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2.
Cochlear Implants Int ; : 1-6, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38353257

ABSTRACT

OBJECTIVES: Children with cochlear nerve deficiency (CND) have wide variability in outcomes with cochlear implant (CI) use. The current study aims to report a large cohort of pediatric CI recipients with CND and to evaluate for factors that may predict improved performance. METHODS: The current study is a retrospective review of pediatric CI recipients with CND at a tertiary academic hospital. Variables including cochlear nerve status (hypoplasia vs aplasia), age at implantation, cochleovestibular malformation, bony cochlear nerve aperture, internal auditory canal aperture, and cognitive delay were evaluated for predictors of postoperative performance. A stepwise multinomial regression analysis was performed. RESULTS: Forty-seven CI recipients (54 ears) were included in the analysis. A majority (59%) showed auditory capabilities with their CI. Twenty percent of recipients achieved some level of open-set speech perception with their CI. The regression analysis identified cochlear nerve status and cognitive delay as predictors of performance. CI recipients with cochlear nerve hypoplasia had significantly improved performance compared to those with aplasia (p = 0.003). Recipients with cognitive delay had more limited benefit than those without cognitive delay (p = 0.033). CONCLUSIONS: Children with CND can benefit from CI use, with outcomes spanning from non-use to development of spoken language. Predictive factors for improved performance include a lack of cognitive delay and cochlear hypoplasia rather than aplasia. These can be important considerations for parent counseling and decision making.

3.
Cell Rep Methods ; 3(11): 100625, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37918402

ABSTRACT

Single-cell whole-genome sequencing (scWGS) enables the assessment of genome-level molecular differences between individual cells with particular relevance to genetically diverse systems like solid tumors. The application of scWGS was limited due to a dearth of accessible platforms capable of producing high-throughput profiles. We present a technique that leverages nucleosome disruption methodologies with the widely adopted 10× Genomics ATAC-seq workflow to produce scWGS profiles for high-throughput copy-number analysis without new equipment or custom reagents. We further demonstrate the use of commercially available indexed transposase complexes from ScaleBio for sample multiplexing, reducing the per-sample preparation costs. Finally, we demonstrate that sequential indexed tagmentation with an intervening nucleosome disruption step allows for the generation of both ATAC and WGS data from the same cell, producing comparable data to the unimodal assays. By exclusively utilizing accessible commercial reagents, we anticipate that these scWGS and scWGS+ATAC methods can be broadly adopted by the research community.


Subject(s)
Chromatin , Nucleosomes , Chromatin/genetics , Nucleosomes/genetics , Sequence Analysis, DNA/methods , High-Throughput Nucleotide Sequencing/methods , Genome
4.
Audiol Neurootol ; 28(6): 478-487, 2023.
Article in English | MEDLINE | ID: mdl-37482054

ABSTRACT

INTRODUCTION: Cochlear implant (CI) and electric-acoustic stimulation (EAS) users may experience better performance with maps that align the electric filter frequencies to the cochlear place frequencies, known as place-based maps, than with maps that present spectrally shifted information. Individual place-based mapping procedures differ in the frequency content that is aligned to cochlear tonotopicity versus discarded or spectrally shifted. The performance benefit with different place-based maps may vary due to individual differences in angular insertion depth (AID) of the electrode array and whether functional acoustic low-frequency information is available in the implanted ear. The present study compared masked speech recognition with two types of place-based maps as a function of AID and presence of acoustic low-frequency information. METHODS: Sixty adults with normal hearing listened acutely to CI or EAS simulations of two types of place-based maps for one of three cases of electrode arrays at shallow AIDs. The strict place-based (Strict-PB) map aligned the low- and mid-frequency information to cochlear tonotopicity and discarded information below the frequency associated with the most apical electrode contact. The alternative place-based map (LFshift-PB) aligned the mid-frequency information to cochlear tonotopicity and provided more of the speech spectrum by compressing low-frequency information on the apical electrode contacts (i.e., <1 kHz). Three actual cases of a 12-channel, 24-mm electrode array were simulated by assigning the carrier frequency for an individual channel as the cochlear place frequency of the associated electrode contact. The AID and cochlear place frequency for the most apical electrode contact were 460° and 498 Hz for case 1, 389° and 728 Hz for case 2, and 335° and 987 Hz for case 3, respectively. RESULTS: Generally, better performance was observed with the Strict-PB maps for cases 1 and 2, where mismatches were 2-4 octaves for the most apical channel with the LFshift-PB map. Similar performance was observed between maps for case 3. For the CI simulations, performance with the Strict-PB map declined with decreases in AID, while performance with the LFshift-PB map remained stable across cases. For the EAS simulations, performance with the Strict-PB map remained stable across cases, while performance with the LFshift-PB map improved with decreases in AID. CONCLUSIONS: Listeners demonstrated differences with the Strict-PB versus LFshift-PB maps as a function of AID and whether acoustic low-frequency information was available (CI vs. EAS). These data support the use of the Strict-PB mapping procedure for AIDs ≥335°, though further study including time for acclimatization in CI and EAS users is warranted.


Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Adult , Humans , Cochlear Implantation/methods , Cochlea , Acoustic Stimulation , Speech Perception/physiology , Acoustics , Electric Stimulation
5.
bioRxiv ; 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37502923

ABSTRACT

DNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap). Sufficient off-target coverage further enables the production of near-complete methylomes for individual cell types. We characterize sciMET-cap on human PBMCs and brain (middle frontal gyrus).

6.
Genome Res ; 33(2): 208-217, 2023 02.
Article in English | MEDLINE | ID: mdl-36792372

ABSTRACT

Here we present advancements in single-cell combinatorial indexed Assay for Transposase Accessible Chromatin (sciATAC) to measure chromatin accessibility that leverage nanowell chips to achieve atlas-scale cell throughput (>105 cells) at low cost. The platform leverages the core of the sciATAC workflow where multiple indexed tagmentation reactions are performed, followed by pooling and distribution to a second set of reaction wells for polymerase chain reaction (PCR)-based indexing. In this work, we instead leverage a chip containing 5184 nanowells at the PCR stage of indexing, enabling a 52-fold improvement in scale and reduction in per-cell preparation costs. We detail three variants that balance cell throughput and depth of coverage, and apply these methods to banked mouse brain tissue, producing maps of cell types as well as neuronal subtypes that include integration with existing single-cell Assay for Transposase Accessible Chromatin (scATAC) and scRNA-seq data sets. Our optimized workflow achieves a high fraction of reads that fall within called peaks (>80%) and low cell doublet rates. The high cell coverage technique produces high unique reads per cell, while retaining high enrichment for open chromatin regions, enabling the assessment of >70,000 unique accessible loci on average for each cell profiled. When compared to current methods in the field, our technique provides similar or superior per-cell information with very low levels of cell-to-cell cross talk, and achieves this at a cost point much lower than existing assays.


Subject(s)
Chromatin , Transposases , Mice , Animals , Transposases/metabolism , Neurons/metabolism , Epigenomics/methods , Single-Cell Analysis/methods
7.
Am J Audiol ; 32(1): 251-260, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36800505

ABSTRACT

PURPOSE: Cochlear implant (CI) recipients with hearing preservation experience significant improvements in speech recognition with electric-acoustic stimulation (EAS) as compared to with a CI alone, although outcomes across EAS users vary. The individual differences in performance may be due in part to default mapping procedures, which result in electric frequency-to-place mismatches for the majority of EAS users. This study assessed the influence of electric mismatches on the early speech recognition for EAS users. METHOD: Twenty-one participants were randomized at EAS activation to listen exclusively with a default or place-based map. For both groups, the unaided thresholds determined the acoustic cutoff frequency (i.e., > 65 dB HL). For default maps, the electric filter frequencies were assigned to avoid spectral gaps in frequency information but created varying magnitudes of mismatches. For place-based maps, the electric filter frequencies were assigned to avoid frequency-to-place mismatches. Recognition of consonant-nucleus-consonant words and vowels was assessed at activation and 1, 3, and 6 months postactivation. RESULTS: For participants with default maps, electric mismatch at 1500 Hz ranged from 2 to -12.0 semitones (Mdn = -5 semitones). Poorer performance was observed for those with larger magnitudes of electric mismatch. This effect was observed through 6 months of EAS listening experience. CONCLUSIONS: The present sample of EAS users experienced better initial performance when electric mismatches were small or eliminated. These data suggest the utility of methods that reduce electric mismatches, such as place-based mapping procedures. Investigation is ongoing to determine whether these differences persist with long-term EAS use. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22096523.


Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Humans , Acoustic Stimulation/methods , Speech Perception/physiology , Cochlear Implantation/methods , Hearing
8.
Cell ; 186(2): 305-326.e27, 2023 01 19.
Article in English | MEDLINE | ID: mdl-36638792

ABSTRACT

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation. These data are consistent with the information theory of aging, which states that a loss of epigenetic information is a reversible cause of aging.


Subject(s)
Aging , Epigenesis, Genetic , Animals , Aging/genetics , DNA Methylation , Epigenome , Mammals/genetics , Nucleoproteins , Saccharomyces cerevisiae/genetics
9.
Nat Commun ; 13(1): 7627, 2022 Dec 09.
Article in English | MEDLINE | ID: mdl-36494343

ABSTRACT

DNA methylation is a key epigenetic property that drives gene regulatory programs in development and disease. Current single-cell methods that produce high quality methylomes are expensive and low throughput without the aid of extensive automation. We previously described a proof-of-principle technique that enabled high cell throughput; however, it produced only low-coverage profiles and was a difficult protocol that required custom sequencing primers and recipes and frequently produced libraries with excessive adapter contamination. Here, we describe a greatly improved version that generates high-coverage profiles (~15-fold increase) using a robust protocol that does not require custom sequencing capabilities, includes multiple stopping points, and exhibits minimal adapter contamination. We demonstrate two versions of sciMETv2 on primary human cortex, a high coverage and rapid version, identifying distinct cell types using CH methylation patterns. These datasets are able to be directly integrated with one another as well as with existing snmC-seq2 datasets with little discernible bias. Finally, we demonstrate the ability to determine cell types using CG methylation alone, which is the dominant context for DNA methylation in most cell types other than neurons and the most applicable analysis outside of brain tissue.


Subject(s)
DNA Methylation , High-Throughput Nucleotide Sequencing , Humans , DNA Methylation/genetics , Sequence Analysis, DNA , Epigenomics/methods , Software
10.
CRISPR J ; 5(4): 548-557, 2022 08.
Article in English | MEDLINE | ID: mdl-35833801

ABSTRACT

Targeted sequencing remains a valuable technique for clinical and research applications. However, many existing technologies suffer from pervasive guanine-cytosine (GC) sequence content bias, high input DNA requirements, and high cost for custom panels. We have developed Cas12a-Capture, a low-cost and highly scalable method for targeted sequencing. The method utilizes preprogrammed guide RNAs to direct CRISPR-Cas12a cleavage of double-stranded DNA in vitro and then takes advantage of the resulting four to five nucleotide overhangs for selective ligation with a custom sequencing adapter. Addition of a second sequencing adapter and enrichment for ligation products generates a targeted sequence library. We first performed a pilot experiment with 7176 guides targeting 3.5 Mb of DNA. Using these data, we modeled the sequence determinants of Cas12a-Capture efficiency, then designed an optimized set of 11,438 guides targeting 3.0 Mb. The optimized guide set achieves an average 64-fold enrichment of targeted regions with minimal GC bias. Cas12a-Capture variant calls had strong concordance with Illumina Platinum Genome calls, especially for single nucleotide variants, which could be improved by applying basic variant quality heuristics. We believe Cas12a-Capture has a wide variety of potential clinical and research applications and is amendable for selective enrichment for any double-stranded DNA template or genome.


