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Article ; Online: All about Down syndrome ALL.

Gu, Zhaohui / Izraeli, Shai

2023 Volume 142, Issue 2, Page(s) 126–128

MeSH term(s)	Humans ; Down Syndrome/complications ; Down Syndrome/genetics ; Genomics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023020508
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Article: PAX5

Jia, Zhilian / Gu, Zhaohui

Frontiers in oncology

2022 Volume 12, Page(s) 1023606

Abstract: PAX5, a master regulator of B cell development and maintenance, is one of the most common targets of genetic alterations in B-cell acute lymphoblastic leukemia (B-ALL). ...

Abstract	PAX5, a master regulator of B cell development and maintenance, is one of the most common targets of genetic alterations in B-cell acute lymphoblastic leukemia (B-ALL).
Language	English
Publishing date	2022-10-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.1023606
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Article ; Online: Ph-like acute lymphoblastic leukemia in adults: understanding pathogenesis, improving outcomes, and future directions for therapy.

Aldoss, Ibrahim / Gu, Zhaohui / Afkhami, Michelle / Mokhtari, Sally / Pullarkat, Vinod

Leukemia & lymphoma

2023 Volume 64, Issue 6, Page(s) 1092–1101

Abstract: Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subgroup of B cell ALL with distinct genotypes, unified by gene expression profile similar to Ph-positive ALL, but lacking ... ...

Abstract	Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk subgroup of B cell ALL with distinct genotypes, unified by gene expression profile similar to Ph-positive ALL, but lacking the
MeSH term(s)	Humans ; Adult ; Philadelphia Chromosome ; Philadelphia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Remission Induction ; Protein Kinase Inhibitors/therapeutic use
Chemical Substances	Protein Kinase Inhibitors
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2023.2197538
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Article: MD-ALL: an Integrative Platform for Molecular Diagnosis of B-cell Acute Lymphoblastic Leukemia.

Gu, Zhaohui / Hu, Zunsong / Jia, Zhilian / Liu, Jiangyue / Mao, Allen / Han, Helen

Research square

2023

Abstract: B-cell acute lymphoblastic leukemia (B-ALL) consists of dozens of subtypes defined by distinct gene expression profiles (GEPs) and various genetic lesions. With the application of transcriptome sequencing (RNA-seq), multiple novel subtypes have been ... ...

Abstract	B-cell acute lymphoblastic leukemia (B-ALL) consists of dozens of subtypes defined by distinct gene expression profiles (GEPs) and various genetic lesions. With the application of transcriptome sequencing (RNA-seq), multiple novel subtypes have been identified, which lead to an advanced B-ALL classification and risk-stratification system. However, the complexity of analyzing RNA-seq data for B-ALL classification hinders the implementation of the new B-ALL taxonomy. Here, we introduce MD-ALL (Molecular Diagnosis of ALL), a user-friendly platform featuring sensitive and accurate B-ALL classification based on GEPs and sentinel genetic alterations. In this study, we systematically analyzed 2,955 B-ALL RNA-seq samples and generated a reference dataset representing all the reported B-ALL subtypes. Using multiple machine learning algorithms, we identified the feature genes and then established highly accurate models for B-ALL classification using either bulk or single-cell RNA-seq data. Importantly, this platform integrates the key genetic lesions, including sequence mutations, large-scale copy number variations, and gene rearrangements, to perform comprehensive and definitive B-ALL classification. Through validation in a hold-out cohort of 974 samples, our models demonstrated superior performance for B-ALL classification compared with alternative tools. In summary, MD-ALL is a user-friendly B-ALL classification platform designed to enable integrative, accurate, and comprehensive B-ALL subtype classification.
Language	English
Publishing date	2023-04-14
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2798895/v1
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Article ; Online: The effect of human umbilical cord mesenchymal stem cell-derived exosomes on diabetic retinal neurodegeneration in a rat model.

Fu, Yan / Xie, Tian-Hao / Zhang, Yue-Ling / Gu, Zhao-Hui

Journal of chemical neuroanatomy

2022 Volume 126, Page(s) 102181

Abstract: Objective: To investigate the effect of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exs) on diabetic retinal neurodegeneration (DRN).: Methods: Exosomes were isolated from human umbilical cord mesenchymal stem cells (hucMSC) ... ...

