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DriverPower: Combined burden and functional impact tests for cancer driver discovery [article]

Shimin Shuai, Steven Gallinger, Lincoln D. Stein
2017 bioRxiv   pre-print
We describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify cancer driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1,373 genomic features derived from public sources, DriverPower's background mutation model explains up to 93% of the regional variance in the mutation rate across a variety of tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of
more » ... iver discovery. Testing across a collection of 2,583 cancer genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Group, DriverPower has the highest F1-score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
doi:10.1101/215244 fatcat:uuo6t5rd4jg4nniguscxczrfxy

Recovery of Low Permeability Reservoirs Considering Well Shut-Ins and Surfactant Additivities

Shuai Li, Jun Tang, Yunhong Ding, Shimin Liu, Guangfeng Liu, Bo Cai
2017 Energies  
To investigate the mechanism whereby well shut-ins and surfactant additivities can increase hydrocarbon output after hydraulic fracturing, in this paper, we simulated well shut-ins with one end open (OEO) rock samples and performed a serious of imbibition experiments with different surfactant additivities based on contact angle (CA) and interfacial tension (IFT) measurements. Scanning electron microscope (SEM) and nuclear magnetic resonance (NMR) methods were also been adopted in the detection
more » ... efore and after shut-ins. The results demonstrated that cationic surfactants result in better improving oil recovery (IOR) performance due to their high wettability alteration ability on vertical fracture faces, while different kinds of surfactants have a similar ability in lowering IFT. As for shut-ins duration, the NMR transverse relaxation time (T 2 ) spectrum move towards the left side, indicating that aqueous phases migrate to smaller pores spaces and deeper distances. Aqueous migration during the shut-ins period can remove near-fracture trapped water, while surfactant additivities can accelerate and enhance this process, and these two points are the most direct reasons for the observed hydrocarbon output increases.
doi:10.3390/en10091279 fatcat:im2v4m2xj5g3xe22om3rskaofq

Combined burden and functional impact tests for cancer driver discovery using DriverPower

Shimin Shuai, PCAWG Drivers and Functional Interpretation Working Group, Steven Gallinger, Lincoln Stein, PCAWG Consortium
2020 Nature Communications  
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic
more » ... derived from public sources, DriverPower's background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
doi:10.1038/s41467-019-13929-1 pmid:32024818 pmcid:PMC7002750 fatcat:nkchtg6cgrdcznoj4kh6wd5vza

Recurrent noncoding regulatory mutations in pancreatic ductal adenocarcinoma

Michael E Feigin, Tyler Garvin, Peter Bailey, Nicola Waddell, David K Chang, David R Kelley, Shimin Shuai, Steven Gallinger, John D McPherson, Sean M Grimmond, Ekta Khurana, Lincoln D Stein (+3 others)
2017 Nature Genetics  
et al. 2017. "Recurrent noncoding regulatory mutations in pancreatic ductal adenocarcinoma." Nature genetics 49 (6): 825-833.
doi:10.1038/ng.3861 pmid:28481342 pmcid:PMC5659388 fatcat:aprdwtt7pbfzzey3yz5sqvoyse

RTKN-1/Rhotekin shields endosome-associated F-actin from disassembly to ensure endocytic recycling

Yanling Yan, Shuai Liu, Can Hu, Chaoyi Xie, Linyue Zhao, Shimin Wang, Wenjuan Zhang, Zihang Cheng, Jinghu Gao, Xin Fu, Zhenrong Yang, Xianghong Wang (+3 others)
2021 Journal of Cell Biology  
Cargo sorting and the subsequent membrane carrier formation require a properly organized endosomal actin network. To better understand the actin dynamics during endocytic recycling, we performed a genetic screen in C. elegans and identified RTKN-1/Rhotekin as a requisite to sustain endosome-associated actin integrity. Loss of RTKN-1 led to a prominent decrease in actin structures and basolateral recycling defects. Furthermore, we showed that the presence of RTKN-1 thwarts the actin disassembly
more » ... ompetence of UNC-60A/cofilin. Consistently, in RTKN-1–deficient cells, UNC-60A knockdown replenished actin structures and alleviated the recycling defects. Notably, an intramolecular interaction within RTKN-1 could mediate the formation of oligomers. Overexpression of an RTKN-1 mutant form that lacks self-binding capacity failed to restore actin structures and recycling flow in rtkn-1 mutants. Finally, we demonstrated that SDPN-1/Syndapin acts to direct the recycling endosomal dwelling of RTKN-1 and promotes actin integrity there. Taken together, these findings consolidated the role of SDPN-1 in organizing the endosomal actin network architecture and introduced RTKN-1 as a novel regulatory protein involved in this process.
doi:10.1083/jcb.202007149 pmid:33844824 fatcat:py3gpwo6vbh7bgaqspabr5shoi

