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Article: Turning genome-wide association study findings into opportunities for drug repositioning.

Lau, Alexandria / So, Hon-Cheong

Computational and structural biotechnology journal

2020 Volume 18, Page(s) 1639–1650

Abstract: Drug development is a very costly and lengthy process, while repositioned or repurposed drugs could be brought into clinical practice within a shorter time-frame and at a much reduced cost. Numerous computational approaches to drug repositioning have ... ...

Abstract	Drug development is a very costly and lengthy process, while repositioned or repurposed drugs could be brought into clinical practice within a shorter time-frame and at a much reduced cost. Numerous computational approaches to drug repositioning have been developed, but methods utilizing genome-wide association studies (GWASs) data are less explored. The past decade has observed a massive growth in the amount of data from GWAS; the rich information contained in GWAS has great potential to guide drug repositioning or discovery. While multiple tools are available for finding the most relevant genes from GWAS hits, searching for top susceptibility genes is only one way to guide repositioning, which has its own limitations. Here we provide a comprehensive review of different computational approaches that employ GWAS data to guide drug repositioning. These methods include selecting top candidate genes from GWAS as drug targets, deducing drug candidates based on drug-drug and disease-disease similarities, searching for reversed expression profiles between drugs and diseases, pathway-based methods as well as approaches based on analysis of biological networks. Each method is illustrated with examples, and their respective strengths and limitations are discussed. We also discussed several areas for future research.
Language	English
Publishing date	2020-06-12
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2020.06.015
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The impact of COVID-19 on beekeepers in Texas and Louisiana

Lau, Pierre / Payne, Alexandria N. / Khan, Omar / Buchman, Mary Beth / Rangel, Juliana

Journal of apicultural research. 2022 May 5, v. 61, no. 3

2022

Abstract: The COVID-19 pandemic has impacted just about every aspect of society, including apiculture-related activities. A recent survey found that honey bee-related research has been negatively impacted by the pandemic on a global scale. However, to our ... ...

Abstract	The COVID-19 pandemic has impacted just about every aspect of society, including apiculture-related activities. A recent survey found that honey bee-related research has been negatively impacted by the pandemic on a global scale. However, to our knowledge, no study has yet explored how it has impacted beekeepers and their apiculture-related activities in the United States. For this reason, we conducted a survey of commercial, sideliner, and hobbyist beekeepers across Texas and Louisiana (n = 217) to determine whether and how COVID-19 impacted their beekeeping operations in 2020. Approximately half of all surveyed beekeepers answered that the COVID-19 pandemic had an overall negative impact on their beekeeping operations, while the other half reported no impact. There were differences in the types of responses among beekeeper classes, with hobbyist and sideliner beekeepers reporting more negative impacts on their beekeeping activities compared to commercial beekeepers. According to our survey data, the apiculture categories that were most negatively impacted by the pandemic were participation in beekeeper meetings, workshops, and conferences (∼75% of respondents reported a negative impact), as well as involvement in beekeeping-related programs such as outreach and mentorship opportunities (∼67%). However, for most of the other surveyed categories, the majority of beekeepers reported that the COVID-19 pandemic had no impact on their beekeeping activities/operations. This study gives us a better understanding of how apiculture has been impacted by the pandemic in the United States and how beekeepers faired in their operations during 2020.
Keywords	COVID-19 infection ; apiculture ; beekeepers ; honey ; outreach ; pandemic ; research ; surveys ; Louisiana ; Texas
Language	English
Dates of publication	2022-0505
Size	p. 309-314.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	281228-9
ISSN	2078-6913 ; 0021-8839
ISSN (online)	2078-6913
ISSN	0021-8839
DOI	10.1080/00218839.2022.2051333
Database	NAL-Catalogue (AGRICOLA)

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Article: The impact of COVID-19 on beekeepers in Texas and Louisiana

Lau, Pierre / Payne, Alexandria N. / Khan, Omar / Buchman, Mary Beth / Rangel, Juliana

Journal of apicultural research

2022 Volume 61, Issue 3, Page(s) 309

Language	English
Document type	Article
ZDB-ID	281228-9
ISSN	0021-8839
Database	Current Contents Nutrition, Environment, Agriculture

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Article ; Online: Exploring Diseases/Traits and Blood Proteins Causally Related to Expression of ACE2, the Putative Receptor of SARS-CoV-2: A Mendelian Randomization Analysis Highlights Tentative Relevance of Diabetes-Related Traits.

