Bioinformatics Analysis of the Potentially Functional circRNA-miRNA-mRNA Network in Breast Cancer

Objective: Breast cancer (BC) is a heterogeneous type of cancer that occurs as a result of distinct molecular alterations in breast tissue. Although there are many new developments in treatment and targeted therapy for BC in recent years, this cancer type is still the most common one among women with high morbidity and mortality. Therefore, new research is still needed for biomarker detection. Methods: GSE101124 and GSE182471 datasets were obtained from Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (circRNAs). The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used to identify the significantly dysregulated microRNAs (miRNAs) and genes considering the Prediction Analysis of Microarray (PAM50) classification. The circRNA-miRNA-gene relationship was investigated using the Cancer Specific CircRNA (v2.0) (CSCD), miRDB, miRWalk and miRTarBase databases. The circRNA-miRNA-mRNA regulatory network was constructed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation. The protein-protein interaction network was constructed by the STRING 2021 database and visualized by the Cytoscape tool (v3.9.0). Then, raw miRNA data and genes were filtered using some selection criteria according to a specific expression level in PAM50 subgroups. A bottleneck method was utilized to obtain highly interacted hub genes using cytoHubba Cytoscape plugin. The overall survival (OS) and disease-free survival (DFS) analysis were performed for these hub genes, which are detected within the miRNA and circRNA axis in our study. Results: We identified three circRNAs, three miRNAs, and eighteen candidate target genes that may play an important role in BC. In addition, it has been determined that these molecules can be useful in the classification of BC, especially in determining the basal-like breast cancer (BLBC) subtype. Conclusions: We conclude that hsa_circ_0000515/ miR-486-5p/ SDC1 axis may be an important biomarker candidate in distinguishing patients in the BLBC group, especially according to the PAM50 classification of BC.

Molecular taxonomy and description of a new species of Limnodrilus (Naididae, Clitellata, Annelida) in China

The freshwater annelid worm genus Limnodrilus, including the widely distributed L. claparedianus Ratzel, 1868, is common in Chinese freshwater ecosystems. One species, previously recognized as morphologically intermediate between L. claparedianus and the North American taxon L. cervix Brinkhurst, 1963, is here described as a new species, L. paraclaparedianus Zhou & Cui n. sp., using both molecular and traditional taxonomy. Comparisons of sequences of the Cytochrome Oxidase subunit I (COI) mtDNA in a sample of Limnodrilus species showed that the distances between species were generally higher than the divergences within them. Phylogenetic analysis of COI as well as 16S mtDNA and Internal Transcribed Spacer 2 (ITS2) nDNA confirmed that the new species is an independent lineage. Moreover, morphological differences in the prostomium, characteristics of the chaetae and internal genitalia support the separation of the species.

Comprehensive Analysis of the Immune and Prognostic Implication of TRIM8 in Breast Cancer

Background: Breast cancer remains one of most lethal illnesses for female and the most common malignancies among women, making it important to discover novel biomarkers and therapeutic targets for breast cancer. Immunotherapy has become a promising therapeutic tool for breast cancer. The role of TRIM8 in breast cancer has rarely been reported. Method: Here we identified TRIM8 expression and its potential functions on survival in patients with breast cancer using TCGA (The cancer genome atlas), GEO (Gene expression omnibus) database and METABRIC (Molecular Taxonomy of Breast Cancer International Consortium). Then, TIMER and TISIDB databases were used to investigate the correlations between TRIM8 mRNA levels and immune characteristics. Using stepwise cox regression, we established an immune prognostic signature based on five differentially expression immune-related genes (DE-IRGs). Finally, a nomogram, accompanied by a calibration curve was proposed to predict 1-, 3-, and 5-year survival for breast cancer patients. Results: We found that TRIM8 expression was dramatically lower in breast cancer tissues in comparison with normal tissues. Lower TRIM8 expression was related with worse prognosis in breast cancer. TIMER and TISIDB analysis showed that there were strong correlations between TRIM8 expression and immune characteristics. The receiver operating characteristic (ROC) curve confirmed the good performance in survival prediction, showing good accuracy of the immune prognostic signature. We demonstrated the model usefulness of predictions by nomogram and calibration curves. Our findings indicated that TRIM8 might be a potential link between progression and prognosis survival of breast cancer.Conclusion: This is a comprehensive study to reveal that TRIM8 may serve as a potential prognostic biomarker associating with immune characteristics and provide a novel therapeutic target for the treatment of breast cancer.

Chromosomal-Level Assembly of Antarctic Scaly Rockcod, Trematomus loennbergii Genome Using Long-Read Sequencing and Chromosome Conformation Capture (Hi-C) Technologies

Trematomus species (suborder Notothenioidei; family Nototheniidae) are widely distributed in the southern oceans near Antarctica. There are 11 recognized species in the genus Trematomus, and notothenioids are known to have high chromosomal diversity (2n = 24–58) because of relatively recent and rapid adaptive radiation. Herein, we report the chromosomal-level genome assembly of T. loennbergii, the first characterized genome representative of the genus Trematomus. The final genome assembly of T. loennbergii was obtained using a Pacific Biosciences long-read sequencing platform and high-throughput chromosome conformation capture technology. Twenty-three chromosomal-level scaffolds were assembled to 940 Mb in total size, with a longest contig size of 48.5 Mb and contig N50 length of 24.7 Mb. The genome contained 42.03% repeat sequences, and a total of 24,525 protein-coding genes were annotated. We produced a high-quality genome assembly of T. loennbergii. Our results provide a first reference genome for the genus Trematomus and will serve as a basis for studying the molecular taxonomy and evolution of Antarctic fish.

African-specific prostate cancer molecular taxonomy

Prostate cancer is characterised by significant global disparity; mortality rates in Sub-Saharan Africa are double to quadruple those in Eurasia1. Hypothesising unknown interplay between genetic and non-genetic factors, tumour genome profiling envisages contributing mutational processes2,3. Through whole-genome sequencing of treatment-naïve prostate cancer from 183 ethnically/globally distinct patients (African versus European), we generate the largest cancer genomics resource for Sub-Saharan Africa. Identifying ~2 million somatic variants, Africans carried the greatest burden. We describe a new molecular taxonomy using all mutational types and ethno-geographic identifiers, including Asian. Defined as Global Mutational Subtypes (GMS) A–D, although Africans presented within all subtypes, we found GMS-B to be ‘African-specific’ and GMS-D ‘African-predominant’, including Admixed and European Africans. Conversely, Europeans from Australia, Africa and Brazil predominated within ‘mutationally-quiet’ and ethnically/globally ‘universal’ GMS-A, while European Australians shared a higher mutational burden with Africans in GMS-C. GMS predicts clinical outcomes; reconstructing cancer timelines suggests four evolutionary trajectories with different mutation rates (GMS-A, low 0.968/year versus D, highest 1.315/year). Our data suggest both common genetic factors across extant populations and regional environmental factors contributing to carcinogenesis, analogous to gene-environment interaction defined here as a different effect of an environmental surrounding in persons with different ancestries or vice versa. We anticipate GMS acting as a proxy to intrinsic and extrinsic mutational processes in cancers, promoting global inclusion in landmark studies.

Hybrid de novo genome-reassembly reveals new insights on pathways and pathogenicity determinants in rice blast pathogen Magnaporthe oryzae RMg_Dl

Blast disease incited by Magnaporthe oryzae is a major threat to sustain rice production in all rice growing nations. The pathogen is widely distributed in all rice paddies and displays rapid aerial transmissions, and seed-borne latent infection. In order to understand the genetic variability, host specificity, and molecular basis of the pathogenicity-associated traits, the whole genome of rice infecting Magnaporthe oryzae (Strain RMg_Dl) was sequenced using the Illumina and PacBio (RSII compatible) platforms. The high-throughput hybrid assembly of short and long reads resulted in a total of 375 scaffolds with a genome size of 42.43 Mb. Furthermore, comparative genome analysis revealed 99% average nucleotide identity (ANI) with other oryzae genomes and 83% against M. grisea, and 73% against M. poe genomes. The gene calling identified 10,553 genes with 10,539 protein-coding sequences. Among the detected transposable elements, the LTR/Gypsy and Type LINE showed high occurrence. The InterProScan of predicted protein sequences revealed that 97% protein family (PFAM), 98% superfamily, and 95% CDD were shared among RMg_Dl and reference 70-15 genome, respectively. Additionally, 550 CAZymes with high GH family content/distribution and cell wall degrading enzymes (CWDE) such endoglucanase, beta-glucosidase, and pectate lyase were also deciphered in RMg_Dl. The prevalence of virulence factors determination revealed that 51 different VFs were found in the genome. The biochemical pathway such as starch and sucrose metabolism, mTOR signaling, cAMP signaling, MAPK signaling pathways related genes were identified in the genome. The 49,065 SNPs, 3267 insertions and 3611 deletions were detected, and majority of these varinats were located on downstream and upstream region. Taken together, the generated information will be useful to develop a specific marker for diagnosis, pathogen surveillance and tracking, molecular taxonomy, and species delineation which ultimately leads to device improved management strategies for blast disease.

First report of the L1014F kdr mutation in wild populations of Anopheles arabiensis in Cabo Verde, West Africa

Background Due to the lack of vaccines, malaria control mainly involves the control of anopheline vectors (Anopheles spp.) using chemical insecticides. However, the prolonged and indiscriminate use of these compounds has led to the emergence of resistance in Anopheles populations in Africa. Insecticide resistance surveillance programs are less frequent in Cabo Verde than in other African countries. This study aimed to investigate the circulation of the L1014F and L1014S alleles in natural populations of Anopheles arabiensis collected from two sampling sites in the city of Praia, Cabo Verde. Methods Anopheles larvae were collected from the two sampling sites and reared in the laboratory until the adult stage. Mosquitoes were first morphologically identified by classical taxonomy and then by molecular species identification using molecular markers. All Anopheles arabiensis were subjected to PCR analysis to screen for mutations associated to resistance in the Nav gene. Results A total of 105 mosquitoes, all belonging to the Anopheles gambiae complex, were identified by classical taxonomy as well as by molecular taxonomy. Molecular identification showed that 100% of the An. gambiae senso lato specimens analyzed corresponded to An. arabiensis. Analysis of the Nav gene revealed the presence of L1014S and L1014F alleles with frequencies of 0.10 and 0.19, respectively. Conclusions Our data demonstrated, for the first time, the presence of the L1014F allele in the An. arabiensis population from Cabo Verde, as well as an increase in the frequency of the kdr L1014S allele reported in a previous study. The results of this study demonstrate the need to establish new approaches in vector control programs in Cabo Verde. Graphical Abstract

Revisit the Cellular Transmission and Emerging Techniques in Understanding the Mechanisms of Proteinopathies

Alzheimer’s and Parkinson’s diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in mediating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

Mutational landscape of high-grade B-cell lymphoma with MYC-, BCL2 and/or BCL6 rearrangements characterized by whole-exome sequencing

High-grade B-cell lymphoma accompanied with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) poses a cytogenetically-defined provisional entity among aggressive B-cell lymphomas that is traditionally associated with unfavorable prognosis. To better understand the mutational and molecular landscape of HGBL-DH/TH we here performed whole-exome-sequencing and deep panel next-generation-sequencing (NGS) of 47 clinically annotated cases. Oncogenic drivers, mutational signatures and perturbed pathways were compared with data from follicular lymphoma (FL), diffuse large-B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We find an accumulation of oncogenic mutations in NOTCH, IL6/JAK/STAT and NFκB signaling pathways and delineate the mutational relationship within the continuum between FL/DLBCL, HGBL-DH/TH and BL. Further, we provide evidence of a molecular divergence between BCL2 and BCL6 rearranged HGBL-DH. Beyond a significant congruency with the C3/EZB DLBCL cluster in BCL2 rearranged cases on an exome-wide level, we observe an enrichment of the SBS6 mutation signature in BCL6 rearranged cases. Differential gene set enrichment and subsequent network propagation analysis according to cytogenetically defined subgroups revealed an impairment of TP53 and MYC pathway signaling in BCL2 rearranged cases, whereas BCL6 rearranged cases lacked this enrichment, but instead showed impairment of E2F targets. Intriguingly, HGBL-TH displayed intermediate mutational features in all three aspects. This study elucidates a recurrent pattern of mutational events driving FL into MYC-driven BCL2 rearranged HGBL, unveiling the mutational pathogenesis of this provisional entity. Through this refinement of the molecular taxonomy for aggressive, germinal-center derived B-cell lymphomas, this calls into question the current WHO-classification system, especially regarding the status of MYC/BCL6 rearranged HGBL.