Reversible lysine acetylation is involved in DNA replication initiation by regulating activities of initiator DnaA in Escherichia coli

Qiufen Zhang, Aiping Zhou, Shuxian Li, Jinjing Ni, Jing Tao, Jie Lu, Baoshan Wan, Shuai Li, Jian Zhang, Shimin Zhao, Guo-Ping Zhao, Feng Shao (+1 others)
2016 Scientific Reports  
Supplementary methods Genetic Procedures Gene cloning and plasmid construction The genomic DNA of E. coli was extracted using Easy-DNA kit (Invitrogen, Carlsbad, CA). The genes mentioned in this manuscript were amplified with the corresponding primers listed in Table S2 using the E. coli MG1655 genomic DNA as template. The PCR products were digested with the corresponding restriction enzyme and then cloned into the vectors. Generation of the deletion mutants of target genes Mutants with
more » ... s of the target genes including yfiQ, cobB and ackA mutant were constructed by the method described by Datsenko and Wanner 1 . Briefly, parental E. coli strain was transformed with the pKD46 vector, which contains genes coding for the arabinose-induced λ Red recombinase system that promotes recombination between linear pieces of DNA (PCR product) and the host chromosome. This recombination is based on short stretches of homology (50 nucleotides) on the linear DNA to the site of recombination. The 5' ends of the primers used for amplification of the PCR product (KO F and KO R primers) contain 50-nucleotide stretches homologous to the target gene, while the 3' ends of the primers include regions homologous to the antibiotics resistance cassette on the pKD3 or pKD4 plasmid. Each PCR product was amplified, gel extracted, and electroporated into competent strain containing pKD46 prepared with the presence of arabinose. The deletion mutants were verified by PCR using primers adjacent to the gene region (CHK F and CHK R primers) and sequencing of the PCR products. Site-directed mutagenesis of dnaA 2 Site-directed mutagenesis of dnaA was performed with the corresponding primers (Table S2) , using KOD-Plus-Mutagenesis Kit according to the manufacturer's recommendations (Toyobo, SMK-101). The resulting gene mutations were confirmed by DNA sequencing. Biochemical Procedures DnaA antibody preparation The DnaA protein tagged with hexahistidine (6XHis) was overexpressed using pET22b-dnaA in E. coli strain BL21. The tagged protein was purified by nickel affinity chromatography under 8 M urea denaturing conditions and used to immunize rabbits for the production of antibodies. ChIP assay DNA fragments bound to DnaA were immunoprecipitated as described previously with some modifications 2,3 . The extracts were firstly incubated with 3% protein-A Sepharose beads for 1 h at 4°C and then were incubated with 6 μg DnaA antibody for 4.5 h at 4°C . At last, the extracts were incubated with 3% protein-A Sepharose beads for 1 h at 4°C . The amount oriC in input DNA and immunoprecipitated DNA were analyzed by real-time quantitative PCR. The ratio of ChIP value to Input value (ChIP/Input) for ylcC was subtracted from the ChIP/Input value for oriC to calculate the value for specific DnaA binding. In addition, the amount of ter DNA product in input DNA was quantified by real-time quantitative PCR using the ter RT F and ter RT R primers, and was used to calculate the oriC/ter ratio 3 . Western blot analysis Western blot was carried out by following standard procedures. Briefly, Proteins were resolved on 10% SDS-PAGE, transferred to PVDF membranes. For acetylation Western blot, 50 mM Tris-HCl (pH 7.5) with100 mM NaCl, 10% (V/V) Tween-20 and 1% peptone (Amresco, Solon, OH, USA) was used for blocking. 50 mM Tris-HCl (pH 7.5) with100 mM NaCl and 0.1% peptone was used to prepare primary and secondary antibodies. 50 mM Tris-HCl (pH 7.5) with 150 mM NaCl, 0.5% (V/V) Tween-20 and 5% skim milk was used for anti-DnaA and anti-His tag Western blot. Blots were scanned with G: BOX Chemi system (Syngene, Cambridge, UK), and the relative band intensities were quantified with Image J software. Purification of YfiQ and CobB YfiQ and CobB were overexpressed and purified by the similar procedure. BL21/pET28a-yfiQ and BL21/pET28a-cobB were induced by final concentrations of 0.1 mM IPTG at OD600 = 0.6
doi:10.1038/srep30837 pmid:27484197 pmcid:PMC4971506 fatcat:yjcsfjm57rhvbmirp4ioivkj6m

