Agent-Based Modeling and Analysis of Cancer Evolution

Before the development of the next-generation sequencing (NGS) technology, carcinogenesis was regarded as a linear evolutionary process, driven by repeated acquisition of multiple driver mutations and Darwinian selection. However, recent cancer genome analyses employing NGS revealed the heterogeneity of mutations in the tumor, which is known as intratumor heterogeneity (ITH) and generated by branching evolution of cancer cells. In this chapter, we introduce a simulation modeling approach useful for understanding cancer evolution and ITH. We first describe agent-based modeling for simulating branching evolution of cancer cells. We next demonstrate how to fit an agent-based model to observational data from cancer genome analyses, employing approximate Bayesian computation (ABC). Finally, we explain how to characterize the dynamics of the simulation model through sensitivity analysis. We not only explain the methodologies, but also introduce exemplifying applications. For example, simulation modeling of cancer evolution demonstrated that ITH in colorectal cancer is generated by neutral evolution, which is caused by a high mutation rate and stem cell hierarchy. For cancer genome analyses, new experimental technologies are actively being developed; these will unveil various aspects of cancer evolution when combined with the simulation modeling approach

Chlamydia trachomatis infection in early neonatal period

BACKGROUND: The clinical characteristics of Chlamydia trachomatis respiratory tract infections in Japanese neonates were investigated. METHODS: Clinical, laboratory and microbiological characteristics of five infants with pneumonia due to C. trachomatis in early neonatal period were analyzed. RESULTS: Only C. trachomatis was identified in 4 infants. Both C. trachomatis and cytomegalovirus was identified in one. Wheezing, tachypnea and cyanosis were common in infants. Mothers of five infants had negative chlamydial EIAs at 20 weeks of gestation. CONCLUSIONS: We identified five cases of C. trachomatis respiratory tract infections in early neonatal period with the possibility of intrauterine infection. Targeted screening, early diagnosis, and effective treatment of perinatal and neonatal chlamydial infections seems to be necessar

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

The Hyper Suprime-Cam SSP Survey: Overview and Survey Design

Hyper Suprime-Cam (HSC) is a wide-field imaging camera on the prime focus of the 8.2m Subaru telescope on the summit of Maunakea in Hawaii. A team of scientists from Japan, Taiwan and Princeton University is using HSC to carry out a 300-night multi-band imaging survey of the high-latitude sky. The survey includes three layers: the Wide layer will cover 1400 deg$^2$ in five broad bands ($grizy$), with a $5\,\sigma$ point-source depth of $r \approx 26$. The Deep layer covers a total of 26~deg$^2$ in four fields, going roughly a magnitude fainter, while the UltraDeep layer goes almost a magnitude fainter still in two pointings of HSC (a total of 3.5 deg$^2$). Here we describe the instrument, the science goals of the survey, and the survey strategy and data processing. This paper serves as an introduction to a special issue of the Publications of the Astronomical Society of Japan, which includes a large number of technical and scientific papers describing results from the early phases of this survey.Comment: 14 pages, 7 figures, 5 tables. Corrected for a typo in the coordinates of HSC-Wide spring equatorial field in Table

Measurements of double-helicity asymmetries in inclusive J/ψJ/\psi production in longitudinally polarized p+pp+p collisions at s=510\sqrt{s}=510 GeV

We report the double helicity asymmetry, $A_{LL}^{J/\psi}$, in inclusive $J/\psi$ production at forward rapidity as a function of transverse momentum $p_T$ and rapidity $|y|$. The data analyzed were taken during $\sqrt{s}=510$ GeV longitudinally polarized $p$$+$$p$ collisions at the Relativistic Heavy Ion Collider (RHIC) in the 2013 run using the PHENIX detector. At this collision energy, $J/\psi$ particles are predominantly produced through gluon-gluon scatterings, thus $A_{LL}^{J/\psi}$ is sensitive to the gluon polarization inside the proton. We measured $A_{LL}^{J/\psi}$ by detecting the decay daughter muon pairs $\mu^+ \mu^-$ within the PHENIX muon spectrometers in the rapidity range $1.2<|y|<2.2$. In this kinematic range, we measured the $A_{LL}^{J/\psi}$ to be $0.012 \pm 0.010$~(stat)~$\pm$~$0.003$(syst). The $A_{LL}^{J/\psi}$ can be expressed to be proportional to the product of the gluon polarization distributions at two distinct ranges of Bjorken $x$: one at moderate range $x \approx 0.05$ where recent RHIC data of jet and $\pi^0$ double helicity spin asymmetries have shown evidence for significant gluon polarization, and the other one covering the poorly known small-$x$ region $x \approx 2\times 10^{-3}$. Thus our new results could be used to further constrain the gluon polarization for $x< 0.05$.Comment: 335 authors, 10 pages, 4 figures, 3 tables, 2013 data. Version accepted for publication by Phys. Rev. D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Nuclear dependence of the transverse-single-spin asymmetry for forward neutron production in polarized pp++AA collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

During 2015 the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized $p$$+$$p$ collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in $p$$+$$p$ collisions predicts only a moderate atomic-mass-number ($A$) dependence. In contrast, the asymmetries observed at RHIC in $p$$+$$A$ collisions showed a surprisingly strong $A$ dependence in inclusive forward neutron production. The observed asymmetry in $p$$+$Al collisions is much smaller, while the asymmetry in $p$$+$Au collisions is a factor of three larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed $A$ dependence.Comment: 315 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm