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- Armstrong, Joel, et al.
(författare)
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Progressive Cactus is a multiple-genome aligner for the thousand-genome era
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7833, s. 246-251
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Tidskriftsartikel (refereegranskat)abstract
- New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies(1-3). For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database(4) increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019. In addition to this influx of assemblies from different species, new human de novo assemblies(5) are being produced, which enable the analysis of not only small polymorphisms, but also complex, large-scale structural differences between human individuals and haplotypes. This coming era and its unprecedented amount of data offer the opportunity to uncover many insights into genome evolution but also present challenges in how to adapt current analysis methods to meet the increased scale. Cactus(6), a reference-free multiple genome alignment program, has been shown to be highly accurate, but the existing implementation scales poorly with increasing numbers of genomes, and struggles in regions of highly duplicated sequences. Here we describe progressive extensions to Cactus to create Progressive Cactus, which enables the reference-free alignment of tens to thousands of large vertebrate genomes while maintaining high alignment quality. We describe results from an alignment of more than 600 amniote genomes, which is to our knowledge the largest multiple vertebrate genome alignment created so far. The Progressive Cactus program can create reference-free alignments of hundreds of large vertebrate genomes efficiently, and is used for the alignment of more than 600 amniote genomes.
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- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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- Han, Duo, et al.
(författare)
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Optimal Parameter Estimation Under Controlled Communication Over Sensor Networks
- 2015
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Ingår i: IEEE Transactions on Signal Processing. - : IEEE. - 1053-587X .- 1941-0476. ; 63:24, s. 6473-6485
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Tidskriftsartikel (refereegranskat)abstract
- This paper considers parameter estimation of linear systems under sensor-to-estimator communication constraint. Due to the limited battery power and the traffic congestion over a large sensor network, each sensor is required to reduce the rate of communication between the estimator and itself. We propose an observation-driven sensor scheduling policy such that the sensor transmits only the important measurements to the estimator. Unlike the existing deterministic scheduler, our stochastic scheduling is smartly designed to well compensate for the loss of the Gaussianity of the system. This results in a nice feature that the maximum-likelihood estimator (MLE) is still able to be recursively computed in a closed form, and the resulting estimation performance can be explicitly evaluated. Moreover, an optimization problem is formulated and solved to obtain the best parameters of the scheduling policy under which the estimation performance becomes comparable to the standard MLE with full measurements under a moderate transmission rate. Finally, simulations are included to validate the theoretical results.
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- Han, Duo, et al.
(författare)
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Stochastic Sensor Scheduling for Multiple Dynamical Processes over a Shared Channel
- 2016
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Ingår i: 2016 IEEE 55th Conference on Decision and Control, CDC 2016. - : IEEE. - 9781509018376 ; , s. 6315-6320
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Konferensbidrag (refereegranskat)abstract
- We consider the problem of multiple sensor scheduling for remote state estimation over a shared link. A number of sensors monitor different dynamical processes simultaneously but only one sensor can access the shared channel at each time instant to transmit the data packet to the estimator. We propose a stochastic event-based sensor scheduling framework in which each sensor makes transmission decisions based on both the channel accessibility and the self event-triggering condition. The corresponding optimal estimator is explicitly given. By ultilizing the realtime information, the proposed schedule is shown to be a generalization of the time based ones and outperform the time-based ones in terms of the estimation quality. By formulating an Markov decision process (MDP) problem with average cost criterion, we can find the optimal parameters for the event-based schedule. For practical use, we also design a simple suboptimal schedule to mitigate the computational complexity of solving an MDP problem. We also propose a method to quantify the optimality gap for any suboptimal schedules.
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- Xie, L, et al.
(författare)
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Off-tumor IDO1 target engagements determine the cancer-immune set point and predict the immunotherapeutic efficacy
- 2021
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Indoleamine-2,3-dioxygenase 1 (IDO1) has been intensively pursued as a therapeutic target to reverse the immunosuppressive cancer-immune milieu and promote tumor elimination. However, recent failures of phase III clinical trials with IDO1 inhibitors involved in cancer immunotherapies highlight the urgent need to develop appropriate methods for tracking IDO1 when the cancer-immune milieu is therapeutically modified.MethodsWe utilized a small-molecule radiotracer, 11C-l-1MTrp, to quantitatively and longitudinally visualize whole-body IDO1 dynamics. Specifically, we first assessed 11C-l-1MTrp in mice-bearing contralateral human tumors with distinct IDO1 expression patterns. Then, we applied 11C-l-1MTrp to longitudinally monitor whole-body IDO1 variations in immunocompetent melanoma-bearing mice treated with 1-methyl-l-tryptophan plus either chemotherapeutic drugs or antibodies targeting programmedcell death 1 and cytotoxic T-lymphocyte-associated protein 4.Results11C-l-1MTrp positron emission tomography (PET) imaging accurately delineated IDO1 expression in xenograft mouse models. Moreover, we were able to visualize dynamic IDO1 regulation in the mesenteric lymph nodes (MLNs), an off-tumor IDO1 target, where the percentage uptake of 11C-l-1MTrp accurately annotated the therapeutic efficacy of multiple combination immunotherapies in preclinical models. Remarkably, 11C-l-1MTrp signal intensity in the MLNs was inversely related to the specific growth rates of treated tumors, suggesting that IDO1 expression in the MLNs can serve as a new biomarker of the cancer-immune set point.ConclusionsPET imaging of IDO1 with 11C-l-1MTrp is a robust method to assess the therapeutic efficacy of multiple combinatorial immunotherapies, improving our understanding of the merit and challenges of IDO1 regimens. Further validation of this animal data in humans is ongoing. We envision that our results will provide a potential precision medicine paradigm for noninvasive visualizing each patient’s individual response in combinatorial cancer immunotherapy, and tailoring optimal personalized combination strategies.
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- Xie, ZJ, et al.
(författare)
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Light-induced tumor theranostics based on chemical-exfoliated borophene
- 2022
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Ingår i: Light, science & applications. - : Springer Science and Business Media LLC. - 2047-7538. ; 11:1, s. 324-
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Tidskriftsartikel (refereegranskat)abstract
- Among 2D materials (Xenes) which are at the forefront of research activities, borophene, is an exciting new entry due to its uniquely varied optical, electronic, and chemical properties in many polymorphic forms with widely varying band gaps including the lightest 2D metallic phase. In this paper, we used a simple selective chemical etching to prepare borophene with a strong near IR light-induced photothermal effect. The photothermal efficiency is similar to plasmonic Au nanoparticles, with the added benefit of borophene being degradable due to electron deficiency of boron. We introduce this selective chemical etching process to obtain ultrathin and large borophene nanosheets (thickness of ~4 nm and lateral size up to ~600 nm) from the precursor of AlB2. We also report first-time observation of a selective Acid etching behavior showing HCl etching of Al to form a residual B lattice, while HF selectively etches B to yield an Al lattice. We demonstrate that through surface modification with polydopamine (PDA), a biocompatible smart delivery nanoplatform of B@PDA can respond to a tumor environment, exhibiting an enhanced cellular uptake efficiency. We demonstrate that borophene can be more suitable for safe photothermal theranostic of thick tumor using deep penetrating near IR light compared to gold nanoparticles which are not degradable, thus posing long-term toxicity concerns. With about 40 kinds of borides, we hope that our work will open door to more discoveries of this top-down selective etching approach for generating borophene structures with rich unexplored thermal, electronic, and optical properties for many other technological applications.
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