Candidate cancer driver mutations in super-enhancers and long-range chromatin interaction networks [article]

Lina Wadi, Liis Uuskula-Reimand, Keren Isaev, Shimin Shuai, Vincent Huang, Minggao Liang, Drew Thompson, Yao Li, Luyao Ruan, Marta Paczkowska, Michal Krassowski, Irakli Dzneladze (+10 others)
2017 bioRxiv   pre-print
Further, cancer types with at least three mutated samples , NBR 41 , OncoDriveFML 42 and DriverPower[Shuai & Stein] that use distinct statistical models, clustering of mutations, and functional impact  ... 
doi:10.1101/236802 fatcat:ynvislx6y5fgrlwqajeacctahq

Effects of two different selenium fertilizers on accumulation of selenium and heavy metals in rice grains in field trials

Menglan LIU, Wenlei CAO, Peng GAO, Jianhua ZHAO, Usamayounas MUHAMMAD, Shen NI, Yuanyuan ZHOU, Shuai WANG, Feng PEI, Zezhou ZHANG, Linxi YUAN, Zhangmin WANG (+6 others)
2022 Food Science and Technology  
Selenium (Se) is a nutritionally important micronutrient for humans. The use of Se fertilizers is often the most feasible approach to precisely increase Se contents in rice grains, but the effects of common commercial Se fertilizers on producing Se-rich rice remain to be investigated. In this study, we compared the effects of liquid and granular Se fertilizers on the accumulation of Se and heavy metals in rice grains of four different varieties in field. Results showed that Se accumulation in
more » ... ce grains was affected by the form of fertilizers, applied concentrations of Se fertilizers, and rice varieties. Liquid fertilizer displayed significantly higher Se transfer efficiency than granular fertilizer, whereas the granular fertilizer had a slightly higher effect on organic Se accumulation. More than 95.5% Se in grains were organic Se, with selenomethionine (SeMet) being the dominant one. The proportion of organic selenocysteine (SeCys2) in grains was significantly higher in treatments with liquid fertilizer. Both forms of fertilizers significantly reduced the accumulation of cadmium, lead, and arsenic. Collectively, our study provides a reference for producing Se-rich rice in a more competitive manner in practice.
doi:10.1590/fst.117521 fatcat:bfcqqep6snhvviba2447m6fuhy

Clinicopathological characterization of chronic lymphocytic leukemia with MYD88 mutations: L265P and non-L265P mutations are associated with different features

Wen Shuai, Pei Lin, Paolo Strati, Keyur P. Patel, Mark J. Routbort, Shimin Hu, Peng Wei, Joseph D. Khoury, M. James You, Sanam Loghavi, Zhenya Tang, Hong Fang (+3 others)
2020 Blood Cancer Journal  
MYD88 mutations in chronic lymphocytic leukemia (CLL) are not well characterized. Earlier reports yielded conflicting results in terms of clinicopathologic presentation and prognostic impact of MYD88 mutations in CLL patients. In addition, the morphological and immunophenotypic features of CLL cases carrying MYD88 mutations have not been explored. Finally, the clinical or biologic implications of the canonical L265P MYD88 mutation vs. mutations in other sites of MYD88 within the context of CLL
more » ... re also unknown. In this study, a cohort of 1779 CLL patients underwent mutational analysis, and 56 (3.1%) cases were found to have MYD88 mutations, including 38 with L265P mutations (designated here as group A) and 18 with non-L265P mutations (group B). Cases with wild type MYD88 were included as controls. There was no morphological difference in cases with and without MYD88 mutations. Immunophenotypically, cases with mutated MYD88 (both groups A and B) more frequently had an atypical immunophenotype when compared to wild type cases. Group A patients were younger and were associated with variable favorable prognostic factors, including less elevated β2-microglobulin level, negative CD38 and ZAP70, higher frequency of mutated IGHV and isolated del(13q14.3), and lower frequency of del(11q22.3) and mutations of NOTCH1 and SF3B1. In contrast, group B patients were more similar to CLL patients with wild type MYD88. There was no difference in time to first treatment when comparing MYD88-mutated vs. wild type CLL patients before and after stratification according to IGHV mutation status. In summary, MYD88 mutations are uncommon in CLL and cases with L265P mutation have distinctive clinical, immunophenotypic, cytogenetic, and molecular features. There is no significant impact of MYD88 mutations on time to first treatment in CLL.
doi:10.1038/s41408-020-00351-w pmid:32848129 fatcat:oxi7fwizrbhehleywuqoeimdlq

Combined burden and functional impact tests for cancer driver discovery using DriverPower

Shimin Shuai, Steven Gallinger, Lincoln Stein
2020
The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic
more » ... derived from public sources, DriverPower's background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.
doi:10.7892/boris.146115 fatcat:4frqfofemngjzele5vhnj4xdpu

Donkey genomes provide new insights into domestication and selection for coat color

Changfa Wang, Haijing Li, Yu Guo, Jinming Huang, Yan Sun, Jiumeng Min, Jinpeng Wang, Xiaodong Fang, Zicheng Zhao, Shuai Wang, Yanlin Zhang, Qingfeng Liu (+38 others)
2020 Nature Communications  
AbstractCurrent knowledge about the evolutionary history of donkeys is still incomplete due to the lack of archeological and whole-genome diversity data. To fill this gap, we have de novo assembled a chromosome-level reference genome of one male Dezhou donkey and analyzed the genomes of 126 domestic donkeys and seven wild asses. Population genomics analyses indicate that donkeys were domesticated in Africa and conclusively show reduced levels of Y chromosome variability and discordant paternal
more » ... nd maternal histories, possibly reflecting the consequences of reproductive management. We also investigate the genetic basis of coat color. While wild asses show diluted gray pigmentation (Dun phenotype), domestic donkeys display non-diluted black or chestnut coat colors (non-Dun) that were probably established during domestication. Here, we show that the non-Dun phenotype is caused by a 1 bp deletion downstream of the TBX3 gene, which decreases the expression of this gene and its inhibitory effect on pigment deposition.
doi:10.1038/s41467-020-19813-7 pmid:33293529 fatcat:wfymsnhcdzgodbdmoqyrjgz33y

Table of contents

2020 IEEE Wireless Communications Letters  
Bin Lyu, Dinh Thai Hoang, Shimin Gong, Dusit Niyato, and Dong In Kim 1663 Joint-Mapping-Based Variable Active Antenna Spatial Modulation . . . . . . . . . . .  ...  Shuai Huang, Lin Lin, Juan Xu, Weisi Guo, and Hao Yan 1682 Low-Complexity Leakage-Based Secure Precise Wireless Transmission With Hybrid Beamforming . . . . . . . . . . . . . . . . . . . . . . . . . .  ... 
doi:10.1109/lwc.2020.3023753 fatcat:7ixhcfulvfgczbpbx5fph6jd3a

Discovery and characterization of coding and non-coding driver mutations in more than 2,500 whole cancer genomes [article]

Esther Rheinbay, Morten Muhlig Nielsen, Federico Abascal, Grace Tiao, Henrik Hornshøj, Julian M Hess, Randi Istrup Istrup Pedersen, Lars Feuerbach, Radhakrishnan Sabarinathan, Henrik Tobias Madsen, JAEGIL KIM, Loris Mularoni (+61 others)
2017 bioRxiv   pre-print
DriverPower (Shimin Shuai) DriverPower is a combined burden and functional impact test for coding and non-coding cancer driver elements.  ... 
doi:10.1101/237313 fatcat:gt5imzwlure6vojs6hd3yxmb7a

Contents

2013 2013 10th Working Conference on Mining Software Repositories (MSR)  
Maletic -Kent State University, USA . . . 169 Search-Based Duplicate Defect Detection: An Industrial Experience Mehdi Amoui, Nilam Kaushik, Abraham Al-Dabbagh, Ladan Tahvildari, Shimin Li, and Weining  ...  Saskatchewan, Canada . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 An Empirical Study of the Fault-Proneness of Clone Mutation and Clone Migration Shuai  ... 
doi:10.1109/msr.2013.6623994 fatcat:qujhmiqbknfh3gkrp7w6en2jsy

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

Esther Rheinbay, PCAWG Drivers and Functional Interpretation Working Group, Morten Muhlig Nielsen, Federico Abascal, Jeremiah A. Wala, Ofer Shapira, Grace Tiao, Henrik Hornshøj, Julian M. Hess, Randi Istrup Juul, Ziao Lin, Lars Feuerbach (+85 others)
2020 Nature  
The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver
more » ... overy that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
doi:10.1038/s41586-020-1965-x pmid:32025015 pmcid:PMC7054214 fatcat:n7bsxiodavbzreizndi3vcidxq
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