Subject(s)
CRISPR-Cas Systems , Gene Editing , CRISPR-Cas Systems/genetics , DNA/genetics , Gene Editing/methods , Nucleotides , RNA, Guide, Kinetoplastida/genetics
11.
Am J Audiol ; 31(2): 322-337, 2022 Jun 02.
Article in English | MEDLINE | ID: mdl-35394798

ABSTRACT

PURPOSE: Cochlear implant (CI) recipients demonstrate variable speech recognition when listening with a CI-alone or electric-acoustic stimulation (EAS) device, which may be due in part to electric frequency-to-place mismatches created by the default mapping procedures. Performance may be improved if the filter frequencies are aligned with the cochlear place frequencies, known as place-based mapping. Performance with default maps versus an experimental place-based map was compared for participants with normal hearing when listening to CI-alone or EAS simulations to observe potential outcomes prior to initiating an investigation with CI recipients. METHOD: A noise vocoder simulated CI-alone and EAS devices, mapped with default or place-based procedures. The simulations were based on an actual 24-mm electrode array recipient, whose insertion angles for each electrode contact were used to estimate the respective cochlear place frequency. The default maps used the filter frequencies assigned by the clinical software. The filter frequencies for the place-based maps aligned with the cochlear place frequencies for individual contacts in the low- to mid-frequency cochlear region. For the EAS simulations, low-frequency acoustic information was filtered to simulate aided low-frequency audibility. Performance was evaluated for the AzBio sentences presented in a 10-talker masker at +5 dB signal-to-noise ratio (SNR), +10 dB SNR, and asymptote. RESULTS: Performance was better with the place-based maps as compared with the default maps for both CI-alone and EAS simulations. For instance, median performance at +10 dB SNR for the CI-alone simulation was 57% correct for the place-based map and 20% for the default map. For the EAS simulation, those values were 59% and 37% correct. Adding acoustic low-frequency information resulted in a similar benefit for both maps. CONCLUSIONS: Reducing frequency-to-place mismatches, such as with the experimental place-based mapping procedure, produces a greater benefit in speech recognition than maximizing bandwidth for CI-alone and EAS simulations. Ongoing work is evaluating the initial and long-term performance benefits in CI-alone and EAS users. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19529053.


Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Acoustic Stimulation , Acoustics , Humans
12.
Sci Adv ; 8(5): eabi5884, 2022 Feb 04.
Article in English | MEDLINE | ID: mdl-35108053

ABSTRACT

Animal genomes show networks of deeply conserved gene linkages whose phylogenetic scope and chromosomal context remain unclear. Here, we report chromosome-scale conservation of synteny among bilaterians, cnidarians, and sponges and use comparative analysis to reconstruct ancestral chromosomes across major animal groups. Comparisons among diverse metazoans reveal the processes of chromosome evolution that produced contemporary karyotypes from their Precambrian progenitors. On the basis of these findings, we introduce a simple algebraic representation of chromosomal change and use it to establish a unified systematic framework for metazoan chromosome evolution. We find that fusion-with-mixing, a previously unappreciated mode of chromosome change, has played a central role. We find that relicts of several metazoan chromosomal units are preserved in unicellular eukaryotes. These conserved pre-metazoan linkages include the chromosomal unit that encodes the most diverse set of metazoan homeobox genes, suggesting a candidate genomic context for the early diversification of this key gene family.

13.
Otol Neurotol ; 43(2): 183-189, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34772886

ABSTRACT

OBJECTIVES: 1) To compare speech recognition outcomes between cochlear implant (CI) recipients of 28- and 31.5-mm lateral wall electrode arrays, and 2) to characterize the relationship between angular insertion depth (AID) and speech recognition. STUDY DESIGN: Retrospective review. SETTING: Tertiary academic referral center. PATIENTS: Seventy-five adult CI recipients of fully inserted 28-mm (n = 28) or 31.5-mm (n = 47) lateral wall arrays listening with a CI-alone device. INTERVENTIONS: Cochlear implantation with postoperative computed tomography. MAIN OUTCOME MEASURES: Consonant-nucleus-consonant (CNC) word recognition assessed with the CI-alone at 12 months postactivation. RESULTS: The mean AID of the most apical electrode contact for the 31.5-mm array recipients was significantly deeper than the 28-mm array recipients (628° vs 571°, p < 0.001). Following 12 months of listening experience, mean CNC word scores were significantly better for recipients of 31.5-mm arrays compared with those implanted with 28-mm arrays (59.5% vs 48.3%, p = 0.004; Cohen's d = 0.70; 95% CI [0.22, 1.18]). There was a significant positive correlation between AID and CNC word scores (r = 0.372, p = 0.001), with a plateau in performance observed around 600°. CONCLUSIONS: Cochlear implant recipients implanted with a 31.5-mm array experienced better speech recognition than those with a 28-mm array at 12 months postactivation. Deeper insertion of a lateral wall array appears to confer speech recognition benefit up to ∼600°, with a plateau in performance observed thereafter. These data provide preliminary evidence of the insertion depth necessary to optimize speech recognition outcomes for lateral wall electrode arrays among CI-alone users.


Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Adult , Cochlear Implantation/methods , Cochlear Implants/adverse effects , Humans , Retrospective Studies , Speech , Speech Perception/physiology
14.
Otol Neurotol ; 43(1): e72-e78, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34739427

ABSTRACT

OBJECTIVES: To compare intraoperative intracochlear electrocochleography (ECochG) with hearing preservation outcomes in cochlear implant (CI) subjects. DESIGN: Intraoperative electrocochleography was performed in adult CI subjects who were recipients of Advanced Bionics' Bionics LLC precurved HiFocus MidScala or straight HiFocus SlimJ electrode arrays. ECochG responses were recorded from the most apical electrode contact during insertion. No changes to the insertions were made due to ECochG monitoring. No information about insertion resistance was collected. ECochG drops were estimated as the change in amplitude from peak (defined as maximum amplitude response) to drop (largest drop) point after the peak during insertion was measured following the peak response. Audiometric thresholds from each subject were obtained before and approximately 1 month after CI surgery. The change in pure tone average for frequencies between 125 Hz and 500 Hz was measured after surgery. No postoperative CT scans were collected as part of this study. RESULTS: A total of 68 subjects from five surgical centers participated in the study. The study sample included 30 MidScala and 38 SlimJ electrodes implanted by approximately 20 surgeons who contributed to the study. Although a wide range of results were observed, there was a moderate positive correlation (Pearson Correlation coefficient, r = 0.56, p < 0.01) between the size of the ECochG drop and the magnitude of pure tone average change. This trend was present for both the MidScala and SlimJ arrays. The SlimJ and MidScala arrays produced significantly different hearing loss after surgery. CONCLUSION: Large ECochG amplitude drops observed during electrode insertion indicated poorer hearing preservation. Although the outcomes were variable, this information may be helpful to guide surgical decision-making when contemplating full electrode insertion and the likelihood of hearing preservation.


Subject(s)
Cochlear Implantation , Cochlear Implants , Adult , Audiometry, Evoked Response/methods , Cochlea/diagnostic imaging , Cochlea/surgery , Cochlear Implantation/methods , Hearing , Humans
15.
Audiol Neurootol ; 27(3): 227-234, 2022.
Article in English | MEDLINE | ID: mdl-34808626

ABSTRACT

INTRODUCTION: The objective of this study was to assess the influence of postponing the first post-activation follow-up due to the COVID-19 pandemic on the aided sound field detection thresholds and speech recognition of cochlear implant (CI) users. METHODS: A retrospective review was performed at a tertiary referral center. Two groups of adult CI recipients were evaluated: (1) patients whose first post-activation follow-up was postponed due to COVID-19 closures (postponed group; n = 10) and (2) a control group that attended recommended post-activation follow-ups prior to the COVID-19 pandemic (control group; n = 18). For both groups, electric thresholds were estimated at initial activation based on comfort levels and were measured behaviorally at subsequent post-activation follow-ups. For the control group, behavioral thresholds were measured at the 1-month follow-up. For the postponed group, behavioral thresholds were not measured until 3 months post-activation since the 1-month follow-up was postponed. The aided pure-tone average (PTA) and word recognition results were compared between groups at the 3-month follow-up and at an interim visit 2-9 weeks later. RESULTS: At the 3-month follow-up, the postponed group had significantly poorer word recognition (23 vs. 42%, p = 0.027) and aided PTA (42 vs. 37 dB HL, p = 0.041) than the control group. No significant differences were observed between 3-month data from the control group and interim data from the postponed group. CONCLUSIONS: The postponed follow-up after CI activation was associated with poorer outcomes, both in terms of speech recognition and aided audibility. However, these detrimental effects were reversed following provision of an individualized map, with behaviorally measured electric threshold and comfort levels. While adult CI recipients demonstrate an improvement in speech recognition with estimated electric thresholds, the present results suggest that behavioral mapping within the initial weeks of device use may support optimal outcomes.


