Enhanced performance of gene expression predictive models with protein-mediated spatial chromatin interactions.

There have been multiple attempts to predict the expression of the genes based on the sequence, epigenetics, and various other factors. To improve those predictions, we have decided to investigate adding protein-specific 3D interactions that play a significant role in the condensation of the chromatin structure in the cell nucleus. To achieve this, we have used the architecture of one of the state-of-the-art algorithms, ExPecto, and investigated the changes in the model metrics upon adding the spatially relevant data. We have used ChIA-PET interactions that are mediated by cohesin (24 cell lines), CTCF (4 cell lines), and RNAPOL2 (4 cell lines). As the output of the study, we have developed the Spatial Gene Expression (SpEx) algorithm that shows statistically significant improvements in most cell lines. We have compared ourselves to the baseline ExPecto model, which obtained a 0.82 Spearman's rank correlation coefficient (SCC) score, and 0.85, which is reported by newer Enformer were able to obtain the average correlation score of 0.83. However, in some cases (e.g. RNAPOL2 on GM12878), our improvement reached 0.04, and in some cases (e.g. RNAPOL2 on H1), we reached an SCC of 0.86.

Enhanced performance of gene expression predictive models with protein-mediated spatial chromatin interactions.

There have been multiple attempts to predict the expression of the genes based on the sequence, epigenetics, and various other factors. To improve those predictions, we have decided to investigate adding protein-specific 3D interactions that play a major role in the compensation of the chromatin structure in the cell nucleus. To achieve this, we have used the architecture of one of the state-of-the-art algorithms, ExPecto (J. Zhou et al., 2018), and investigated the changes in the model metrics upon adding the spatially relevant data. We have used ChIA-PET interactions that are mediated by cohesin (24 cell lines), CTCF (4 cell lines), and RNAPOL2 (4 cell lines). As the output of the study, we have developed the Spatial Gene Expression (SpEx) algorithm that shows statistically significant improvements in most cell lines.

FIREcaller: Detecting frequently interacting regions from Hi-C data.

Hi-C experiments have been widely adopted to study chromatin spatial organization, which plays an essential role in genome function. We have recently identified frequently interacting regions (FIREs) and found that they are closely associated with cell-type-specific gene regulation. However, computational tools for detecting FIREs from Hi-C data are still lacking. In this work, we present FIREcaller, a stand-alone, user-friendly R package for detecting FIREs from Hi-C data. FIREcaller takes raw Hi-C contact matrices as input, performs within-sample and cross-sample normalization, and outputs continuous FIRE scores, dichotomous FIREs, and super-FIREs. Applying FIREcaller to Hi-C data from various human tissues, we demonstrate that FIREs and super-FIREs identified, in a tissue-specific manner, are closely related to gene regulation, are enriched for enhancer-promoter (E-P) interactions, tend to overlap with regions exhibiting epigenomic signatures of cis-regulatory roles, and aid the interpretation or GWAS variants. The FIREcaller package is implemented in R and freely available at https://yunliweb.its.unc.edu/FIREcaller.

The Correlation of Blood Parameters with Size in Cases of Neoplastic Tumor

Purpose: This study aimed to evaluate the impact of tumor volume on platelet counts (PLT) and mean platelet volume (MPV) and involve these parameters on overall survival. Methods: It is a retrospective study of 99 patients with lung cancer (confirmed histologically or cytologically). Sixty-six patients underwent radical operating treatment and 33 patients had only biopsies ­ due to the inoperable status of tumor According to the histopathology profile: non-small cell carcinoma ­ 23%, adenocarcinoma - 23 %, squamous - 36%, small cell carcinoma -11%, carcinoid ­ 6%. The overall survival was measured from the time of surgery to last observation or death. The tumor's size was established based on information from histopathology protocol by using model for the ellipsoid (V=4/3 π r abc). Results: KM median survival time after surgery was 20 months (95% C.I. = 16­42). The survival time depends significantly on: Tumor feature, MPV (p=0.03, p=0.04). Patients with normal PLT levels have longer survival time (median: 11 months) than thrombocytosis group (9.5) (p=0.6). Following both the PLT and MPV, a change-point that is equal to approximately 18.5 cm3 (approx. 3.3 cm in diameter) stands for a segmented relationship between tumor volume and analyzed blood indicators. Conclusions: After an overstepping of the change-point of tumor volume inflammatory processes start and they are associated with poor prognosis. MPV may be a valuable biomarker for the diagnosis and follow up of various types of carcinoma.

Tolerance and efficacy of palliative radiotherapy for advanced pancreatic cancer: A retrospective analysis of single-institutional experiences.

This study was conducted to investigate hypofractionated radiotherapy (RT) in patients with locally advanced or metastatic adenocarcinoma of the pancreas. A total of 31 patients were enrolled in this study, 26 of whom had locally advanced (M0) pancreatic cancer and 5 had metastatic (M1) disease. The patients were treated with palliative RT (6-30 Gy in 1-10 fractions over a period of 1 day-2 weeks). Treatment-related toxicity was classified according to the Common Terminology Criteria for Adverse Events, version 3.0. Early mild toxicity was observed. A total of 17 patients (55%) achieved good pain control without pharmacological therapy, and 12 patients (39%) reduced their use of analgesics; in the remaining 2 patients (6%), there was no change in analgesic use. Late high-grade (>3) toxicity was not observed. The average survival time for the 31 patients was 9 months. The 1-year overall survival rate was 16%. Palliative RT was well-tolerated and was able to prolong the survival time. The majority of the patients achieved better pain control with palliative RT.