A widespread length-dependent splicing dysregulation in cancer.

Dysregulation of alternative splicing is a key molecular hallmark of cancer. However, the common features and underlying mechanisms remain unclear. Here, we report an intriguing length-dependent splicing regulation in cancers. By systematically analyzing the transcriptome of thousands of cancer patients, we found that short exons are more likely to be mis-spliced and preferentially excluded in cancers. Compared to other exons, cancer-associated short exons (CASEs) are more conserved and likely to encode in-frame low-complexity peptides, with functional enrichment in GTPase regulators and cell adhesion. We developed a CASE-based panel as reliable cancer stratification markers and strong predictors for survival, which is clinically useful because the detection of short exon splicing is practical. Mechanistically, mis-splicing of CASEs is regulated by elevated transcription and alteration of certain RNA binding proteins in cancers. Our findings uncover a common feature of cancer-specific splicing dysregulation with important clinical implications in cancer diagnosis and therapies.

CircRNAFisher: a systematic computational approach for de novo circular RNA identification.

Circular RNAs (circRNAs) are emerging species of mRNA splicing products with largely unknown functions. Although several computational pipelines for circRNA identification have been developed, these methods strictly rely on uniquely mapped reads overlapping back-splice junctions (BSJs) and lack approaches to model the statistical significance of the identified circRNAs. Here, we reported a systematic computational approach to identify circRNAs by simultaneously utilizing BSJ overlapping reads and discordant BSJ spanning reads to identify circRNAs. Moreover, we developed a novel procedure to estimate the P-values of the identified circRNAs. A computational cross-validation and experimental validations demonstrated that our method performed favorably compared to existing circRNA detection tools. We created a standalone tool, CircRNAFisher, to implement the method, which might be valuable to computational and experimental scientists studying circRNAs.

[Distribution of Rh blood group in 51 283 cases of inpatients and voluntary blood donors].

Objective To investigate the distribution characteristics of Rh blood group in 51 283 cases of inpatients and voluntary blood donors. Methods Micro-column gel test was used to detect RhD, RhE, Rhe, RhC, Rhc antigen in 31 818 cases of hospitalized patients and 19 465 cases of voluntary blood donors. Results There were significant differences in Rh blood type distribution between inpatients and voluntary blood donors. The mainly phenotype of Rh blood group in the inpatients were DCCee (41.64%) and DCcEe (36.58%), and Rh blood type in voluntary blood donors were DCCee (41.11%) and DCcEe (37.11%). There were noticeable differences in Rh blood group and ABO phenotype between inpatients and voluntary blood donors. The mainly phenotype of the RhD positive patients were CcEe (36.58%) and CCee (41.64%). However, the mainly phenotype of RhD negative patients were ccee (54.30%) and Ccee (30.86%). Additionally, obvious difference of Rh blood group was seen between patients in haematology department and all patients. The voluntary blood donors from different areas including Hefei, Guangzhou, Nanning and Xi'an showed significant different Rh blood group distribution. On the contrary, no obvious difference of Rh blood group was found between Xianyang and Xi'an. Conclusion The differences of Rh blood group distribution have been found in different populations, departments and areas, which make it extremely important to detect Rh blood group in clinical transfusion.

An infinite two-dimensional hybrid water-chloride network in a 4'-(furan-2-yl)-2,2':6',2''-terpyridine nickel(II) matrix.

A new complex, namely bis-[4'-(furan-2-yl)-2,2':6',2''-terpyridine]-nickel(II) dichloride deca-hydrate, [Ni(C19H13N3O)2]Cl2·10H2O, has been crystallized by solvent evaporation and characterized by single-crystal X-ray diffraction. The coordination environment of the NiII cation is distorted octa-hedral with slight deviations from an idealized geometry. The most intriguing structural feature is an infinite two-dimensional hybrid water-chloride network parallel to (011) constructed by O-H⋯O and O-H⋯Cl hydrogen bonds involving two independent chloride ions and ten independent solvent water mol-ecules with an l-shaped pattern. One of the furyl rings is disordered with a refined occupancy ratio of 0.786 (13):0.214 (13).

Computational identification of mutually exclusive transcriptional drivers dysregulating metastatic microRNAs in prostate cancer.

Androgen-ablation therapies, which are the standard treatment for metastatic prostate cancer, invariably lead to acquired resistance. Hence, a systematic identification of additional drivers may provide useful insights into the development of effective therapies. Numerous microRNAs that are critical for metastasis are dysregulated in metastatic prostate cancer, but the underlying molecular mechanism is poorly understood. We perform an integrative analysis of transcription factor (TF) and microRNA expression profiles and computationally identify three master TFs, AR, HOXC6 and NKX2-2, which induce the aberrant metastatic microRNA expression in a mutually exclusive fashion. Experimental validations confirm that the three TFs co-dysregulate a large number of metastasis-associated microRNAs. Moreover, their overexpression substantially enhances cell motility and is consistently associated with a poor clinical outcome. Finally, the mutually exclusive overexpression between AR, HOXC6 and NKX2-2 is preserved across various tissues and cancers, suggesting that mutual exclusivity may represent an intrinsic characteristic of driver TFs during tumorigenesis.