Rao, Shitao / Lau, Alexandria / So, Hon-Cheong

Diabetes care

2020 Volume 43, Issue 7, Page(s) 1416–1426

Abstract: Objective: COVID-19 has become a major public health problem. There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of : Research design and methods: We conducted a phenome-wide MR study to prioritize diseases/traits and ... ...

Abstract	Objective: COVID-19 has become a major public health problem. There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of Research design and methods: We conducted a phenome-wide MR study to prioritize diseases/traits and blood proteins causally linked to Results: The most consistent finding was tentative evidence of an association between diabetes-related traits and increased Conclusions: Our analysis suggested that diabetes and related traits may increase
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Betacoronavirus/metabolism ; COVID-19 ; Coronavirus Infections/metabolism ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/metabolism ; Receptors, Virus/metabolism ; SARS Virus/metabolism ; SARS-CoV-2
Chemical Substances	Receptors, Virus ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-05-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc20-0643
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1434: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Disinfection Byproduct Recovery during Extraction and Concentration in Preparation for Chemical Analyses or Toxicity Assays.

Lau, Stephanie S / Forster, Alexandria L / Richardson, Susan D / Mitch, William A

Environmental science & technology

2021 Volume 55, Issue 20, Page(s) 14136–14145

Abstract: Over 700 disinfection byproducts (DBPs) have been identified, but they account for only ∼30% of total organic halogen (TOX). Extracting disinfected water is necessary to assess the overall toxicity of both known and unknown DBPs. Commonly used DBP ... ...

Abstract	Over 700 disinfection byproducts (DBPs) have been identified, but they account for only ∼30% of total organic halogen (TOX). Extracting disinfected water is necessary to assess the overall toxicity of both known and unknown DBPs. Commonly used DBP extraction methods include liquid-liquid extraction (LLE) and solid-phase extraction (SPE), which may use either XAD resins or other polymeric sorbents. With few exceptions, DBP recoveries have not been quantified. We compared recoveries by LLE, XAD resins, and a mixture of Phenomenex Sepra SPE sorbents (hereafter SPE) for (semi-)volatile DBPs and nonvolatile model compounds at the 1-L scale. We scaled up the three methods to extract DBPs in 10 L of chlorinated creek waters. For (semi-)volatile DBPs, XAD resulted in lower recoveries than LLE and SPE at both 1- and 10-L scales. At the 10-L scale, recovery of certain trihalomethanes and trihalogenated haloacetic acids by XAD was negligible, while recovery of other (semi-)volatile DBPs extracted by XAD (<30%) was lower than by SPE or LLE (30-60%). TOX recovery at the 10-L scale was generally similar by the three extraction methods. The low TOX recovery (<30%) indicates that the toxicity assessed by bioassays predominantly reflects the contribution of the nonvolatile, hydrophobic fraction of DBPs.
MeSH term(s)	Disinfectants ; Disinfection ; Halogenation ; Trihalomethanes/analysis ; Water Pollutants, Chemical/analysis ; Water Purification
Chemical Substances	Disinfectants ; Trihalomethanes ; Water Pollutants, Chemical
Language	English
Publishing date	2021-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.1c04323
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: RNA Sequencing of the Tumor Microenvironment in Precision Cancer Immunotherapy.

Lau, Denise / Bobe, Alexandria M / Khan, Aly A

Trends in cancer

2019 Volume 5, Issue 3, Page(s) 149–156

Abstract: RNA sequencing (RNA-seq) provides an efficient high-throughput technique to robustly characterize the tumor immune microenvironment (TME). The increasing use of RNA-seq in clinical and basic science settings provides a powerful opportunity to access ... ...

Abstract	RNA sequencing (RNA-seq) provides an efficient high-throughput technique to robustly characterize the tumor immune microenvironment (TME). The increasing use of RNA-seq in clinical and basic science settings provides a powerful opportunity to access novel therapeutic biomarkers in the TME. Advanced computational methods are making it possible to resolve the composition of the tumor immune infiltrate, infer the immunological phenotypes of those cells, and assess the immune receptor repertoire in RNA-seq data. These immunological characterizations have increasingly important implications for guiding immunotherapy use. Here, we highlight recent studies that demonstrate the potential utility of RNA-seq in clinical settings, review key computational methods used for characterizing the TME for precision cancer immunotherapy, and discuss important considerations in data interpretation and current technological limitations.
MeSH term(s)	Biomarkers, Tumor ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Lymphocytes, Tumor-Infiltrating/pathology ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/pathology ; Precision Medicine/methods ; Sequence Analysis, RNA ; Tumor Microenvironment/genetics
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2019-03-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2019.02.006
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Book ; Online: Turning genome-wide association study findings into opportunities for drug repositioning

Lau, Alexandria / So, Hon-Cheong

2019

Abstract: Drug development is a very costly and lengthy process, while repositioned or repurposed drugs could be brought into clinical practice within a shorter time-frame and at a much reduced cost. The past decade has observed a massive growth in the amount of ... ...

Abstract	Drug development is a very costly and lengthy process, while repositioned or repurposed drugs could be brought into clinical practice within a shorter time-frame and at a much reduced cost. The past decade has observed a massive growth in the amount of data from genome-wide association studies (GWAS). The rich information contained in GWAS data has great potential to guide drug discovery or repositioning. Here we provide an overview of different computational approaches which employ GWAS data to guide drug repositioning. These methods include selection of top candidate genes from GWAS as drug targets, deducing drug candidates based on drug-drug and disease-disease similarity, searching for reversed expression profiles between drugs and diseases, pathway-based methods as well as repositioning based on analysis of biological networks. Each method is illustrated with examples, and their respective strengths and limitations are discussed. Finally we discussed several areas for future research.
Keywords	Quantitative Biology - Genomics
Publishing date	2019-11-11
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Disinfection Byproduct Recovery during Extraction and Concentration in Preparation for Chemical Analyses or Toxicity Assays

Lau, Stephanie S. / Forster, Alexandria L. / Richardson, Susan D. / Mitch, William A.

Environmental science & technology. 2021 Oct. 07, v. 55, no. 20

2021

Abstract	Over 700 disinfection byproducts (DBPs) have been identified, but they account for only ∼30% of total organic halogen (TOX). Extracting disinfected water is necessary to assess the overall toxicity of both known and unknown DBPs. Commonly used DBP extraction methods include liquid–liquid extraction (LLE) and solid-phase extraction (SPE), which may use either XAD resins or other polymeric sorbents. With few exceptions, DBP recoveries have not been quantified. We compared recoveries by LLE, XAD resins, and a mixture of Phenomenex Sepra SPE sorbents (hereafter SPE) for (semi-)volatile DBPs and nonvolatile model compounds at the 1-L scale. We scaled up the three methods to extract DBPs in 10 L of chlorinated creek waters. For (semi-)volatile DBPs, XAD resulted in lower recoveries than LLE and SPE at both 1- and 10-L scales. At the 10-L scale, recovery of certain trihalomethanes and trihalogenated haloacetic acids by XAD was negligible, while recovery of other (semi-)volatile DBPs extracted by XAD (<30%) was lower than by SPE or LLE (30–60%). TOX recovery at the 10-L scale was generally similar by the three extraction methods. The low TOX recovery (<30%) indicates that the toxicity assessed by bioassays predominantly reflects the contribution of the nonvolatile, hydrophobic fraction of DBPs.
Keywords	byproducts ; disinfection ; environmental science ; halogens ; hydrophobicity ; liquid-liquid extraction ; polymers ; solid phase extraction ; sorbents ; streams ; toxicity
Language	English
Dates of publication	2021-1007
Size	p. 14136-14145.
Publishing place	American Chemical Society
Document type	Article
ISSN	1520-5851
DOI	10.1021/acs.est.1c04323
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis

Rao, Shitao / Lau, Alexandria / So, Hon-Cheong

Abstract: The novel coronavirus 2019-nCoV has caused major outbreaks in many parts of the world. A better understanding of the pathophysiology of COVID-19 is urgently needed. Clinically, it is important to identify who may be susceptible to infection and identify ... ...

