Suppressing Grating Lobes for Transcranial Focused Ultrasound System by Frequency-Modulated Excitation.

Transcranial focused ultrasound is a novel noninvasive therapeutic modality for glioblastoma and other disorders of the brain. However, because the phase aberrations caused by the skull need to be corrected with computed tomography (CT) images, the transcranial transducer is tightly fixed on the patient's head to avoid any variation in the relative position, and the focus shifting relies mainly on the capacity for electronic beam steering. Due to the presence of grating lobes and the rapid degradation of the focus quality with increasing focus-shifting distance, transcranial focus-shifting sonication may damage healthy brain tissue unintentionally. To reduce the risks associated with transcranial focused ultrasound therapy, linear frequency-modulated (FM) excitation is proposed. The k-space corrected pseudospectral time domain (PSTD) and acoustic holography approach based on the Rayleigh integral are combined to calculate the distribution of the deposited acoustic power. The corresponding simulation was performed with axial/lateral focus shifting at different distances. The distributions of the deposited acoustic power show that linear FM excitation can effectively suppress undesired prefocal grating lobes without compromising focus quality.

Design of a Versatile Angle-Rotatable Skull-Shaped Conformal Transcranial Focused Ultrasound Transducer for Noninvasive Brain Therapy.

Phase-controlled focused ultrasound transducers have opened up a new way to noninvasively treat brain diseases. However, due to the geometry and the heterogeneous medium of the human skull, the currently used hemispherical transducers cannot guarantee that the ultrasound emitted by the transducer penetrates the skull normally; consequently, the impact of the shear wave on the treatment area has to be considered. The usual approach is to turn off elements in the transducer with excessively large incident angles, but this approach reduces the efficiency of the transducer. This article presents the design of a novel transducer that can be rotated according to the different geometric shapes of the skull. The incident angles of the elements in the transducer are modified so that the effect of the shear wave on the treatment area can be ignored and the efficiency of the transducer is improved. The results of computed tomography (CT) model simulation of nine skulls verify the versatility and feasibility of the new transducer. We believe that this kind of rotatable transducer has clinical and engineering significance.

An efficient and accurate parallel hybrid acoustic signal correction method for transcranial ultrasound.

Phased-control focused ultrasound transducers provide a new and noninvasive treatment method for brain disease. However, improving the accuracy of phase correction and reducing the calculation time during treatment have always been contradictory constraints. In this paper, a hybrid acoustic signal correction (HASC) method combined with k-Wave stage and holography stage was introduced for phase correction and simulation of transcranial focused ultrasound. The k-Wave stage is mainly used to calculate the sound field in a heterogeneous medium (skull), which divides the sound field calculation process into paths that can be calculated in parallel, and the transcranial correction phase can also be obtained during the calculation. The holography stage is sufficient to simulate the acoustic field in the homogenous intracranial medium after ultrasound transmitting through the skull. The agreement of the k-space corrected pseudospectral time domain method and HASC method was assessed by statistical methods: linear regression between the two methods provided a slope of 0.9735, intercept of 0.0078, and R 2 of 0.9982. The Bland-Altman method provided a bias of 0.0015 and 95% limits of agreement 0.065 apart. We demonstrated that the difference in sound intensity at the focal point corrected by HASC and time reversal phase correction method was 0.2% and 0.5% in the results of simulation and experiment, respectively. Not only that, the phase calculation time by the HASC phase correction method can be reduced to 11 min on a multi GPU array, which has clinical potential for ultrasound treatment of brain therapy.

Significant variations in alternative splicing patterns and expression profiles between human-mouse orthologs in early embryos.

Human and mouse orthologs are expected to have similar biological functions; however, many discrepancies have also been reported. We systematically compared human and mouse orthologs in terms of alternative splicing patterns and expression profiles. Human-mouse orthologs are divergent in alternative splicing, as human orthologs could generally encode more isoforms than their mouse orthologs. In early embryos, exon skipping is far more common with human orthologs, whereas constitutive exons are more prevalent with mouse orthologs. This may correlate with divergence in expression of splicing regulators. Orthologous expression similarities are different in distinct embryonic stages, with the highest in morula. Expression differences for orthologous transcription factor genes could play an important role in orthologous expression discordance. We further detected largely orthologous divergence in differential expression between distinct embryonic stages. Collectively, our study uncovers significant orthologous divergence from multiple aspects, which may result in functional differences and dynamics between human-mouse orthologs during embryonic development.

