Biology subjects

Zhang, L.

Publications and source records attributed to Zhang, L..

At least 1,567 records · Page 87Linked to original sources

bioRxiv2019

OsLUGL involved in floral development through regulating auxin level and OsARFs expression in rice (Oryza sative L.)

Specification of floral organ identity is critical for floral morphology and inflorescence architecture. Floral organ identity in plants is controlled by floral homeotic A/B/C/D/E-class genes. Although multiple genes regulate floral organogenesis our understanding of the regulatory network remains fragmentary. Here, we characterized rice floral organ gene KAIKOUXIAO (KKX), mutation of which produces an uncharacteristic open hull, abnormal seed, and semi-sterility. KKX encodes a putative LEUNIG-like (LUGL) transcriptional co-repressor. OsLUGL is preferentially expressed in young panicles and its protein can interact with OsSEU, which functions were reported as an adaptor for LEUNIG. OsLUGL-OsSEU functions together as a transcriptional regulatory complex to control organ identity specification through regulation of MADS-box genes. During this process, SEP3 (such as OsMADS8) and AP1 (such as OsMADS18) serve as the DNA-binding partner of OsLUGL-OsSEU complex. Further studies indicated that OsMADS8 and OsMADS18 could bind the promoter of OsGH3-8 and regulate its expression. The altered expression of OsGH3-8 caused the increased auxin level and the decreased expression of OsARFs. Overall, our results demonstrate a possible pathway whereby OsLUGL-OsSEU-OsAP1-OsSEP3 complex as a transcriptional regulator by targeting the promoter of OsGH3-8 directly, affecting auxin level, OsARFs expression level and thereby influencing floral development. These findings provide a valuable insight into the molecular functions of OsLUGL in rice floral development. HighlightOsLUGL through forming OsLUGL-OsSEU-OsAP1-OsSEP3 complex regulate OsGH3-8 expression, and regulate auxin level and OsARFs expression indirectly. This work is a new insight to floral development molecular mechanism.

genetics↗

bioRxiv2019

A network supporting social influences in human decision-making

Humans learn from their own trial-and-error experience and from observing others. However, it remains unanswered how brain circuits compute expected values when direct learning and social learning coexist in an uncertain environment. Using a multi-player reward learning paradigm with 185 participants (39 being scanned) in real-time, we observed that individuals succumbed to the group when confronted with dissenting information, but increased their confidence when observing confirming information. Leveraging computational modeling and fMRI we tracked direct valuation through experience and vicarious valuation through observation, and their dissociable, but interacting neural representations in the ventromedial prefrontal cortex and the anterior cingulate cortex, respectively. Their functional coupling with the right temporoparietal junction representing instantaneous social information instantiated a hitherto uncharacterized social prediction error, rather than a reward prediction error, in the putamen. These findings suggest that an integrated network involving the brains reward hub and social hub supports social influence in human decision-making.

neuroscience↗

bioRxiv2019

De novo diploid genome assembly for genome-wide structural variant detection

Structural variants (SVs) in a personal genome are important but, for all practical purposes, impossible to detect comprehensively by standard short-fragment sequencing. De novo assembly, traditionally used to generate reference genomes, offers an alternative means for variant detection and phasing but has not been applied broadly to human genomes because of fundamental limitations of short-fragment approaches and high cost of long-read technologies. We here show that 10x linked-read sequencing, which has been applied to assemble human diploid genomes into high quality contigs, supports accurate SV detection. We examined variants in six de novo 10x assemblies with diverse experimental parameters from two commonly used human cell lines, NA12878 and NA24385. The assemblies are effective in detecting mid-size SVs, which were discovered by simple pairwise alignment of the assemblies contigs to the reference (hg38). Our study also shows that the accuracy of SV breakpoint at base-pair level is high, with a majority (80% for deletion and 70% for insertion) of SVs having precisely correct sizes and breakpoints (<2bp difference). Finally, setting the ancestral state of SV loci by comparing to ape orthologs allows inference of the actual molecular mechanism (insertion or deletion) causing the mutation, which in about half of cases is opposite to that of the reference-based call. Interestingly, we uncover 214 SVs that may have been maintained as polymorphisms in the human lineage since before our divergence from chimp. Overall, we show that de novo assembly of 10x linked-read data can achieve cost-effective SV detection for personal genomes.