Abstract	The novel coronavirus 2019-nCoV has caused major outbreaks in many parts of the world. A better understanding of the pathophysiology of COVID-19 is urgently needed. Clinically, it is important to identify who may be susceptible to infection and identify treatments for the disease. There is good evidence that ACE2 is a receptor for 2019-nCoV, and studies also suggested that high expression of ACE2 may increase susceptibility to infection. Here we conducted a phenome-wide Mendelian randomization (MR) study to prioritize diseases/traits and blood proteins that may be causally linked to ACE2 expression in the lung. Expression data was based on GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR analysis, as these drugs could potentially alter ACE2 expression and may be clinically relevant. Notably, MR is much less vulnerable to confounding and reverse causality compared to observational studies. The most consistent finding was a tentative causal association between diabetes-related traits and increased ACE2 expression. Based on one of the largest GWAS on type II diabetes (T2DM) to date (N=898,130), we found that T2DM is causally linked to raised ACE2 expression (beta=0.1835, 95% CI 0.0853-0.2817; p=2.49E-4; GSMR method). Significant associations (at nominal level; p<0.05) was also observed across multiple datasets, with different analytic methods, and for both type I and II diabetes. Other diseases/traits having nominal significant associations with increased ACE2 included inflammatory bowel disease, (ER+) breast and lung cancers, asthma, smoking and elevated ALT, among others. We also uncovered a number of plasma/serum proteins potentially linked to altered ACE2 expression, and the top enriched pathways included cytokine-cytokine-receptor interaction, VEGF signaling, JAK-STAT signaling etc. We also explored drugs that target some of the top-ranked proteins in the MR analysis. In conclusion, the current MR analysis reveals diseases/traits and blood proteins that may causally affect ACE2 expression, which in turn may influence susceptibility to the infection. The proteome-wide MR analysis may shed light on the molecular mechanisms underlying ACE2 expression, and may help guide drug repositioning in the future. Nevertheless, we stress that further studies are required to verify our findings due to various limitations and the exploratory nature of some analyses.
Keywords	covid19
Publisher	MedRxiv; WHO
Document type	Article ; Online
DOI	10.1101/2020.03.04.20031237
Database	COVID19

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Article: Exploring Diseases/Traits and Blood Proteins Causally Related to Expression of ACE2, the Putative Receptor of SARS-CoV-2: A Mendelian Randomization Analysis Highlights Tentative Relevance of Diabetes-Related Traits

Rao, Shitao / Lau, Alexandria / So, Hon-Cheong

Diabetes Care

Abstract: OBJECTIVE: COVID-19 has become a major public health problem. There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of ACE2 may increase susceptibility to infection. We aimed to explore risk factors affecting susceptibility ... ...

Abstract	OBJECTIVE: COVID-19 has become a major public health problem. There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of ACE2 may increase susceptibility to infection. We aimed to explore risk factors affecting susceptibility to infection and prioritize drug repositioning candidates, based on Mendelian randomization (MR) studies on ACE2 lung expression. RESEARCH DESIGN AND METHODS: We conducted a phenome-wide MR study to prioritize diseases/traits and blood proteins causally linked to ACE2 lung expression in GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR, as these drugs may alter ACE2 expression and may be clinically relevant. RESULTS: The most consistent finding was tentative evidence of an association between diabetes-related traits and increased ACE2 expression. Based on one of the largest genome-wide association studies on type 2 diabetes mellitus (T2DM) to date (N = 898,130), T2DM was causally linked to raised ACE2 expression (P = 2.91E-03; MR-IVW). Significant associations (at nominal level; P < 0.05) with ACE2 expression were observed across multiple diabetes data sets and analytic methods for T1DM, T2DM, and related traits including early start of insulin. Other diseases/traits having nominal significant associations with increased expression included inflammatory bowel disease, (estrogen receptor-positive) breast cancer, lung cancer, asthma, smoking, and elevated alanine aminotransferase. We also identified drugs that may target the top-ranked proteins in MR, such as fostamatinib and zinc. CONCLUSIONS: Our analysis suggested that diabetes and related traits may increase ACE2 expression, which may influence susceptibility to infection (or more severe infection). However, none of these findings withstood rigorous multiple testing corrections (at false discovery rate <0.05). Proteome-wide MR analyses might help uncover mechanisms underlying ACE2 expression and guide drug repositioning. Further studies are required to verify our findings.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #324277
Database	COVID19

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