| 1. |
- Xiao, Wenming, et al.
(author)
-
Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing
- 2021
-
In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1141-1150
-
Journal article (peer-reviewed)abstract
- Recommendations are given on optimal read coverage and selection of calling algorithm to maximize the reproducibility of cancer mutation detection in whole-genome or whole-exome sequencing. Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
|
|
| 2. |
- Alipoormazandarani, Niloofar, et al.
(author)
-
Functional Lignin Nanoparticles with Tunable Size and Surface Properties : Fabrication, Characterization, and Use in Layer-by-Layer Assembly
- 2021
-
In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:22, s. 26308-26317
-
Journal article (peer-reviewed)abstract
- Lignin is the richest source of renewable aromatics and has immense potential for replacing synthetic chemicals. The limited functionality of lignin is, however, challenging for its potential use, which motivates research for creating advanced functional lignin-derived materials. Here, we present an aqueous-based acid precipitation method for preparing functional lignin nanoparticles (LNPs) from carboxy-methylated or carboxy-pentylated lignin. We observe that the longer grafted side chains of carboxy-pentylated lignin allow for the formation of larger LNPs. The functional nanoparticles have high tolerance against salt and aging time and well-controlled size distribution with R-h <= 60 nm over a pH range of 5-11. We further investigate the layer-by-layer (LbL) assembly of the LNPs and poly(allylamine hydrochloride) (PAH) using a stagnation point adsorption reflectometry (SPAR) and quartz crystal microbalance with dissipation (QCM-D). Results demonstrate that LNPs made of carboxypentylated lignin (i.e., PLNPs with the adsorbed mass of 3.02 mg/m(2)) form a more packed and thicker adlayer onto the PAH surface compared to those made of carboxymethylated lignin (i.e., CLNPs with the adsorbed mass of 2.51 mg/m(2)). The theoretical flux, J, and initial rate of adsorption, (d Gamma/dt)(0), analyses confirm that 22% of PLNPs and 20% of CLNPs arriving at the PAH surface are adsorbed. The present study provides a feasible platform for engineering LNPs with a tunable size and adsorption behavior, which can be adapted in hionanomaterial production.
|
|
| 3. |
- Wang, Chunlin, et al.
(author)
-
High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets
- 2010
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 107:4, s. 1518-1523
-
Journal article (peer-reviewed)abstract
- Developing T cells face a series of cell fate choices in the thymus and in the periphery. The role of the individual T cell receptor (TCR) in determining decisions of cell fate remains unresolved. The stochastic/selection model postulates that the initial fate of the cell is independent of TCR specificity, with survival dependent on additional TCR/coreceptor "rescue" signals. The "instructive" model holds that cell fate is initiated by the interaction of the TCR with a cognate peptide-MHC complex. T cells are then segregated on the basis of TCR specificity with the aid of critical coreceptors and signal modulators [Chan S, Correia-Neves M, Benoist C, Mathis (1998) Immunol Rev 165: 195-207]. The former would predict a random representation of individual TCR across divergent T cell lineages whereas the latter would predict minimal overlap between divergent T cell subsets. To address this issue, we have used high-throughput sequencing to evaluate the TCR distribution among key T cell developmental and effector subsets from a single donor. We found numerous examples of individual subsets sharing identical TCR sequence, supporting a model of a stochastic process of cell fate determination coupled with dynamic patterns of clonal expansion of T cells bearing the same TCR sequence among both CD4(+) and CD8+ populations.
|
|
| 4. |
- Zhou, Yali, et al.
(author)
-
Long-Term Stability of Different Kinds of Gas Nanobubbles in Deionized and Salt Water
- 2021
-
In: Materials. - : MDPI. - 1996-1944. ; 14:7
-
Journal article (peer-reviewed)abstract
- Nanobubbles have many potential applications depending on their types. The long-term stability of different gas nanobubbles is necessary to be studied considering their applications. In the present study, five kinds of nanobubbles (N2, O2, Ar + 8%H2, air and CO2) in deionized water and a salt aqueous solution were prepared by the hydrodynamic cavitation method. The mean size and zeta potential of the nanobubbles were measured by a light scattering system, while the pH and Eh of the nanobubble suspensions were measured as a function of time. The nanobubble stability was predicted and discussed by the total potential energies between two bubbles by the extended Derjaguin–Landau–Verwey–Overbeek (DLVO) theory. The nanobubbles, except CO2, in deionized water showed a long-term stability for 60 days, while they were not stable in the 1 mM (milli mol/L) salt aqueous solution. During the 60 days, the bubble size gradually increased and decreased in deionized water. This size change was discussed by the Ostwald ripening effect coupled with the bubble interaction evaluated by the extended DLVO theory. On the other hand, CO2 nanobubbles in deionized water were not stable and disappeared after 5 days, while the CO2 nanobubbles in 1 mM of NaCl and CaCl2 aqueous solution became stable for 2 weeks. The floating and disappearing phenomena of nanobubbles were estimated and discussed by calculating the relationship between the terminal velocity of the floating bubble and bubble size.
|
|
| 5. |
- Babrzadeh, Farbod, et al.
