Conductance of 1D quantum wires with anomalous electron-wavefunction localization

We study the statistics of the conductance $g$ through one-dimensional disordered systems where electron wavefunctions decay spatially as $|\psi| \sim \exp (-\lambda r^{\alpha})$ for $0 <\alpha <1$, $\lambda$ being a constant. In contrast to the conventional Anderson localization where $|\psi| \sim \exp (-\lambda r)$ and the conductance statistics is determined by a single parameter: the mean free path, here we show that when the wave function is anomalously localized ($\alpha <1$) the full statistics of the conductance is determined by the average $$ and the power $\alpha$. Our theoretical predictions are verified numerically by using a random hopping tight-binding model at zero energy, where due to the presence of chiral symmetry in the lattice there exists anomalous localization; this case corresponds to the particular value $\alpha =1/2$. To test our theory for other values of $\alpha$, we introduce a statistical model for the random hopping in the tight binding Hamiltonian.Comment: 6 pages, 8 figures. Few changes in the presentation and references updated. Published in PRB, Phys. Rev. B 85, 235450 (2012

Identification of single nucleotide variants using position-specific error estimation in deep sequencing data.

Background Targeted deep sequencing is a highly effective technology to identify known and novel single nucleotide variants (SNVs) with many applications in translational medicine, disease monitoring and cancer profiling. However, identification of SNVs using deep sequencing data is a challenging computational problem as different sequencing artifacts limit the analytical sensitivity of SNV detection, especially at low variant allele frequencies (VAFs).Methods To address the problem of relatively high noise levels in amplicon-based deep sequencing data (e.g. with the Ion AmpliSeq technology) in the context of SNV calling, we have developed a new bioinformatics tool called AmpliSolve. AmpliSolve uses a set of normal samples to model position-specific, strand-specific and nucleotide-specific background artifacts (noise), and deploys a Poisson model-based statistical framework for SNV detection.Results Our tests on both synthetic and real data indicate that AmpliSolve achieves a good trade-off between precision and sensitivity, even at VAF below 5% and as low as 1%. We further validate AmpliSolve by applying it to the detection of SNVs in 96 circulating tumor DNA samples at three clinically relevant genomic positions and compare the results to digital droplet PCR experiments.Conclusions AmpliSolve is a new tool for in-silico estimation of background noise and for detection of low frequency SNVs in targeted deep sequencing data. Although AmpliSolve has been specifically designed for and tested on amplicon-based libraries sequenced with the Ion Torrent platform it can, in principle, be applied to other sequencing platforms as well. AmpliSolve is freely available at https://github.com/dkleftogi/AmpliSolve

Identification of single nucleotide variants using position-specific error estimation in deep sequencing data

Background Targeted deep sequencing is a highly effective technology to identify known and novel single nucleotide variants (SNVs) with many applications in translational medicine, disease monitoring and cancer profiling. However, identification of SNVs using deep sequencing data is a challenging computational problem as different sequencing artifacts limit the analytical sensitivity of SNV detection, especially at low variant allele frequencies (VAFs). Methods To address the problem of relatively high noise levels in amplicon-based deep sequencing data (e.g. with the Ion AmpliSeq technology) in the context of SNV calling, we have developed a new bioinformatics tool called AmpliSolve. AmpliSolve uses a set of normal samples to model position-specific, strand-specific and nucleotide-specific background artifacts (noise), and deploys a Poisson model-based statistical framework for SNV detection. Results Our tests on both synthetic and real data indicate that AmpliSolve achieves a good trade-off between precision and sensitivity, even at VAF below 5% and as low as 1%. We further validate AmpliSolve by applying it to the detection of SNVs in 96 circulating tumor DNA samples at three clinically relevant genomic positions and compare the results to digital droplet PCR experiments. Conclusions AmpliSolve is a new tool for in-silico estimation of background noise and for detection of low frequency SNVs in targeted deep sequencing data. Although AmpliSolve has been specifically designed for and tested on amplicon-based libraries sequenced with the Ion Torrent platform it can, in principle, be applied to other sequencing platforms as well. AmpliSolve is freely available at https://github.com/dkleftogi/AmpliSolve

Identification of single nucleotide variants using position-specific error estimation in deep sequencing data

