Making the genomic leap in HCT: application of second-generation sequencing to clinical advances in hematopoietic cell transplantation

Li, Yun R.; Levine, John E.; Hákonarson, Hákon; Keating, Brendan J.

doi:10.1038/ejhg.2013.247

Cited by 6 publications

(4 citation statements)

References 57 publications

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“…Accordingly, many omics applications may be used to determine optimal donor–recipient matches, as well as to monitor markers of rejection 127 . For instance, sequencing cell-free DNA can detect circulating donor DNA 128 , the levels of which are correlated with the severity of organ rejection 129 .…”

Section: Challengesmentioning

confidence: 99%

Integrative omics for health and disease

2018

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Advances in omics technologies — such as genomics, transcriptomics, proteomics and metabolomics — have begun to enable personalized medicine at an extraordinarily detailed molecular level. Individually, these technologies have contributed medical advances that have begun to enter clinical practice. However, each technology individually cannot capture the entire biological complexity of most human diseases. Integration of multiple technologies has emerged as an approach to provide a more comprehensive view of biology and disease. In this Review, we discuss the potential for combining diverse types of data and the utility of this approach in human health and disease. We provide examples of data integration to understand, diagnose and inform treatment of diseases, including rare and common diseases as well as cancer and transplant biology. Finally, we discuss technical and other challenges to clinical implementation of integrative omics.

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Section: Challengesmentioning

confidence: 99%

Integrative omics for health and disease

2018

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“…To this end, we employed RNA-seq technology to explore the molecular mechanism of 1 . RNA-seq is usually used for prenatal screening, genetic disease diagnosis, tumor mutant gene detection and targeted-therapy [20,21,22,23]. The rapid development of RNA-seq has provided a novel method to investigate the mechanisms underlying TCM, facilitating the interpretation of the effects of TCM at a molecular level.…”

Section: Discussionmentioning

confidence: 99%

Chlojaponilactone B Attenuates Lipopolysaccharide-Induced Inflammatory Responses by Suppressing TLR4-Mediated ROS Generation and NF-κB Signaling Pathway

Zheng

Zhou

et al. 2019

Molecules

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The lindenane-type sesquiterpenoid chlojaponilactone B (1), isolated from Chloranthus japonicus, has been reported to possess anti-inflammatory properties. The present study aimed to further explore the molecular mechanisms underlying the anti-inflammatory activity of 1. RNA-seq analyses revealed the significant changes in the expression levels of genes related to multiple inflammatory pathways upon treatment of lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages with 1. Real time PCR (RT-PCR) and Western blotting were used to confirm the modulations in the expression of essential molecules related to inflammatory responses. Compound 1 inhibited toll like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) activation upon LPS stimulation, influencing the expression of NF-κB and pro-inflammatory mediators. Molecular docking studies showed that 1 bound to TLR4 in a manner similar to that of TAK-242, a TLR4 inhibitor. Moreover, our results showed that 1 suppressed inflammatory responses by inhibiting TLR4 and subsequently decreasing reactive oxygen species (ROS) generation, downregulating the NF-κB, thus reducing the expression of the pro-inflammatory cytokines iNOS, NO, COX-2, IL-6 and TNF-α; these effects were similar to those of TAK-242. We proposed that 1 should be considered as a potential anti-inflammatory compound in future research.

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“…However, in both studies, Sanger sequencing was the least sensitive method, probably because of its specific sequencing primers in contrast to the more generic primers used in SSP and rSSO. It remains to be seen how the new HLA kits based on the next generation sequencing techniques will unravel LOH, as less than 1.5%–10% of the background sequence can be assigned to another allele by these new sequencing techniques .…”

Section: Discussionmentioning

confidence: 99%

Conflicting HLA assignment by three different typing methods due to the apparent loss of heterozygosity in the MHC region

Linjama

Impola

Niittyvuopio

et al. 2016

HLA

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Loss of heterozygosity (LOH) has been reported to cause false human leukocyte antigen (HLA) homozygous typing results in pre-transplant patients suffering from haematological malignancies, who in fact are HLA heterozygous. This poses a challenge for histocompatibility testing, as a stem cell graft from a genuinely HLA homozygous donor to a mistyped patient may lead to acute life-threatening graft-vs-host disease. LOH in the HLA region on chromosome 6 is known to be quite common in solid tumours, helping malignant cells to escape T-cell surveillance, but the incidence in haematological malignancies is less well known and the estimates vary. Here we report LOH in the HLA region of five patients with haematological malignancy. We found considerable differences in sensitivity between the three different HLA typing methods used in our laboratory: SSP was clearly the most sensitive method for detecting the lost haplotype, followed by rSSO, while SBT was the least sensitive technique. A subsequent, retrospective genotyping of 65 HLA homozygous haematological patients by SSP method showed no mistyped LOH cases in our laboratory in the past 10 years. The frequency of HLA homozygosity was found to be similar between haematological patients and control groups. It is important for an HLA laboratory to be aware of the differences in various HLA typing techniques' sensitivity for detecting an under-represented haplotype between HLA typing techniques when genotyping patients with haematological diseases. It is advisable for HLA laboratories to have at least two different methods with different sensitivities in their repertoire to be able to retype samples when a false homozygous result is suspected.

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Making the genomic leap in HCT: application of second-generation sequencing to clinical advances in hematopoietic cell transplantation

Cited by 6 publications

References 57 publications

Integrative omics for health and disease

Integrative omics for health and disease

Chlojaponilactone B Attenuates Lipopolysaccharide-Induced Inflammatory Responses by Suppressing TLR4-Mediated ROS Generation and NF-κB Signaling Pathway

Conflicting HLA assignment by three different typing methods due to the apparent loss of heterozygosity in the MHC region

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