genomics↗

bioRxiv2019

The Genetic Basis of Transcriptional and Spatial Heterogeneity of Squamous Features in Pancreatic Ductal Adenocarcinoma

Recent studies indicate that pancreatic cancer expression profiles are variable and largely reflect a classical or basal-type phenotype. We performed genetic sequencing, RNA-seq, and histologic review of multiregion sampled pancreatic cancers and found that squamous and squamoid features, indicators of poor prognosis, correlate with a "basal-like" expressional type. Cancers with squamous features were more likely to have truncal mutations in chromatin modifier genes and intercellular heterogeneity for MYC amplification that was associated with entosis. In most patients the basal phenotype coexisted with a glandular component, and phylogenetic studies indicated that it arose from a subclonal population in the tumor. These data provide a unifying paradigm for understanding the interrelationship of basal-type features, squamous histology, and somatic mutations in chromatin modifier genes in the context of the clonal evolution of pancreatic cancer.

cancer biology↗

bioRxiv2019

Impact of Prior Cancer on Outcomes in Nasopharyngeal Carcinoma

BackgroundPrior cancer is a common exclusion criterion in nasopharyngeal carcinoma (NPC) trials. However, whether a prior cancer diagnosis affects trial outcomes is still unknown. We aimed to determine the impact of prior cancer on survival in NPC. MethodsWe identified patients diagnosed with NPC between 2004 and 2009 in the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by chi-squared test and t-test as appropriate. Propensity score-adjusted Kaplan-Meier methods and Cox proportional hazard models were used to evaluate the impact of prior cancer on overall survival (OS). ResultsAmong 3,131 eligible NPC patients, 349 (11.15%) patients had a history of prior cancer. The Kaplan-Meier curves did not show a statistically significantly different OS (p=0.19). Subgroup analyses stratified by timing of prior cancer and AJCC TNM stage of index cancer displayed the same tendency, prior cancer didnt adversely affect OS compared with patients without prior cancer (p>0.05). Furthermore, in propensity score-adjusted COX models analysis, patients with prior cancer had the same/non-inferior OS (hazard ratio [HR] = 1.12, 95% confidence interval= 0.88 to 1.42). ConclusionsAmong patients with nasopharyngeal carcinoma, prior cancer does not convey an adverse effect on clinical outcomes, regardless of the timing of prior cancer and AJCC TNM stage of index cancer. Broader inclusion trial criteria could be adopted in nasopharyngeal carcinoma patients with a history of prior cancer. However, further studies are still needed to confirm.

epidemiology↗

bioRxiv2019

SCCNV: a software tool for identifying copy number variation from single-cell whole-genome sequencing

BackgroundIdentification of de novo mutations from cell populations requires single-cell whole-genome sequencing (SCWGS). Although many experimental protocols of SCWGS have been developed, few computational tools are available for downstream analysis of different types of somatic mutations, including copy number variation (CNV). ResultsWe developed SCCNV, a software tool for detecting CNVs from whole genome-amplified single cells. SCCNV is a read-depth based approach with adjustment for the whole-genome amplification bias. ConclusionsWe demonstrate its performance by analyzing data collected from most of the single-cell amplification methods, including DOP-PCR, MDA, MALBAC and LIANTI. SCCNV is freely available at https://github.com/biosinodx/SCCNV.

bioinformatics↗

bioRxiv2019

Single-cell whole-genome sequencing reveals the functional landscape of somatic mutations in B lymphocytes across the human lifespan

Introductory paragraphThe accumulation of mutations in somatic cells have been implicated as a cause of ageing since the 1950s1,2. Yet, attempts to establish a causal relationship between somatic mutations and ageing have been constrained by the lack of methods to directly identify mutational events in primary human tissues. Here we provide detailed, genome-wide mutation frequencies and spectra of human B lymphocytes from healthy individuals across the entire human lifespan, from newborns to centenarians, using a recently developed, highly accurate single-cell whole-genome sequencing method3. We found that the number of somatic mutations increases from <500 per cell in newborns to >3,000 per cell in centenarians. We discovered mutational hotspot regions, some of which, as expected, located at immunoglobulin genes associated with somatic hypermutation. B cell-specific mutation signatures were observed associated with development, ageing or somatic hypermutation (SHM). The SHM signature strongly correlated with the signature found in human chronic lymphocytic leukemia and malignant B-cell lymphomas4, indicating that even in B cells of healthy individuals the potential cancer-causing events are already present. We also identified multiple mutations in sequence features relevant to cellular function, i.e., transcribed genes and gene regulatory regions. Such mutations increased significantly during ageing, but only at approximately half the rate of the genome average, indicating selection against mutations that impact B cell function. This first full characterization of the landscape of somatic mutations in human B lymphocytes indicates that spontaneous somatic mutations accumulating with age can be deleterious and may contribute to both the increased risk for leukemia and the functional decline of B lymphocytes in the elderly.

