A co-localization model of paired ChIP-seq data using a large ENCODE data set enables comparison of multiple samples.

Deep sequencing approaches, such as chromatin immunoprecipitation by sequencing (ChIP-seq), have been successful in detecting transcription factor-binding sites and histone modification in the whole genome. An approach for comparing two different ChIP-seq data would be beneficial for predicting unknown functions of a factor. We propose a model to represent co-localization of two different ChIP-seq data. We showed that a meaningful overlapping signal and a meaningless background signal can be separated by this model. We applied this model to compare ChIP-seq data of RNA polymerase II C-terminal domain (CTD) serine 2 phosphorylation with a large amount of peak-called data, including ChIP-seq and other deep sequencing data in the Encyclopedia of DNA Elements (ENCODE) project, and then extracted factors that were related to RNA polymerase II CTD serine 2 in HeLa cells. We further analyzed RNA polymerase II CTD serine 7 phosphorylation, of which their function is still unclear in HeLa cells. Our results were characterized by the similarity of localization for transcription factor/histone modification in the ENCODE data set, and this suggests that our model is appropriate for understanding ChIP-seq data for factors where their function is unknown.

Implementation of the fifth link of the chain of survival concept for out-of-hospital cardiac arrest.

BACKGROUND: The American Heart Association 2010 resuscitation guidelines recommended adding a fifth link (multidisciplinary postresuscitation care in a regional center) to the previous 4 in the chain of survival concept for out-of-hospital cardiac arrest. Our study aimed to determine the effectiveness of this fifth link. METHODS AND RESULTS: This multicenter prospective cohort study involved all eligible out-of-hospital cardiac arrest patients in the Aizu region (n=1482, suburban/rural, Fukushima, Japan). Proportions of favorable neurological outcomes were evaluated before (January 2006-April 2008) and after (January 2009-December 2010) the implementation of the fifth link. After implementation, all patients were transported directly from the field to the tertiary-level hospital or secondarily from an outlying hospital to the tertiary-level hospital after restoration of circulation. The tertiary hospital provided intensive postresuscitation care, including appropriate hemodynamic and respiratory management, therapeutic hypothermia, and percutaneous coronary intervention. One-month survival with a favorable neurological outcome among all patients treated by emergency medical services providers improved significantly after implementation (4 of 770 [0.5%] versus 21 of 712 [3.0%]; P<0.001). The adjusted odds ratios of favorable neurological outcome were 0.9 (95% confidence interval, 0.7-1.1) for early access to emergency medical care, 3.1 (95% confidence interval, 0.7-14.2) for bystander resuscitation, 14.7 (95% confidence interval, 3.2-67.0) for early defibrillation, 1.0 (95% confidence interval, 1.0-1.1) for early advanced life support, and 7.8 (95% confidence interval, 1.6-39.0) for the fifth link. CONCLUSION: The proportion of out-of-hospital cardiac arrest patients with a favorable neurological outcome improved significantly after the implementation of the fifth link, which may be an independent predictor of outcome. CLINICAL TRIAL REGISTRATION: URL: http://www.apps.who.int/trialsearch. Unique identifier: UMIN000001607.