Subject(s)
COVID-19 , Cochlear Implantation , Cochlear Implants , Speech Perception , Adult , Auditory Threshold , Cochlear Implantation/methods , Follow-Up Studies , Humans , Pandemics , Speech Perception/physiology
16.
Otol Neurotol ; 42(9): e1234-e1241, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34224547

ABSTRACT

OBJECTIVE: Assess the influence of cochlear implant (CI) use on the perceived listening effort of adult and pediatric subjects with unilateral hearing loss (UHL) or asymmetric hearing loss (AHL). STUDY DESIGN: Prospective cohort. SETTING: Tertiary referral center. PATIENTS: Adults and children with UHL or AHL. INTERVENTION: Cochlear implantation. Subjects received their CI as part of a clinical trial assessing the effectiveness of cochlear implantation in cases of UHL and AHL. MAIN OUTCOME MEASURES: Responses to the Listening Effort pragmatic subscale on the Speech, Spatial, and Qualities of Hearing Scale (SSQ) or SSQ for Children with Impaired Hearing (SSQ-C) were compared over the study period. Subjects or their parents completed the questionnaires preoperatively and at predetermined postactivation intervals. For the adult subjects, responses were compared to word recognition in quiet and sentence recognition in noise. RESULTS: Forty adult subjects (n = 20 UHL, n = 20 AHL) and 16 pediatric subjects with UHL enrolled and underwent cochlear implantation. Subjects in all three groups reported a significant reduction in perceived listening effort within the initial months of CI use (p < 0.001; η2 ≥ 0.351). The perceived benefit was significantly correlated with speech recognition in noise for the adult subjects with UHL at the 12-month interval (r(20) = .59, p = 0.006). CONCLUSIONS: Adult and pediatric CI recipients with UHL or AHL report a reduction in listening effort with CI use as compared to their preoperative experiences. Use of the SSQ and SSQ-C Listening Effort pragmatic subscale may provide additional information about a CI recipient's experience beyond the abilities measured in the sound booth.


Subject(s)
Cochlear Implantation , Cochlear Implants , Hearing Loss, Unilateral , Hearing Loss , Speech Perception , Adult , Child , Hearing Loss, Unilateral/surgery , Humans , Prospective Studies , Treatment Outcome
17.
Nat Biotechnol ; 39(12): 1574-1580, 2021 12.
Article in English | MEDLINE | ID: mdl-34226710

ABSTRACT

Single-cell combinatorial indexing (sci) with transposase-based library construction increases the throughput of single-cell genomics assays but produces sparse coverage in terms of usable reads per cell. We develop symmetrical strand sci ('s3'), a uracil-based adapter switching approach that improves the rate of conversion of source DNA into viable sequencing library fragments following tagmentation. We apply this chemistry to assay chromatin accessibility (s3-assay for transposase-accessible chromatin, s3-ATAC) in human cortical and mouse whole-brain tissues, with mouse datasets demonstrating a six- to 13-fold improvement in usable reads per cell compared with other available methods. Application of s3 to single-cell whole-genome sequencing (s3-WGS) and to whole-genome plus chromatin conformation (s3-GCC) yields 148- and 14.8-fold improvements, respectively, in usable reads per cell compared with sci-DNA-sequencing and sci-HiC. We show that s3-WGS and s3-GCC resolve subclonal genomic alterations in patient-derived pancreatic cancer cell lines. We expect that the s3 platform will be compatible with other transposase-based techniques, including sci-MET or CUT&Tag.


Subject(s)
Chromatin , Transposases , Animals , Chromatin/genetics , DNA/genetics , Genome , High-Throughput Nucleotide Sequencing/methods , Humans , Mice , Sequence Analysis, DNA , Single-Cell Analysis/methods , Transposases/genetics , Transposases/metabolism
18.
Laryngoscope ; 131(9): 2106-2111, 2021 09.
Article in English | MEDLINE | ID: mdl-34043247

ABSTRACT

OBJECTIVES/HYPOTHESIS: Speech recognition with a cochlear implant (CI) tends to be better for younger adults than older adults. However, older adults may take longer to reach asymptotic performance than younger adults. The present study aimed to characterize speech recognition as a function of age at implantation and listening experience for adult CI users. STUDY DESIGN: Retrospective review. METHODS: A retrospective review identified 352 adult CI recipients (387 ears) with at least 5 years of device listening experience. Speech recognition, as measured with consonant-nucleus-consonant (CNC) words in quiet and AzBio sentences in a 10-talker noise masker (10 dB signal-to-noise ratio), was reviewed at 1, 5, and 10 years postactivation. RESULTS: Speech recognition was better in younger listeners, and performance was stable or continued to improve through 10 years of CI listening experience. There was no indication of differences in acclimatization as a function of age at implantation. For the better performing CI recipients, an effect of age at implantation was more apparent for sentence recognition in noise than for word recognition in quiet. CONCLUSIONS: Adult CI recipients across the age range examined here experience speech recognition benefit with a CI. However, older adults perform more poorly than young adults for speech recognition in quiet and noise, with similar age effects through 5 to 10 years of listening experience. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2106-2111, 2021.


Subject(s)
Auditory Perception/physiology , Cochlear Implantation/methods , Cochlear Implants/statistics & numerical data , Hearing Loss, Sensorineural/surgery , Speech Perception/physiology , Adult , Age Factors , Aged , Aged, 80 and over , Cochlear Implants/adverse effects , Hearing Loss, Sensorineural/diagnosis , Humans , Middle Aged , Noise/adverse effects , Noise/prevention & control , Retrospective Studies , Signal-To-Noise Ratio , Young Adult
19.
Otol Neurotol ; 42(1): 197-202, 2021 01.
Article in English | MEDLINE | ID: mdl-33885267

ABSTRACT

BACKGROUND: The default mapping procedure for electric-acoustic stimulation (EAS) devices uses the cochlear implant recipient's unaided detection thresholds in the implanted ear to derive the acoustic settings and assign the lowest frequency filter of electric stimulation. Individual differences for speech recognition with EAS may be due to discrepancies between the electric frequency filters of individual electrode contacts and the cochlear place of stimulation, known as a frequency-to-place mismatch. Frequency-to-place mismatch of greater than 1/2 octave has been demonstrated in up to 60% of EAS users. Aligning the electric frequency filters via a place-based mapping procedure using postoperative imaging may improve speech recognition with EAS. METHODS: Masked sentence recognition was evaluated for normal-hearing subjects (n = 17) listening with vocoder simulations of EAS, using a place-based map and a default map. Simulation parameters were based on audiometric and imaging data from a representative 24-mm electrode array recipient and EAS user. The place-based map aligned electric frequency filters with the cochlear place frequency, which introduced a gap between the simulated acoustic and electric output. The default map settings were derived from the clinical programming software and provided the full speech frequency range. RESULTS: Masked sentence recognition was significantly better for simulated EAS with the place-based map as compared with the default map. CONCLUSION: The simulated EAS place-based map supported better performance than the simulated EAS default map. This indicates that individualizing maps may improve performance in EAS users by helping them achieve better asymptotic performance earlier and mitigate the need for acclimatization.


Subject(s)
Cochlear Implantation , Cochlear Implants , Speech Perception , Acoustic Stimulation , Acoustics , Auditory Threshold , Electric Stimulation , Humans , Noise
20.
J Hered ; 112(4): 377-384, 2021 07 15.
Article in English | MEDLINE | ID: mdl-33882130

ABSTRACT

The Andean bear is the only extant member of the Tremarctine subfamily and the only extant ursid species to inhabit South America. Here, we present an annotated de novo assembly of a nuclear genome from a captive-born female Andean bear, Mischief, generated using a combination of short and long DNA and RNA reads. Our final assembly has a length of 2.23 Gb, and a scaffold N50 of 21.12 Mb, contig N50 of 23.5 kb, and BUSCO score of 88%. The Andean bear genome will be a useful resource for exploring the complex phylogenetic history of extinct and extant bear species and for future population genetics studies of Andean bears.


Subject(s)
Ursidae , Animals , Cell Nucleus , Female , Genome , Molecular Sequence Annotation , Phylogeny , South America , Ursidae/genetics
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