Abstract	Objective: To investigate the effect of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exs) on diabetic retinal neurodegeneration (DRN). Methods: Exosomes were isolated from human umbilical cord mesenchymal stem cells (hucMSC) and identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blotting (WB). Rats were intraperitoneally injected with Streptozotocin (STZ) to establish a diabetes mellitus model, and blood glucose levels and body weight were assessed. The rats were intravitreally injected with phosphate buffered saline (PBS; diabetic group) or hucMSC-Exs (hucMSC-Exs group). A control group of rats were not treated with STZ and were intravitreally injected with PBS (normal control group). Hematoxylin-eosin (HE) staining was used to observe changes in retinal structure and to count the number of retinal ganglion cells (RGCs) four weeks after intravitreal injection. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay (TUNEL) was used to detect retinal cell apoptosis. The retinal expression of p38 mitogen-activated protein kinase (p38MAPK), phosphorylated p38MAPK (p-p38MAPK), Bcl-2 and Bax was measured using WB to investigate the mechanism by which hucMSC-Exs affects DRN. Results: Using TEM, NTA and WB, hucMSC-Exs were successfully isolated. No significant change was observed after injection in the normal control group. All rats injected with STZ developed hyperglycemia. HE staining revealed that hucMSC-Exs effectively alleviated retinal structure disruption and reduced the apoptosis of RGCs (P < 0.05). Cells positive for TUNEL (TUNEL Conclusion: These findings suggest that intravitreal injection of hucMSC-Exs can reduce DRN and protect retinal structure, and that these effects are mediated through inhibition of the p38MAPK pathway.
Language	English
Publishing date	2022-10-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639443-7
ISSN	1873-6300 ; 0891-0618
ISSN (online)	1873-6300
ISSN	0891-0618
DOI	10.1016/j.jchemneu.2022.102181
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Article ; Online: MD-ALL: an integrative platform for molecular diagnosis of B-acute lymphoblastic leukemia.

Hu, Zunsong / Jia, Zhilian / Liu, Jiangyue / Mao, Allen / Han, Helen / Gu, Zhaohui

Haematologica

2023

Abstract: B-acute lymphoblastic leukemia (B-ALL) consists of dozens of subtypes defined by distinct gene expression profiles (GEPs) and various genetic lesions. With the application of transcriptome sequencing (RNA-seq), multiple novel subtypes have been ... ...

Abstract	B-acute lymphoblastic leukemia (B-ALL) consists of dozens of subtypes defined by distinct gene expression profiles (GEPs) and various genetic lesions. With the application of transcriptome sequencing (RNA-seq), multiple novel subtypes have been identified, which lead to an advanced B-ALL classification and risk-stratification system. However, the complexity of analyzing RNA-seq data for B-ALL classification hinders the implementation of the new B-ALL taxonomy. Here, we introduce MD-ALL (Molecular Diagnosis of ALL), an integrative platform featuring sensitive and accurate B-ALL classification based on GEPs and sentinel genetic alterations from RNA-seq data. In this study, we systematically analyzed 2,955 B-ALL RNA-seq samples and generated a reference dataset representing all the reported B-ALL subtypes. Using multiple machine learning algorithms, we identified the feature genes and then established highly sensitive and accurate models for B-ALL classification using either bulk or single-cell RNA-seq data. Importantly, this platform integrates multiple aspects of key genetic lesions acquired from RNAseq data, which include sequence mutations, large-scale copy number variations, and gene rearrangements, to perform comprehensive and definitive B-ALL classification. Through validation in a hold-out cohort of 974 samples, our models demonstrated superior performance for B-ALL classification compared with alternative tools. Moreover, to ensure accessibility and user-friendly navigation even for users with limited or no programming background, we developed an interactive graphical user interface for this MD-ALL platform, using the R Shiny package. In summary, MD-ALL is a user-friendly B-ALL classification platform designed to enable integrative, accurate, and comprehensive B-ALL subtype classification. MD-ALL is available from https://github.com/gu-lab20/MD-ALL.
Language	English
Publishing date	2023-11-16
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.283706
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Article ; Online: Identification of an alternative short ARID5B isoform associated with B-ALL survival.

