Inter-assay variability of next-generation sequencing-based gene panels

BACKGROUND: Tumor heterogeneity has been known to cause inter-assay discordance among next-generation sequencing (NGS) results. However, whether preclinical factors such as sample type, sample quality and analytical features of gene panel can affect the concordance between two different assays remains largely unexplored. METHODS: Replicate sets of DNA samples extracted from formalin-fixed paraffin-embedded tissues (FFPE) (n = 20) and fresh frozen (FF) tissues (n = 10) were herein analyzed using a tumor-only (TO) and paired tumor-normal (TN) gene panel in laboratories certified by the Clinical Laboratory Improvement Amendment. Reported variants from the TO and TN panels were then compared. Furthermore, additional FFPE samples were sequentially sliced from the same FFPE block and submitted to another TN panel assay. RESULTS: Substantial discordance (71.8%) was observed between the results of the two panels despite using identical DNA samples, with the discordance rate being significantly higher for FFPE samples (p < 0.05). Among the 99 variants reported only in the TO panel, 32.3% were consistent with germline variants, which were excluded in the TN panel, while 30.3% had an allele frequency of less than 5%, some of which were highly likely to be artificial calls. The comparison of two independent TN panel assay results from the same FFPE block also showed substantial discordance rate (55.3%). CONCLUSIONS: In the context of clinical settings, our comparative analysis revealed that inter-NGS assay discordance commonly occurred due to sample types and the different analytical features of each panel

Üsküdar mesireleri

Taha Toros Arşivi, Dosya No: 63-Salacak-Üsküdarİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

Structure near K−K^-+pp+pp threshold in the in-flight 3^3He(K−,Λp)n(K^-,\Lambda p)n reaction

To search for an S= -1 di-baryonic state which decays to $\Lambda p$, the ${\rm{}^3He}(K^-,\Lambda p)n_{missing}$ reaction was studied at 1.0 GeV/$c$. Unobserved neutrons were kinematically identified from the missing mass $M_X$ of the ${\rm{}^3He}(K^-,\Lambda p)X$ reaction in order to have a large acceptance for the $\Lambda pn$ final state. The observed $\Lambda p n$ events, distributed widely over the kinematically allowed region of the Dalitz plot, establish that the major component comes from a three nucleon absorption process. A concentration of events at a specific neutron kinetic energy was observed in a region of low momentum transfer to the $\Lambda p$. To account for the observed peak structure, the simplest S-wave pole was assumed to exist in the reaction channel, having Breit-Wigner form in energy and with a Gaussian form-factor. A minimum $\chi^2$ method was applied to deduce its mass $M_X\ =$ 2355 $^{+ 6}_{ - 8}$ (stat.) $\pm 12$ (syst.) MeV/c$^2$, and decay-width $\Gamma_X\ =$ 110 $^{+ 19}_{ - 17}$ (stat.) $\pm 27$ (syst.) MeV/c$^2$, respectively. The form factor parameter $Q_X \sim$ 400 MeV/$c$ implies that the range of interaction is about 0.5Comment: 12pages, 8 figure

Search for the K−ppK^-pp bound state via the in-flight 3He(K−,n)^3He(K^-, n) reaction

In the J-PARC E15 experiment, a K − pp search was performed via the 3 He(K − , n ) reaction at 1.0 GeV/c . A forward-going neutron is detected by a neutron counter with 15 m flight length, and decay particles from K − pp are simultaneously measured by a cylindrical detector system that surrounds a liquid 3 He target system. In March and May, 2013, we carried out the first physics data-taking with 5×109 incident kaons on the 3 He target, and we have obtained a preliminary exclusive analysis result of 3 He(K − , Λp )n reaction

A search for the K−pp bound state in the 3He(K−in-flight, n) reaction at J-PARC

We have collected the first physics data of an experimental search for the simplest kaonic nuclear bound state, " K − pp", by the 3He( K − n) reaction at J-PARC. We confirmed that our spectrometer system works as designed and observed clear peak structure composed of the quasi-elastic K − " n " → K − n and the charge-exchange K − " p " → ¯ K 0 n reactions in the forward neutron spectrum

Pole position of Λ(1405)\Lambda(1405) measured in d(K−,n)πΣd(K^-,n)\pi\Sigma reactions

We measured a set of $\pi^\pm\Sigma^\mp$, $\pi^0\Sigma^0$, and $\pi^-\Sigma^0$ invariant mass spectra below and above the $\bar{K}N$ mass threshold in $K^-$-induced reactions on deuteron. We deduced the $S$-wave $\bar{K}N\rightarrow\pi\Sigma$ and $\bar{K}N\rightarrow\bar{K}N$ scattering amplitudes in the isospin 0 channel in the framework of a $\bar{K}N$ and $\pi\Sigma$ coupled channel. We find that a resonance pole corresponding to $\Lambda(1405)$ is located at 1417.7$^{+6.0}_{-7.4}$(fitting errors)$^{+1.1}_{-1.0}$(systematic errors) + $[-26.1^{+6.0}_{-7.9}$(fitting errors)$^{+1.7}_{-2.0}$(systematic errors)]$i$ MeV/$c^2$, closer to the $\bar{K}N$ mass threshold than the value determined by the Particle Data Group.Comment: 8 pages, 5 figure

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac