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

The impact of surgery resident training on the duration of tibial plateau leveling osteotomy surgery

ObjectiveTo investigate the impact of surgery resident training on surgery duration in tibial plateau leveling osteotomy (TPLO) and evaluate whether surgery duration differs with each year of residency training.Study designRetrospective medical record review.AnimalsA total of 256 client-owned dogs underwent TPLO.MethodsRecords of dogs that underwent TPLO between August 2019 and August 2022 were reviewed. The effects of the surgeon (faculty/resident) and the procedure (arthrotomy/arthroscopy) on TPLO surgery duration were examined with an analysis of variance, and geometric least squares means (GLSM) were compared. A linear mixed effects model (LMM) was fitted to quantify fixed and random effects.ResultsFour faculty surgeons performed 74 (29%) TPLOs, while 10 residents performed 182 (71%) TPLOs under the direct supervision of a faculty surgeon. All TPLOs were conducted with arthrotomy (109; 43%) or arthroscopy (147; 57%). Overall, residents (GLSM, 153 min) required 54% more surgery duration than faculty surgeons (GLSM, 99 min). Surgery duration among first-year residents (GLSM, 170 min) was 15% longer than second- (GLSM, 148 min) and third-year (GLSM, 147 min) residents, whereas the duration did not differ statistically between second- and third-year residents. Arthroscopy, meniscal tear treatment, surgery on the right stifle, and increasing patient weight were also associated with longer surgery duration.ConclusionThe duration of TPLO surgery significantly decreased after the first year of residency, but did not decrease afterward.Clinical significanceThe results will aid with resource allocation, curricula planning, and cost management associated with resident training

Subaru high-z exploration of low-luminosity quasars (SHELLQs). I. Discovery of 15 quasars and bright galaxies at 5.7 < z < 6.9

We report the discovery of 15 quasars and bright galaxies at 5.7 < z < 6.9. This is the initial result from the Subaru High-z Exploration of Low-Luminosity Quasars (SHELLQs) project, which exploits the exquisite multiband imaging data produced by the Subaru Hyper Suprime-Cam (HSC) Strategic Program survey. The candidate selection is performed by combining several photometric approaches including a Bayesian probabilistic algorithm to reject stars and dwarfs. The spectroscopic identification was carried out with the Gran Telescopio Canarias and the Subaru Telescope for the first 80 deg2 of the survey footprint. The success rate of our photometric selection is quite high, approaching 100 % at the brighter magnitudes (zAB < 23.5 mag). Our selection also recovered all the known high-z quasars on the HSC images. Among the 15 discovered objects, six are likely quasars, while the other six with interstellar absorption lines and in some cases narrow emission lines are likely bright Lyman-break galaxies. The remaining three objects have weak continua and very strong and narrow Ly alpha lines, which may be excited by ultraviolet light from both young stars and quasars. These results indicate that we are starting to see the steep rise of the luminosity function of z > 6 galaxies, compared with that of quasars, at magnitudes fainter than M1450 ~ -22 mag or zAB ~24 mag. Follow-up studies of the discovered objects as well as further survey observations are ongoing.Comment: Published in ApJ (828:26, 2016

Combined mutation of Apc, Kras and Tgfbr2 effectively drives metastasis of intestinal cancer.

金沢大学新学術創成研究機構ナノ生命科学研究所Embargo Period 12 month

Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis

クローン性造血の臨床予後への影響を解明 --遺伝子変異とコピー数異常の統合的な知見--. 京都大学プレスリリース. 2021-07-09.Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11, 234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH

Discovery of the First Low-Luminosity Quasar at z > 7

We report the discovery of a quasar at z = 7.07, which was selected from the deep multi-band imaging data collected by the Hyper Suprime-Cam (HSC) Subaru Strategic Program survey. This quasar, HSC J124353.93+010038.5, has an order of magnitude lower luminosity than do the other known quasars at z > 7. The rest-frame ultraviolet absolute magnitude is M1450 = -24.13 +/- 0.08 mag and the bolometric luminosity is Lbol = (1.4 +/- 0.1) x 10^{46} erg/s. Its spectrum in the optical to near-infrared shows strong emission lines, and shows evidence for a fast gas outflow, as the C IV line is blueshifted and there is indication of broad absorption lines. The Mg II-based black hole mass is Mbh = (3.3 +/- 2.0) x 10^8 Msun, thus indicating a moderate mass accretion rate with an Eddington ratio 0.34 +/- 0.20. It is the first z > 7 quasar with sub-Eddington accretion, besides being the third most distant quasar, known to date. The luminosity and black hole mass are comparable to, or even lower than, those measured for the majority of low-z quasars discovered by the Sloan Digital Sky Survey, and thus this quasar likely represents a z > 7 counterpart to quasars commonly observed in the low-z universe.Comment: Accepted for publication in ApJ Letter

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS

Subaru High-z Exploration of Low-luminosity Quasars (SHELLQs). X. Discovery of 35 Quasars and Luminous Galaxies at 5.7 ≤ z ≤ 7.0

The American Astronomical Society, find out more The Institute of Physics, find out more THE FOLLOWING ARTICLE ISOPEN ACCESS Subaru High-z Exploration of Low-luminosity Quasars (SHELLQs). X. Discovery of 35 Quasars and Luminous Galaxies at 5.7 ≤ z ≤ 7.0 Yoshiki Matsuoka1, Kazushi Iwasawa2, Masafusa Onoue3, Nobunari Kashikawa4,5,6, Michael A. Strauss7, Chien-Hsiu Lee8, Masatoshi Imanishi5,6, Tohru Nagao1, Masayuki Akiyama9, Naoko Asami10Show full author list Published 2019 October 3 © 2019. The American Astronomical Society. The Astrophysical Journal, Volume 883, Number 2 DownloadArticle PDF DownloadArticle ePub Figures Tables References Download PDFDownload ePub 674 Total downloads 99 total citations on Dimensions. Turn on MathJax Share this article Share this content via email Share on Facebook Share on Twitter Share on Google+ Share on Mendeley Article information Abstract We report the discovery of 28 quasars and 7 luminous galaxies at 5.7 ≤ z ≤ 7.0. This is the tenth in a series of papers from the Subaru High-z Exploration of Low-Luminosity Quasars (SHELLQs) project, which exploits the deep multiband imaging data produced by the Hyper Suprime-Cam (HSC) Subaru Strategic Program survey. The total number of spectroscopically identified objects in SHELLQs has now grown to 93 high-z quasars, 31 high-z luminous galaxies, 16 [O iii] emitters at z ~ 0.8, and 65 Galactic cool dwarfs (low-mass stars and brown dwarfs). These objects were found over 900 deg2, surveyed by HSC between 2014 March and 2018 January. The full quasar sample includes 18 objects with very strong and narrow Lyα emission, whose stacked spectrum is clearly different from that of other quasars or galaxies. While the stacked spectrum shows N v λ1240 emission and resembles that of lower-z narrow-line quasars, the small Lyα width may suggest a significant contribution from the host galaxies. Thus, these objects may be composites of quasars and star-forming galaxies