Computational approaches for detecting disease-associated alternative splicing events.

Alternative splicing (AS) is a key transcriptional regulation pathway. Recent studies have shown that AS events are associated with the occurrence of complex diseases. Various computational approaches have been developed for the detection of disease-associated AS events. In this review, we first describe the metrics used for quantitative characterization of AS events. Second, we review and discuss the three types of methods for detecting disease-associated splicing events, which are differential splicing analysis, aberrant splicing detection and splicing-related network analysis. Third, to further exploit the genetic mechanism of disease-associated AS events, we describe the methods for detecting genetic variants that potentially regulate splicing. For each type of methods, we conducted experimental comparison to illustrate their performance. Finally, we discuss the limitations of these methods and point out potential ways to address them. We anticipate that this review provides a systematic understanding of computational approaches for the analysis of disease-associated splicing.

Isothermal confined pyrolysis on source rock and kerogens in the presence and absence of water: Implication in isotopic rollover in shale gases.

Isotopic rollover refers to that δ13C value of a gas component decreases with maturity. Its occurrence is closely related to high productivity of shale gas. Isothermal confined pyrolysis experiments (gold capsules) were performed to simulate this phenomenon on whole rock Lucaogou and kerogens Saergan, Wuerhe and Fengcheng in the absence (anhydrous) and presence of added water (hydrous) at 50 MPa, 372 °C and heating duration 0-672 h, corresponding to 0.96-1.85 EASY%Ro. For kerogen Saergan isolated from source rock with hydrogen index (HI) 159 mg/g TOC and 1.10-1.30% Ro equivalent, none of δ13C1, δ13C2 and δ13C3 showed any rollover in both anhydrous and hydrous experiments. For Lucaogou whole rock with HI 856 mg/g TOC and 0.50-0.60%Ro, both δ13C2 and δ13C3 showed rollover in anhydrous experiments while all δ13C1, δ13C2 and δ13C3 showed rollover with greater magnitude in hydrous experiments starting at 1.49-1.64 EASY%Ro. For kerogens Wuerhe and Fengcheng isolated from source rocks with HI of 550 and 741 mg/g TOC, and 1.18 and 0.96%Ro respectively, both δ13C2 and δ13C3 demonstrated rollover in anhydrous experiments while only δ13C2 showed rollover with minor magnitude in hydrous experiments starting at 1.47-1.53 EASY%Ro. The different effects of water on isotopic rollover among samples Lucaogou, Wuerhe and Fengcheng can be ascribed to rate related isotopic fractionation. Higher generation rate leads to minor isotopic fractionation and rollover magnitude. It was suggested that isotopic rollover likely occurs in a source rock having higher amount of initial retained oil prior to bulk oil cracking and currently within the major stage of oil-cracking to gas (1.50-2.00%Ro).