Chalise, Jaya P / Hu, Zunsong / Li, Min / Shepphird, Jennifer K / Gu, Zhaohui / Gyawali, Purnima / Itakura, Keiichi / Larson, Garrett P

Biochemical and biophysical research communications

2024 Volume 703, Page(s) 149659

Abstract: Utilizing RNA sequence (RNA-Seq) splice junction data from a cohort of 1841 B-cell acute lymphoblastic leukemia (B-ALL) patients we define transcriptionally distinct isoforms of ARID5B, a risk-associated gene identified in genome wide association studies ...

Abstract	Utilizing RNA sequence (RNA-Seq) splice junction data from a cohort of 1841 B-cell acute lymphoblastic leukemia (B-ALL) patients we define transcriptionally distinct isoforms of ARID5B, a risk-associated gene identified in genome wide association studies (GWAS), which associate with disease survival. Short (S) and long (L) ARID5B transcripts, which differ in an encoded BAH-like chromatin interaction domain, show remarkable correlation to the isoform splicing pattern. Testing of the ARID5B proximal promoter of the S & L isoforms indicated that both are functionally independent in luciferase reporter assays. Increased short isoform expression is associated with decreased event-free and overall survival. The abundance of short and long transcripts strongly correlates to B-ALL prognostic stratification, where B-ALL subtypes with poor outcomes express a higher proportion of the S-isoform. These data demonstrate that the analysis of independent promoters and alternative splicing events are essential for improved risk stratification and a more complete understanding of disease pathology.
MeSH term(s)	Humans ; Genome-Wide Association Study ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Alternative Splicing ; RNA Splicing ; Base Sequence ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Protein Isoforms ; ARID5B protein, human ; DNA-Binding Proteins ; Transcription Factors
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2024.149659
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Article ; Online: ShinyCNV: a Shiny/R application to view and annotate DNA copy number variations

Gu, Zhaohui / Mullighan, Charles G

Bioinformatics. 2019 Jan. 01, v. 35, no. 1, p. 126-129

2019 , Page(s) 126–129

Abstract: Single nucleotide polymorphism (SNP) array is the most widely used platform to assess somatic copy number variations (CNVs) in cancer studies. Many SNP data-based CNV callers are available, however, the false positive rates from automated calling are ... ...

Abstract	Single nucleotide polymorphism (SNP) array is the most widely used platform to assess somatic copy number variations (CNVs) in cancer studies. Many SNP data-based CNV callers are available, however, the false positive rates from automated calling are commonly high, and reported breakpoints can be inaccurate. Manual review for each reported CNV by visualizing the SNP data is important, but is challenging for users lacking computational experience. To address this, we present a Shiny/R application ShinyCNV, an interactive graphical user interface to view and annotate CNVs. With this application, normalized SNP data, which includes log R ratio (LRR) and B allele frequency, can be plotted against the reported CNVs, and users can visually check the reliability of CNVs per se or adjust the incorrectly assigned breakpoints. Further, the interactive LRR spectrum panel within ShinyCNV can facilitate the process to identify commonly affected CNV regions from a group of samples, and to visually check if important focal gains/losses are missing from reported CNVs. ShinyCNV is designed to be intuitive for cancer researchers and can be easily installed for either personal use or deployed on servers to provide online service. ShinyCNV and the tutorial are freely available from https://github.com/gzhmat/ShinyCNV. Supplementary data are available at Bioinformatics online.
Keywords	DNA ; automation ; bioinformatics ; gene frequency ; single nucleotide polymorphism ; user interface
Language	English
Dates of publication	2019-0101
Size	p. 126-129
Publishing place	Oxford University Press
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	1468345-3
ISSN	1367-4811 ; 1460-2059
ISSN	1367-4811 ; 1460-2059
DOI	10.1093/bioinformatics/bty546
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Article ; Online: ShinyCNV: a Shiny/R application to view and annotate DNA copy number variations.

Gu, Zhaohui / Mullighan, Charles G

Bioinformatics (Oxford, England)

2018 Volume 35, Issue 1, Page(s) 126–129

Abstract: Motivation: Single nucleotide polymorphism (SNP) array is the most widely used platform to assess somatic copy number variations (CNVs) in cancer studies. Many SNP data-based CNV callers are available, however, the false positive rates from automated ... ...

