Publications by authors named "Jingzhe Lu"

4 Publications

  • Page 1 of 1

Chrom-Lasso: a lasso regression-based model to detect functional interactions using Hi-C data.

Brief Bioinform 2021 May 19. Epub 2021 May 19.

School of Medicine and the Tsinghua-Peking Center for Life science, Tsinghua University, Beijing, China.

Hi-C is a genome-wide assay based on Chromosome Conformation Capture and high-throughput sequencing to decipher 3D chromatin organization in the nucleus. However, computational methods to detect functional interactions utilizing Hi-C data face challenges including the correction for various sources of biases and the identification of functional interactions with low counts of interacting fragments. We present Chrom-Lasso, a lasso linear regression model that removes complex biases assumption-free and identifies functional interacting loci with increased power by combining information of local reads distribution surrounding the area of interest. We showed that interacting regions identified by Chrom-Lasso are more enriched for 5C validated interactions and functional GWAS hits than that of GOTHiC and Fit-Hi-C. To further demonstrate the ability of Chrom-Lasso to detect interactions of functional importance, we performed time-series Hi-C and RNA-seq during T cell activation and exhaustion. We showed that the dynamic changes in gene expression and chromatin interactions identified by Chrom-Lasso were largely concordant with each other. Finally, we experimentally confirmed Chrom-Lasso's finding that Erbb3 was co-regulated with distinct neighboring genes at different states during T cell activation. Our results highlight Chrom-Lasso's utility in detecting weak functional interaction between cis-regulatory elements, such as promoters and enhancers.
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http://dx.doi.org/10.1093/bib/bbab181DOI Listing
May 2021

Knockout of immunotherapy prognostic marker genes eliminates the effect of the anti-PD-1 treatment.

NPJ Precis Oncol 2021 May 7;5(1):37. Epub 2021 May 7.

Department of Basic Medical Science, School of Medicine, Tsinghua University, Beijing, China.

The efficacy of immunotherapy is largely patient-specific due to heterogeneity in tumors. Combining statistic power from a variety of immunotherapies across cancer types, we found four biological pathways significantly correlated with patient survival following immunotherapy. The expression of immunotherapy prognostic marker genes (IPMGs) in these pathways can predict the patient survival with high accuracy not only in the TCGA cohort (89.36%) but also in two other independent cohorts (80.91%), highlighting that the activity of the IPMGs can reflect the sensitivity of the tumor immune microenvironment (TIME) to immunotherapies. Using mouse models, we show that knockout of one of the IPMGs, MALT1, which is critical for the T-cell receptor signaling, can eliminate the antitumor effect of anti-PD-1 treatment completely by impairing the activation of CD8 T cells. Notably, knockout of another IPMG, CLEC4D, a C-type lectin receptor that expressed on myeloid cells, also reduced the effect of anti-PD-1 treatment potentially through maintaining the immunosuppressive effects of myeloid cells. Our results suggest that priming TIME via activating the IPMGs may increase the response rate and the effect of immune checkpoint blockers.
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http://dx.doi.org/10.1038/s41698-021-00175-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105367PMC
May 2021

Clinical practicality of the dizziness handicap inventory for evaluating dizziness in the Mandarin Chinese-speaking population: a prospective cross-sectional analysis.

Int J Audiol 2020 Nov 9:1-7. Epub 2020 Nov 9.

Department of Otolaryngology-Head and Neck Surgery, Hearing center/Hearing & Speech Science Laboratory, West China Hospital of Medicine Sichuan University, Chengdu, China.

Objective: To explore the clinical practicality of the dizziness handicap inventory (DHI) in the Mandarin Chinese-speaking population and compare patients' and physicians' assessments of the impact of dizziness on the quality of life using the DHI.

Design: Prospective cross-sectional.

Study Sample: Overall, 144 consecutive patients aged ≥ 18 years seeking treatment for dizziness in an Ear-Nose-Throat clinic in China.

Results: Some items in the DHI could not be completed by both patients (46/144, 31.9%) and physicians (26/144, 18.1%). In fully completed DHIs (98/144, 68.1%), the patients' self-assessment scores were higher than the physicians' assessment scores (average 44.04 ± 21.38 vs 35.94 ± 16.99; < 0.05). The strength of the correlation between the patients' and physicians' total DHI scores was high ( = 0.80; < 0.05). Moreover, at a cut-off point of 18, the discrepancy scores of 77.6% (76/98) of the cases did not exceed the minimum detectable change (MDC) of the DHI.

Conclusions: The clinical practicality of the DHI in such settings requires improvement. Even though physician interviews can increase the degree of questionnaire completion, not all items can be completed. Although the physicians' assessment scores were lower than the patients' self-assessment scores, the majority of the discordancy scores were within the MDC of the DHI.
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http://dx.doi.org/10.1080/14992027.2020.1839677DOI Listing
November 2020

Investigation on chronic tinnitus efficacy of combination of non-repetitive preferred music and educational counseling: a preliminary study.

Eur Arch Otorhinolaryngol 2020 Sep 5. Epub 2020 Sep 5.

Hearing Center/Hearing and Speech Science Laboratory, Department of Otolaryngology/Head and Neck Surgery, West China Hospital of Sichuan University, Chengdu, China.

Purpose: To improve the efficacy of music therapy on tinnitus relief, specific music that was not repetitively played and satisfies individualized preference was developed. The aim of this study was to investigate effects of combination of the specific music and educational counseling on tinnitus relief in short term.

Methods: Sixty patients suffering from chronic tinnitus were included. The non-randomized controlled study was designed with two intervention groups: educational counseling (EC, which included a 1-h individualized instruction) and preferred music therapy [PMT, which included EC plus 15, 30-min preferred music sessions (PMS)]. Three assessments-the Chinese-Mandarin version of Tinnitus Handicap Inventory (THI-CM), Tinnitus Evaluation Questionnaire (TEQ), and Visual Analogue Scale (VAS) were administered before and 1, 2, 3 weeks after initiation of treatment to evaluate the efficacy.

Results: Twenty-six patients in PMT group attained a clinically meaningful improvement in THI compared to 15 in the EC group, though both groups achieved a statistically relevant reduction in the 3 assessments.

Conclusion: The PMT had a positive impact on chronic tinnitus and related distress in a short term. It outperformed the separate EC, which is an appropriate treatment option in clinic. Therefore, it presents a possible complement to the therapeutic spectrum in chronic tinnitus.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900022624. Registered on 19 April 2019.
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http://dx.doi.org/10.1007/s00405-020-06340-wDOI Listing
September 2020