gamma(phi -> etaprime gamma)/Gamma(phi -> eta gamma)=(4.70 +- 0.47 +- 0.31) times 10^-3. From this result we derive new accurate values for the branching ratio BR(phi ->etaprime gamma) = (6.10 +- 0.61 +- 0.43) times 10^-5, and the mixing angle of pseudoscalar mesons in the flavour basis phi_P=(41.8 +1.9 -1.6) degrees.Comment: Submitted to Phys. Lett.