Abstract	Motivation: Single nucleotide polymorphism (SNP) array is the most widely used platform to assess somatic copy number variations (CNVs) in cancer studies. Many SNP data-based CNV callers are available, however, the false positive rates from automated calling are commonly high, and reported breakpoints can be inaccurate. Manual review for each reported CNV by visualizing the SNP data is important, but is challenging for users lacking computational experience. To address this, we present a Shiny/R application ShinyCNV, an interactive graphical user interface to view and annotate CNVs. Results: With this application, normalized SNP data, which includes log R ratio (LRR) and B allele frequency, can be plotted against the reported CNVs, and users can visually check the reliability of CNVs per se or adjust the incorrectly assigned breakpoints. Further, the interactive LRR spectrum panel within ShinyCNV can facilitate the process to identify commonly affected CNV regions from a group of samples, and to visually check if important focal gains/losses are missing from reported CNVs. ShinyCNV is designed to be intuitive for cancer researchers and can be easily installed for either personal use or deployed on servers to provide online service. Availability and implementation: ShinyCNV and the tutorial are freely available from https://github.com/gzhmat/ShinyCNV. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Algorithms ; Computational Biology ; DNA Copy Number Variations ; Humans ; Molecular Sequence Annotation/methods ; Neoplasms/genetics ; Polymorphism, Single Nucleotide ; Reproducibility of Results ; Software
Language	English
Publishing date	2018-12-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/bty546
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Zs.A 2374: Show issues

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Article ; Online: Recurrent retinal detachment after pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment.

Fu, Yan / Xie, Tian-Hao / Gu, Zhao-Hui / Yang, Na / Geng, Ren-Fei / Zhang, Yue-Ling

International ophthalmology

2022 Volume 42, Issue 12, Page(s) 3813–3820

Abstract: Background: The recurrence of retinal detachment following rhegmatogenous retinal detachment (RRD) is a relatively common complication that can lead to reduced visual acuity and requires further surgery. The purpose of this study was to investigate the ... ...

Abstract	Background: The recurrence of retinal detachment following rhegmatogenous retinal detachment (RRD) is a relatively common complication that can lead to reduced visual acuity and requires further surgery. The purpose of this study was to investigate the risk factors and visual outcomes of recurrent RRD following pars plana vitrectomy (PPV) with silicone oil tamponade for primary RRD. Methods: This was a retrospective follow-up study of 343 eyes that underwent initial PPV surgery with silicone oil tamponade for primary RRD. Patients were divided into a recurrence group and a reattachment group. The main outcome measures included causative factors, visual outcomes related to the recurrence of RRD, and the perioperative factors most affecting the recurrence of RRD. Results: After retinal reattachment, we observed RRD recurrence after PPV for primary RRD in 42 out of 343 eyes (12.2%) during the follow-up period. Most causes of recurrence (69%) occurred within 6 months of surgery. Multivariate logistic regression analysis showed that a PVR ≥ Grade C (odds ratio [OR]: 4.015; 95% confidence interval [CI] 1.721-9.367; P = 0.001) was a significant predictor for the development of recurrent RRD. Compared with the reattachment group, the recurrence group exhibited a significant decline in best-corrected visual acuity (BCVA) at the last follow-up visit (P = 0.000). Eyes with PVR prior to primary surgery, or at the diagnosis of re-detachment, showed a worse final BCVA. Conclusions: Our analysis shows that the predominant risk factor for the recurrence of RRD is a PVR ≥ Grade C. PVR prior to primary surgery, or at the diagnosis of re-detachment, was also shown to limit the recovery of final visual acuity.
MeSH term(s)	Humans ; Retinal Detachment/diagnosis ; Retinal Detachment/etiology ; Retinal Detachment/surgery ; Vitrectomy/adverse effects ; Silicone Oils ; Retrospective Studies ; Follow-Up Studies ; Treatment Outcome
Chemical Substances	Silicone Oils
Language	English
Publishing date	2022-07-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	800087-6
ISSN	1573-2630 ; 0165-5701
ISSN (online)	1573-2630
ISSN	0165-5701
DOI	10.1007/s10792-022-02401-7
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