genomics↗

bioRxiv2019

Spontaneous retrotranspositions in normal tissues are rare and associated with cell-type-specific differentiation

Activation of retrotransposons and their insertions into new genomic locations, i.e., retrotranspositions (RTs), have been identified in about 50% of tumors. However, the landscape of RTs in different, normal somatic cell types in humans remains largely unknown. Using single-cell whole-genome sequencing we identified 528 RT events, including LINE-1 (L1), and Alu, in 164 single cells and clones of fibroblasts, neurons, B lymphocytes, hepatocytes and liver stem cells, of 29 healthy human subjects aged from 0 to 106 years. The frequency of RTs was found to vary from <1 on average per cell in primary fibroblasts to 7.8 per cell in hepatocytes. Somewhat surprisingly, RT frequency does not increase with age, which is in contrast to other types of spontaneous mutation. RTs were found significantly more likely to insert in or close to target genes of the Polycomb Repressive Complex 2 (PRC2), which represses most of the genes encoding developmental regulators through H3K27me3 histone modification in embryonic stem cells. Indeed, when directly comparing RT frequency between differentiated liver hepatocytes with liver stem cells, the latter were almost devoid of RTs. These results indicate that spontaneous RTs are associated with cellular differentiation and occur, possibly, as a consequence of the transient chromatin transition of differentiation-specific genes from a transcriptionally repressed to activated state during the differentiation process.

genomics↗

bioRxiv2019

Selection for antibiotic resistance is reduced when embedded in a natural microbial community

Antibiotic resistance has emerged as one of the most pressing, global threats to public health. In single-species experiments selection for antibiotic resistance occurs at very low antibiotic concentrations. However, it is unclear how far these findings can be extrapolated to natural environments, where species are embedded within complex communities. We competed isogenic strains of Escherichia coli, differing exclusively in a single chromosomal resistance determinant, in the presence and absence of a pig fecal microbial community across a gradient of antibiotic concentration for two relevant antibiotics: gentamicin and kanamycin. We show that the minimal selective concentration was increased by more than one order of magnitude for both antibiotics when embedded in the community. We identified two general mechanisms were responsible for the increase in minimal selective concentration: an increase in the cost of resistance and a protective effect of the community for the susceptible phenotype. These findings have implications for our understanding of the evolution and selection of antibiotic resistance, and can inform future risk assessment efforts on antibiotic concentrations.

microbiology↗

bioRxiv2019

Effects of 7,8-dihydroxycoumarin on the Myelin Morphological Changes and PSD-95 Protein Expression in Balb/c Mice after Sciatic Nerve Injury

To investigate the effects of 7,8-dihydroxycoumarin on the myelin morphological changes and PSD-95 protein expression in mice with sciatic nerve injury, and to explore the relationship between PSD-95 protein and myelin regeneration after nerve myelin injury. 127 male adult Balb/c mice were selected and randomly divided into high, medium and low 7,8-dihydroxycoumarin dose groups and blank control group. Anastomosis was then carried out for the amputated right sciatic nerve, and intraperitoneal injection of 7,8-dihydroxycoumarin was applied postoperatively. At weeks 1, 2, 4 and 8 after surgery, nervous tissues from the injury side were taken for immunohistochemical Luxol Fast Blue (LFB) staining, so as to observe the morphological changes of the locally injured nerve myelin. Meanwhile, PSD-95 mRNA and protein expression were determined using real-time PCR and western blotting. The nerve myelin recovery in injury side of mice at all time points showed a definite dose-effect relationship with the dose of 7,8-dihydroxycoumarin. Moreover, 7,8-dihydroxycoumarin could inhibit the PSD-95 mRNA level and protein expression. At the same time, there was a dose-effect of the inhibition. 7,8-dihydroxycoumarin can affect nerve recovery in mice with sciatic nerve injury, which shows a definite dose-effect relationship with its dose. Besides, PSD-95 protein expression can suppress the regeneration of the injured nerve myelin.

neuroscience↗

bioRxiv2019

IFITM3 protects the heart during influenza virus infection

Influenza virus primarily targets the lungs, but dissemination and damage to heart tissue is also known to occur in severe infections. Despite this knowledge, influenza virus-induced cardiac pathogenesis and its underlying mechanisms have been difficult to study due to a lack of small animal models. In humans, polymorphisms in the gene encoding interferon-induced transmembrane protein 3 (IFITM3), an antiviral restriction factor, are associated with susceptibility to severe influenza, but whether IFITM3 deficiencies contribute to other aspects of pathogenesis, including cardiac dysfunction, is unknown. We now show that IFITM3 deficiency in a newly generated knockout (KO) mouse model exacerbates illness and mortality following influenza A virus infection. Enhanced pathogenesis correlated with increased replication of virus in the lungs, spleens, and hearts of KO mice relative to wildtype (WT) mice. IFITM3 KO mice exhibited normal cardiac function at baseline, but developed severely aberrant electrical activity upon infection, including decreased heart rate and irregular, arrhythmic RR (interbeat) intervals. In contrast, WT mice exhibited a mild decrease in heart rate without irregularity of RR intervals. Heightened cardiac virus titers and electrical dysfunction in KO animals was accompanied by increased activation of fibrotic pathways and fibrotic lesions in the heart. Our findings reveal an essential role for IFITM3 in controlling influenza virus replication and pathogenesis in heart tissue and establish IFITM3 KO mice as a powerful model to study virus-induced cardiac dysfunction.

immunology↗

bioRxiv2019

Depression and Anxiety in Healthcare Staffs in A Tertiary University Hospital in Luoyang, Henan Province: A Cross-Sectional Observational Study

Abstract ObjectiveMental health condition of medical professionals in China is under-recognized. The current study aimed to determine the prevalence of depression and anxiety among healthcare professionals and explore the potential influence factors.\n\nMethodThe study employed a cross-sectional design. All employees were surveyed in the first week of September 2017. General information included gender, age, workload, workplace violence, sleep quality and so on. Depression and anxiety were evaluated using PHQ-9 and GAD-7, respectively. SPSS 22.0 was used for data analysis. Logistic regression was conducted to explore risk factors contributed to metal health.\n\nResultsA total of 1,950 questionnaires were delivered, and 1,864 were returned with a response rate of 95.6%. The prevalence of depression and anxiety were 24.1% and 28.9%. As for workload, the average number of beds in charge per month is 65.97{+/-}95.58 beds, among which internal medicine department and surgical department endure more workloads. Though workers in ER and ICU manage fewer beds, they bear the longest nonstop working length in the previous month (19.18{+/-}10.82 h). There were 78.0% had suffered WPV in the preceding year. Staffs in ER and ICU are at higher risk to physical violence, especially doctors. Regarding to sleep quality, only 9.2% participants reported that they sleep well. Logistic regression indicated that workplace violence and sleep quality were independent risk factors for both anxiety and depression.\n\nConclusionThe current study revealed the devastating conditions of mental disorders in medical workers and associated factors. Effective interventions are necessary to improve this situation.

scientific communication and education↗

bioRxiv2019

Genomic signatures of somatic hybrid vigor due to heterokaryosis in the oomycete pathogen, Bremia lactucae.

Lettuce downy mildew caused by Bremia lactucae is the most important disease of lettuce globally. This oomycete pathogen is highly variable and has rapidly overcome resistance genes and fungicides deployed in attempts to control it. The described high-quality genome assembly of B. lactucae provides the foundation for detailed understanding of this economically important pathogen. The biotrophic nature of B. lactucae coupled with high levels of heterozygosity and the recently expanded repeat content made genome assembly challenging. The combined use of multiple read types, including synthetic long reads, single molecule sequences, and Hi-C, resulted in a high-quality, chromosome-scale, consensus assembly of this diploid organism. Phylogenetic analysis supports polyphyly in the downy mildews consistent with the biotrophic mode of pathogenesis evolving more than once in the Peronosporaceae. Flow cytometry plus resequencing of 30 field isolates as well as sexual offspring and asexual derivatives from multinucleate single sporangia demonstrated a high incidence of heterokaryosis in B. lactucae. Heterokaryons have phenotypic differences and increased fitness compared to homokaryotic derivatives. Consequently, B. lactucae exhibits somatic hybrid vigor and selection should be considered as acting on a population of nuclei within coenocytic mycelia. This provides evolutionary flexibility to the pathogen enabling rapid adaptation to different repertoires of host resistance genes and other challenges. The advantages of asexual persistence of heterokaryons may have been one of the drivers of selection that resulted in the loss of uninucleate zoospores in multiple downy mildews.

genomics↗

bioRxiv2019

Meta-analysis of targeted metabolomics data from heterogeneous biological samples provides insights into metabolite dynamics

IntroductionMass spectrometry-based metabolomics coupled to liquid chromatography, or LC-MS metabolomics, has become the most popular tool for global metabolite abundance profiling to study metabolism. However, the physicochemical complexity of metabolites poses a major challenge for reliable measurements of metabolite abundance. One way to address the issue is to use multiple chromatographic methods to capture a greater range of molecular diversity. We previously developed a tandem mass spectrometry-based label-free targeted metabolomics analysis framework coupled to two distinct chromatographic methods, reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC), with dynamic multiple reaction monitoring (dMRM) for simultaneous detection of over 200 metabolites to study core metabolic pathways. ObjectivesWe aim to analyze a large-scale heterogeneous data compendium generated from our LC-MS/MS platform with both RPLC and HILIC methods to systematically assess measurement quality in biological replicate groups and to gain insights into metabolite dynamics across different biological conditions. MethodsOur metabolomics framework was applied in a wide range of experimental systems including cancer cell lines, tumors, extracellular media, primary cells, immune cells, organoids, organs (e.g. pancreata), tissues, and sera from human and mice. We also developed computational and statistical analysis pipelines, which include hierarchical clustering, replicate-group CV analysis, correlation analysis, and case-control paired analysis. ResultsWe generated a compendium of 42 heterogeneous deidentified datasets with 635 samples using both RPLC and HILIC methods. There exist signature metabolites that correspond to heterogeneous phenotypes, involved in several metabolic pathways. The RPLC method shows overall better reproducibility than the HILIC method for most metabolites including polar amino acids. Correlation analysis reveals high confidence metabolites irrespective of experimental systems such as methionine, phenylalanine, and taurine. We also identify homocystine, reduced glutathione, and phosphoenolpyruvic acid as highly dynamic metabolites across all case-control paired samples. ConclusionsOur study is expected to serve as a resource and a reference point for a systematic analysis of label-free LC-MS/MS targeted metabolomics data in both RPLC and HILIC methods with dMRM.

bioinformatics↗

bioRxiv2018

Genome-wide association study identifies common genetic risk factors for alcohol, heroin and methamphetamine dependence

BackgroundCommon molecular and cellular foundations underlie different types of substance dependence (SD). However direct evidence for common genetic factors of SD is lacking. Here we aimed to identify specific genetic variants that are shared between alcoholism, heroin and methamphetamine dependence.\n\nMethodsWe first conducted a combined case-control genome-wide association analysis (GWAS) of 521 alcoholic, 1,026 heroin and 1,749 methamphetamine patients and 2,859 healthy controls. We then replicated the significant loci using an independent cohort (146 alcoholic, 1,045 heroin, 763 methamphetamine and 1,904 controls). Second, we examined the genetic effects of these identified SNPs on gene expression, addiction characteristics and brain images (gray and white matter). Furthermore, we investigated the effects of these genetic variants on addiction behaviors using self-administration rat models.\n\nResultsWe identified and validated four genome-wide significant loci in the combined cohorts in the discovery stage: ADH1B rs1229984 (P=6.45x10-10), ANKS1B rs2133896 (P=4.09x10-8), AGBL4 rs147247472 (P=4.30x10-8) and CTNNA2 rs10196867 (P=4.67x10-8). Association results for each dependence group showed that ADH1B rs1229984 was only associated with alcoholism, while the other three loci were associated with heroin, methamphetamine addiction and alcoholism respectively. Variants that were strongly linked to rs2133896 affected ANKS1B gene expression, heroin use frequency and interacted with heroin dependence to affect gray matter of the left calcarine and white matter of the right superior longitudinal fasciculus. In addition, the reduced anks1b expression in the ventral tegmental area increased addiction vulnerability for heroin and methamphetamine in self-administration rat models.\n\nConclusionOur findings revealed several novel genome-wide significant SNPs and genes that synchronously affected the vulnerability and phenotypes for alcoholism, heroin and MA dependence. These findings could shed light on the root cause and the generalized vulnerability for SD.