BACKGROUND: Targeted deep sequencing is a highly effective technology to identify known and novel single nucleotide variants (SNVs) with many applications in translational medicine, disease monitoring and cancer profiling. However, identification of SNVs using deep sequencing data is a challenging computational problem as different sequencing artifacts limit the analytical sensitivity of SNV detection, especially at low variant allele frequencies (VAFs). METHODS: To address the problem of relatively high noise levels in amplicon-based deep sequencing data (e.g. with the Ion AmpliSeq technology) in the context of SNV calling, we have developed a new bioinformatics tool called AmpliSolve. AmpliSolve uses a set of normal samples to model position-specific, strand-specific and nucleotide-specific background artifacts (noise), and deploys a Poisson model-based statistical framework for SNV detection. RESULTS: Our tests on both synthetic and real data indicate that AmpliSolve achieves a good trade-off between precision and sensitivity, even at VAF below 5% and as low as 1%. We further validate AmpliSolve by applying it to the detection of SNVs in 96 circulating tumor DNA samples at three clinically relevant genomic positions and compare the results to digital droplet PCR experiments. CONCLUSIONS: AmpliSolve is a new tool for in-silico estimation of background noise and for detection of low frequency SNVs in targeted deep sequencing data. Although AmpliSolve has been specifically designed for and tested on amplicon-based libraries sequenced with the Ion Torrent platform it can, in principle, be applied to other sequencing platforms as well. AmpliSolve is freely available at https://github.com/dkleftogi/AmpliSolve

Ultra-Sensitive Mutation Detection and Genome-Wide DNA Copy Number Reconstruction by Error-Corrected Circulating Tumor DNA Sequencing.

Background Circulating free DNA sequencing (cfDNA-Seq) can portray cancer genome landscapes, but highly sensitive and specific technologies are necessary to accurately detect mutations with often low variant frequencies.Methods We developed a customizable hybrid-capture cfDNA-Seq technology using off-the-shelf molecular barcodes and a novel duplex DNA molecule identification tool for enhanced error correction.Results Modeling based on cfDNA yields from 58 patients showed that this technology, requiring 25 ng of cfDNA, could be applied to >95% of patients with metastatic colorectal cancer (mCRC). cfDNA-Seq of a 32-gene, 163.3-kbp target region detected 100% of single-nucleotide variants, with 0.15% variant frequency in spike-in experiments. Molecular barcode error correction reduced false-positive mutation calls by 97.5%. In 28 consecutively analyzed patients with mCRC, 80 out of 91 mutations previously detected by tumor tissue sequencing were called in the cfDNA. Call rates were similar for point mutations and indels. cfDNA-Seq identified typical mCRC driver mutations in patients in whom biopsy sequencing had failed or did not include key mCRC driver genes. Mutations only called in cfDNA but undetectable in matched biopsies included a subclonal resistance driver mutation to anti-EGFR antibodies in KRAS , parallel evolution of multiple PIK3CA mutations in 2 cases, and TP53 mutations originating from clonal hematopoiesis. Furthermore, cfDNA-Seq off-target read analysis allowed simultaneous genome-wide copy number profile reconstruction in 20 of 28 cases. Copy number profiles were validated by low-coverage whole-genome sequencing.Conclusions This error-corrected, ultradeep cfDNA-Seq technology with a customizable target region and publicly available bioinformatics tools enables broad insights into cancer genomes and evolution.Clinicaltrialsgov identifier NCT02112357

Development, application and evaluation of a 1-D full life cycle anchovy and sardine model for the North Aegean Sea (Eastern Mediterranean)

A 1-D full-life-cycle, Individual-based model (IBM), two-way coupled with a hydrodynamic/ biogeochemical model, is demonstrated for anchovy and sardine in the N. Aegean Sea (Eastern Mediterranean). The model is stage-specific and includes a ‘Wisconsin’ type bioenergetics, a diel vertical migration and a population dynamics module, with the incorporation of known differences in biological attributes between the anchovy and sardine stocks. A new energy allocation/egg production algorithm was developed, allowing for breeding pattern to move along the capital-income breeding continuum. Fish growth was calibrated against available size-at-age data by tuning food consumption (the half saturation coefficients) using a genetic algorithm. After a ten-years spin up, the model reproduced well the magnitude of population biomasses and spawning periods of the two species in the N. Aegean Sea. Surprisingly, model simulations revealed that anchovy depends primarily on stored energy for egg production (mostly capital breeder) whereas sardine depends heavily on direct food intake (income breeder). This is related to the peculiar phenology of plankton production in the area, with mesozooplankton concentration exhibiting a sharp decrease from early summer to autumn and a subsequent increase from winter to early summer. Monthly changes in somatic condition of fish collected on board the commercial purse seine fleet followed closely the simulated mesozooplankton concentration. Finally, model simulations showed that, when both the anchovy and sardine stocks are overexploited, the mesozooplankton concentration increases, which may open up ecological space for competing species. The importance of protecting the recruit spawners was highlighted with model simulations testing the effect of changing the timing of the existing 2.5-months closed period. Optimum timing for fishery closure is different for anchovy and sardine because of their opposite spawning and recruitment periods. © 2019 Gkanasos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited