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Litter size (LS), an important economic trait in livestock, is so complicate that involves many aspects of reproduction, the underlying mechanism of which particularly in goat has always been scanty. To uncover the genetic basis of LS, the genomic sequence of Jining Gray goat groups (one famous breed for high prolificacy in China) with LS 1, 2, and 3 for firstborn was analyzed, obtaining 563.67 Gb sequence data and a total of 31,864,651 high-quality single nucleotide polymorphisms loci were identified. Particularly, the increased heterozygosity in higher LS groups, and large continuous homozygous segments associated with lower LS group had been uncovered. Through an integrated analysis of three popular methods for detecting selective sweeps (Fst, nucleotide diversity, and Tajima's D statistic), 111 selected regions and 42 genes associated with LS were scanned genome wide. The candidate genes with highest selective signatures included KIT, KCNH7, and KMT2E in LS2 and PAK1, PRKAA1, and SMAD9 in LS3 group, respectively. Meanwhile, functional terms of programmed cell death involved in cell development and regulation of insulin receptor signaling pathway were mostly enriched with 42 candidate genes, which also included reproduction related terms of steroid metabolic process and cellular response to hormone stimulus. In conclusion, our study identified novel candidate genes involving in regulation of LS in goat, which expand our understanding of genetic fundament of reproductive ability, and the novel insights regarding to LS would be potentially applied to improve reproductive performance. Copyright © 2020 Wang, Zhang, Chen, Zhang, Li, Cheng, Shen and Lei.Circulating fetal cell-free DNA (cfDNA) is generally shorter than maternal cfDNA. Size selection of shorter cfDNA in total cfDNA could significantly increase the fetal fraction, but there are few reports of using this method to decrease the false negative rate for NIPT. In this study, nine false negative cases were retrospectively analyzed by NIPT retesting and E-gel based size-selection NIPT and the fetal cfDNA fraction in maternal total cfDNA was evaluated by calculating the proportion of reads from chromosome Y. Fetal placenta karyotypes were confirmed by CNVplex assays to analysis the reasons for false negative cases. Of the 81,601 pregnancies who underwent NIPT, nine false negative cases (0.01%) were found. Of eight retested cases, two (25%) had positive NIPT retest results, and five (62.5%) had positive size-selection NIPT results. For fetal cfDNA fraction, 100% cases had improvement after size-selection NIPT compared with the initial NIPT and retest results, and the fetal cfDNA fraction growth ratio ranged from 99 to 359%. For one twin pregnancy with one T18 fetus, size selection improved the fetal cfDNA fraction to 23.10%, and successfully detected the T18 fetus in NIPT. Placental tissue analysis results for two cases indicated both had confined placental mosaicism (CPM), which was confirmed with size-selection NIPT. In conclusion, size selection can significantly enrich the fetal cfDNA fraction and decrease the false negative rate of NIPT, especially for CPM and twin pregnancies. Copyright © 2020 Xue, Zhao, Qiao, Lu, Yu and Wang.Alternative splicing alterations can contribute to human disease. The ability of an RNA-binding protein to regulate alternative splicing outcomes can be modulated by a variety of genetic and epigenetic mechanisms. In this study, we use a computational framework to investigate the roles of certain genes, termed modulators, on changing RBPs' effect on splicing regulation. A total of 1,040,254 modulator-mediated RBP-splicing interactions were identified, including 137 RBPs, 4,309 splicing events and 2,905 modulator candidates from TCGA-KIRC RNA sequencing data. Modulators function categories were defined according to the correlation changes between RBPs expression and their targets splicing outcomes. QKI, as one of the RBPs influencing the most splicing events, attracted our attention in this study 2,014 changing triplets were identified, including 1,101 modulators and 187 splicing events. Pathway enrichment analysis showed that QKI splicing targets were enriched in tight junction pathway, endocytosis and MAPK signaling pathways, all of which are highly associated with cancer development and progression. This is the first instance of a comprehensive study on how alternative splicing outcomes changes are associated with different expression level of certain proteins, even though they were regulated by the same RBP. Our work may provide a novel view on understanding alternative splicing mechanisms in kidney cancer. Copyright © 2020 Wang, Chen, Rao and Liu.Breast cancer (BC) is one of the most common tumors, leading the causes of cancer death in women. However, the pathogenesis of BC still remains unclear, and the atlas of BC-associated risk factors is far from complete. In this study, we constructed a BC-specific coordinately regulatory network (CRN) to prioritize potential BC-associated protein-coding genes (PCGs) and non-coding RNAs (ncRNAs). We integrated 813 BC sample transcriptome data from The Cancer Genome Atlas (TCGA) and eight types of regulatory relationships to construct BC-specific CRN, including 387 transcription factors (TFs), 174 microRNAs (miRNAs), 407 long non-coding RNAs (lncRNAs), and 905 PCGs. After that, the random walk with restart (RWR) method was performed on the CRN by using the known BC-associated factors as seeds, and potential BC-associated risk factors were prioritized. Tiplaxtinin order The leave-one-out cross-validation (LOOCV) was utilized on the BC-specific CRN and achieved an area under the curve (AUC) of 0.92. The performances of common CRN, common protein-protein interaction (PPI) network, and BC-specific PPI network were also evaluated, demonstrating that the context-specific CRN prioritizes BC risk factors. Functional analysis for the top 100-ranked risk factors in the candidate list revealed that these factors were significantly enriched in cancer-related functions and had significant semantic similarity with BC-related gene ontology (GO) terms. Differential expression analysis and survival analysis proved that the prioritized risk factors significantly associated with BC progression and prognosis. In total, we provided a computational method to predict reliable BC-associated risk factors, which would help improve the understanding of the pathology of BC and benefit disease diagnosis and prognosis. Copyright © 2020 Wang, Wang, Wang, Xia, Yu, Lu, Chen, Xu and Liu.