genomics↗

bioRxiv2018

The α-tubulin of Laodelphax striatellus facilitates the passage of rice stripe virus (RSV) and enhances horizontal transmission

Rice stripe virus (RSV), causal agent of rice stripe disease, is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus) in a persistent manner. The midgut and salivary glands of SBPH are the first and last barriers in viral circulation and transmission, respectively; however, the precise mechanisms used by RSV to cross these organs and re-inoculate rice have not been fully elucidated. We obtained full-length cDNA of L. striatellus -tubulin 2 (LsTUB) and found that RSV infection increased the level of LsTUB in vivo. Furthermore, LsTUB was shown to bind the RSV nonstructural protein 3 (NS3) in vitro. RNAi was used to reduce LsTUB expression, which caused a significant reduction in RSV titer, NS3 expression, RSV inoculation rates, and transmission to healthy plants. Electrical penetration graphs (EPG) showed that LsTUB knockdown by RNAi did not impact SBPH feeding; therefore, the reduction in RSV inoculation rate was likely caused by the decrease in RSV transmission. These findings suggest that LsTUB mediates the passage of RSV through midgut and salivary glands and leads to successful horizontal transmission.

pathology↗

bioRxiv2018

Robust Antibacterial Activity of Tungsten Oxide (WO3-X) Nanodots

Antibacterial agents are an important tool in the prevention of bacterial infections. Inorganic materials are attractive due to their high stability under a variety of conditions compared to organic antibacterial agents. Herein tungsten oxide nanodots (WO3-X), synthesized by a simple one-pot synthetic approach, was found to exhibit efficient antibacterial capabilities. The analyses with colony-forming units (CFU) showed excellent antibacterial activity of WO3-X against both gram-negative E. coli (Escherichia coli) and gram-positive S. aureus (Staphylococcus aureus) strains. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed clear damage to the bacterial cell membranes, which was further confirmed by molecular dynamics simulations. Additionally, exposure to simulated sunlight was found to further increase germicidal activity of WO3-X nanodots - a 30-minute exposure to sunlight (combining 50 g/mL WO3-X nanodots) showed a 70% decrease in E. coli viability compared to without exposure. Electron spin resonance spectroscopy (ESR) was used to elucidate the underlying mechanism of this photocatalytic activity through the generation of hydroxyl radical species. Cell counting kit-8 (CCK-8) and the live/dead assay were further employed to evaluate the cytotoxicity of WO3-X nanodots on eukaryotic cells, which demonstrated their general biocompatibility. In all, our results suggest WO3-X nanodots have considerable potential in antibacterial applications, while also being biocompatible at large.

pharmacology and toxicology↗

bioRxiv2018

Uncovering missed indels by leveraging unmapped reads

In current practice, Next Generation Sequencing (NGS) applications start with mapping/aligning short reads to the reference genome, with the aim of identifying genetic mutations. While most short reads can be mapped to the reference genome accurately by existing alignment tools, a significant number remain unmapped and excluded from downstream analyses thus potentially discarding important biological information hidden in the unmapped reads. This paper describes Genesis-indel, a computational pipeline that explores the unmapped reads to identify novel indels that are initially missed in the alignment procedure. Genesis-indel is applied to the unmapped reads of 30 Breast Cancer patients from TCGA. Results show that the unmapped reads are conserved between the two subtypes of breast cancer investigated in this study and might contribute to the divergence between the subtypes. Genesis-indel is able to leverage the unmapped reads to identify 72,997 small to large novel high-quality indels previously not found in the original alignments and among them, 16,141 have not been annotated in the widely used mutation database. Statistical analysis shows that these new indels mostly altered the oncogenes and tumor suppressor genes. Functional annotation further reveals that these indels are strongly correlated to pathways of cancer and can have high to moderate impact on protein functions. Additionally, these indels overlap with the genes that are missed in the indels from the originally mapped reads and contribute to the tumorigenesis in multiple carcinomas.

bioinformatics↗