(author)
-
Whole-genome sequencing of the efficient industrial fuel-ethanol fermentative Saccharomyces cerevisiae strain CAT-1
- 2012
-
In: Molecular Genetics and Genomics. - : Springer Science and Business Media LLC. - 1617-4615 .- 1617-4623. ; 287:6, s. 485-494
-
Journal article (peer-reviewed)abstract
- The Saccharomyces cerevisiae strains widely used for industrial fuel-ethanol production have been developed by selection, but their underlying beneficial genetic polymorphisms remain unknown. Here, we report the draft whole-genome sequence of the S. cerevisiae strain CAT-1, which is a dominant fuel-ethanol fermentative strain from the sugarcane industry in Brazil. Our results indicate that strain CAT-1 is a highly heterozygous diploid yeast strain, and the similar to 12-Mb genome of CAT-1, when compared with the reference S228c genome, contains similar to 36,000 homozygous and similar to 30,000 heterozygous single nucleotide polymorphisms, exhibiting an uneven distribution among chromosomes due to large genomic regions of loss of heterozygosity (LOH). In total, 58 % of the 6,652 predicted protein-coding genes of the CAT-1 genome constitute different alleles when compared with the genes present in the reference S288c genome. The CAT-1 genome contains a reduced number of transposable elements, as well as several gene deletions and duplications, especially at telomeric regions, some correlated with several of the physiological characteristics of this industrial fuel-ethanol strain. Phylogenetic analyses revealed that some genes were likely associated with traits important for bioethanol production. Identifying and characterizing the allelic variations controlling traits relevant to industrial fermentation should provide the basis for a forward genetics approach for developing better fermenting yeast strains.
|
|
| 6. |
- Brusentsev, Yury, et al.
(author)
-
Photocross-Linkable and Shape-Memory Biomaterial Hydrogel Based on Methacrylated Cellulose Nanofibres
- 2023
-
In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 24:8, s. 3835-3845
-
Journal article (peer-reviewed)abstract
- In the context of three-dimensional (3D) cell culture and tissue engineering, 3D printing is a powerful tool for customizing in vitro 3D cell culture models that are critical for understanding the cell-matrix and cell-cell interactions. Cellulose nanofibril (CNF) hydrogels are emerging in constructing scaffolds able to imitate tissue in a microenvironment. A direct modification of the methacryloyl (MA) group onto CNF is an appealing approach to synthesize photocross-linkable building blocks in formulating CNF-based bioinks for light-assisted 3D printing; however, it faces the challenge of the low efficiency of heterogenous surface modification. Here, a multistep approach yields CNF methacrylate (CNF-MA) with a decent degree of substitution while maintaining a highly dispersible CNF hydrogel, and CNF-MA is further formulated and copolymerized with monomeric acrylamide (AA) to form a super transparent hydrogel with tuneable mechanical strength (compression modulus, approximately 5-15 kPa). The resulting photocurable hydrogel shows good printability in direct ink writing and good cytocompatibility with HeLa and human dermal fibroblast cell lines. Moreover, the hydrogel reswells in water and expands to all directions to restore its original dimension after being air-dried, with further enhanced mechanical properties, for example, Young’s modulus of a 1.1% CNF-MA/1% PAA hydrogel after reswelling in water increases to 10.3 kPa from 5.5 kPa.
|
|
| 7. |
- Duan, Suping, et al.