PhaseTank: genome-wide computational identification of phasiRNAs and their regulatory cascades.

UNLABELLED: Emerging evidence has revealed phased siRNAs (phasiRNAs) as important endogenous regulators in plants. However, the integrated prediction tools for phasiRNAs are still limited. In this article, we introduce a stand-alone package PhaseTank for systematically characterizing phasiRNAs and their regulatory networks. (i) It can identify phasiRNAs/tasiRNAs functional cascades (miRNA/phasiRNA → PHAS loci → phasiRNA → target) with high sensitivity and specificity. (ii) By one command analysis, it generates comprehensive annotation and quantification of the predicted PHAS genes from any given sequences. (iii) PhaseTank has no restriction with regards to prior information of sequence homology of unrestricted organism origins. AVAILABILITY AND IMPLEMENTATION: PhaseTank is a free and open-source tool. The package is available at http://phasetank.sourceforge.net/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comprehensively identifying and characterizing the missing gene sequences in human reference genome with integrated analytic approaches.

The human reference genome is still incomplete and a number of gene sequences are missing from it. The approaches to uncover them, the reasons causing their absence and their functions are less explored. Here, we comprehensively identified and characterized the missing genes of human reference genome with RNA-Seq data from 16 different human tissues. By using a combined approach of genome-guided transcriptome reconstruction coupled with genome-wide comparison, we uncovered 3.78 and 2.37 Mb transcribed regions in the human genome assemblies of Celera and HuRef either missed from their homologous chromosomes of NCBI human reference genome build 37.2 or partially or entirely absent from the reference. We further identified a significant number of novel transcript contigs in each tissue from de novo transcriptome assembly that are unalignable to NCBI build 37.2 but can be aligned to at least one of the genomes from Celera, HuRef, chimpanzee, macaca or mouse. Our analyses indicate that the missing genes could result from genome misassembly, transposition, copy number variation, translocation and other structural variations. Moreover, our results further suggest that a large portion of these missing genes are conserved between human and other mammals, implying their important biological functions. Totally, 1,233 functional protein domains were detected in these missing genes. Collectively, our study not only provides approaches for uncovering the missing genes of a genome, but also proposes the potential reasons causing genes missed from the genome and highlights the importance of uncovering the missing genes of incomplete genomes.

Incorporating the human gene annotations in different databases significantly improved transcriptomic and genetic analyses.

Human gene annotation is crucial for conducting transcriptomic and genetic studies; however, the impacts of human gene annotations in diverse databases on related studies have been less evaluated. To enable full use of various human annotation resources and better understand the human transcriptome, here we systematically compare the human annotations present in RefSeq, Ensembl (GENCODE), and AceView on diverse transcriptomic and genetic analyses. We found that the human gene annotations in the three databases are far from complete. Although Ensembl and AceView annotated more genes than RefSeq, more than 15,800 genes from Ensembl (or AceView) are within the intergenic and intronic regions of AceView (or Ensembl) annotation. The human transcriptome annotations in RefSeq, Ensembl, and AceView had distinct effects on short-read mapping, gene and isoform expression profiling, and differential expression calling. Furthermore, our findings indicate that the integrated annotation of these databases can obtain a more complete gene set and significantly enhance those transcriptomic analyses. We also observed that many more known SNPs were located within genes annotated in Ensembl and AceView than in RefSeq. In particular, 1033 of 3041 trait/disease-associated SNPs involved in about 200 human traits/diseases that were previously reported to be in RefSeq intergenic regions could be relocated within Ensembl and AceView genes. Our findings illustrate that a more complete transcriptome generated by incorporating human gene annotations in diverse databases can strikingly improve the overall results of transcriptomic and genetic studies.