(author)
-
Oxygen Ions O+ Energized by Kinetic Alfven Eigenmode During Dipolarizations of Intense Substorms
- 2017
-
In: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 122:11, s. 11256-11273
-
Journal article (peer-reviewed)abstract
- Singly charged oxygen ions, O+, energized by kinetic Alfven wave eigenmode (KAWE) in the plasma sheet boundary layer during dipolarizations of two intense substorms, 10: 07 UT on 31 August 2004 and 18: 24 UT on 14 September 2004, are investigated by Cluster spacecraft in the magnetotail. It is found that after the beginning of the expansion phase of substorms, O+ ions are clearly energized in the direction perpendicular to the magnetic field with energy larger than 1 keV in the near-Earth plasma sheet during magnetic dipolarizations. The pitch angle distribution of these energetic O+ ions is significantly different from that of O+ ions with energy less than 1 keV before substorm onset that is in the quasi-parallel direction along the magnetic field. The KAWE with the large perpendicular unipolar electric field, E-z similar to -20 mV/m, significantly accelerates O+ ions in the direction perpendicular to the background magnetic field. We present good evidences that O+ ion origin from the ionosphere along the magnetic field line in the northward lobe can be accelerated in the perpendicular direction during substorm dipolarizations. The change of the move direction of O+ ions is useful for O+ transferring from the lobe into the central plasma sheet in the magnetotail. Thus, KAWE can play an important role in O+ ion transfer process from the lobe into the plasma sheet during intense substorms.
|
|
| 8. |
- Fan, Dingxun, et al.
(author)
-
Formation of long single quantum dots in high quality InSb nanowires grown by molecular beam epitaxy
- 2015
-
In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 7:36, s. 14822-14828
-
Journal article (peer-reviewed)abstract
- We report on realization and transport spectroscopy study of single quantum dots (QDs) made from InSb nanowires grown by molecular beam epitaxy (MBE). The nanowires employed are 50-80 nm in diameter and the QDs are defined in the nanowires between the source and drain contacts on a Si/SiO2 substrate. We show that highly tunable QD devices can be realized with the MBE-grown InSb nanowires and the gate-to-dot capacitance extracted in the many-electron regimes is scaled linearly with the longitudinal dot size, demonstrating that the devices are of single InSb nanowire QDs even with a longitudinal size of similar to 700 nm. In the few-electron regime, the quantum levels in the QDs are resolved and the Lande g-factors extracted for the quantum levels from the magnetotransport measurements are found to be strongly level-dependent and fluctuated in a range of 18-48. A spin-orbit coupling strength is extracted from the magnetic field evolutions of a ground state and its neighboring excited state in an InSb nanowire QD and is on the order of similar to 300 mu eV. Our results establish that the MBE-grown InSb nanowires are of high crystal quality and are promising for the use in constructing novel quantum devices, such as entangled spin qubits, one-dimensional Wigner crystals and topological quantum computing devices.
|
|
| 9. |
- Fang, Li Tai, et al.
(author)
-
Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing
- 2021
-
In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1151-1160
-
Journal article (peer-reviewed)abstract
- Tumor-normal paired DNA samples from a breast cancer cell line and a matched lymphoblastoid cell line enable calibration of clinical sequencing pipelines and benchmarking 'tumor-only' or 'matched tumor-normal' analyses. The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor-normal genomic DNA (gDNA) samples derived from a breast cancer cell line-which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations-and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking 'tumor-only' or 'matched tumor-normal' analyses.
|
|
| 10. |
- Gottlieb, Bruce, et al.
(author)
-
Making Sense of Intratumor Genetic Heterogeneity : Altered Frequency of Androgen Receptor CAG Repeat Length Variants in Breast Cancer Tissues
- 2013
-
In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 34:4, s. 610-618
-
Journal article (peer-reviewed)abstract
- To examine the significance of intratumor genetic heterogeneity (ITGH) of the androgen receptor (AR) gene in breast cancer, patient-matched samples of laser capture microdissected breast tumor cells, adjacent normal breast epithelia cells, and peripheral blood leukocytes were sequenced using a novel next generation sequencing protocol. This protocol measured the frequency of distribution of a variable AR CAG repeat length, a functional polymorphism associated with breast cancer risk. All samples exhibited some degree of ITGH with up to 30 CAG repeat length variants identified. Each type of tissue exhibited a different distribution profile of CAG repeat lengths with substantial differences in the frequencies of zero and 1825 CAG AR variants. Tissue differences in the frequency of ARs with each of these CAG repeat lengths were significant as measured by paired, twin t-tests. These results suggest that preferential selection of 1825 CAG repeat length variants in breast tumors may be associated with breast cancer, and support the observation that shorter CAG repeats may protect against breast cancer. They also suggest that merely identifying variant genes will be insufficient to determine the critical mutational events of oncogenesis, which will require measuring the frequency of distribution of mutations within cancerous and matching normal tissues.
|
|
