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Article ; Online: Transcriptomic analysis identifies four novel receptors potentially linking endometrial cancer with polycystic ovary syndrome and generates a transcriptomic atlas.

Alqutami, Fatma / Hachim, Mahmood / Hodgman, Charlie / Atiomo, William

2023 Volume 14, Page(s) 825–835

Abstract: Polycystic Ovary Syndrome (PCOS) is associated with a 3 to 4-fold increased risk of endometrial cancer (EC), but molecular mechanisms are unclear. Upregulation of the IGF1 gene in PCOS endometrium may increase EC risk, but this is uncertain. We aimed to ... ...

Abstract	Polycystic Ovary Syndrome (PCOS) is associated with a 3 to 4-fold increased risk of endometrial cancer (EC), but molecular mechanisms are unclear. Upregulation of the IGF1 gene in PCOS endometrium may increase EC risk, but this is uncertain. We aimed to investigate links between EC and PCOS, by analysing publicly available transcriptomic data. The NCBI Gene Expression Omnibus was used to identify relevant studies. Differentially expressed genes (DEGs) were identified and analysed using Metascape to identify pathways of interest. PCOS DEGs that encode proteins secreted into blood were identified using the Human Protein Atlas blood protein database. EC DEGs that are cellular receptors were identified using EcoTyper. These were intersected to identify which EC receptors interact with PCOS secreted proteins. Seven receptors were identified in EC but only PTPRF, ITGA2, ITGA3 and ITGB4 genes were expressed on epithelial cells. Pathway enrichment of these genes showed that the major and common pathway involved was that of the PI3K-AKT signalling pathway which was consistent with a link between PCOS and EC. However, IGF1 was down regulated in PCOS and EC. These findings hold significant promise for improving our understanding of mechanistic pathways leading to EC in PCOS.
MeSH term(s)	Female ; Humans ; Transcriptome ; Phosphatidylinositol 3-Kinases ; Polycystic Ovary Syndrome/genetics ; Gene Expression Profiling ; Endometrial Neoplasms/genetics ; Ascomycota
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.28513
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: In Silico Analysis of Publicly Available Transcriptomic Data for the Identification of Triple-Negative Breast Cancer-Specific Biomarkers.

Kaddoura, Rachid / Alqutami, Fatma / Asbaita, Mohamed / Hachim, Mahmood

Life (Basel, Switzerland)

2023 Volume 13, Issue 2

Abstract: Background: Breast cancer is the most common type of cancer among women and is classified into multiple subtypes. Triple-negative breast cancer (TNBC) is the most aggressive subtype, with high mortality rates and limited treatment options such as ... ...

Abstract	Background: Breast cancer is the most common type of cancer among women and is classified into multiple subtypes. Triple-negative breast cancer (TNBC) is the most aggressive subtype, with high mortality rates and limited treatment options such as chemotherapy and radiation. Due to the heterogeneity and complexity of TNBC, there is a lack of reliable biomarkers that can be used to aid in the early diagnosis and prognosis of TNBC in a non-invasive screening method. Aim: This study aims to use in silico methods to identify potential biomarkers for TNBC screening and diagnosis, as well as potential therapeutic markers. Methods: Publicly available transcriptomic data of breast cancer patients published in the NCBI's GEO database were used in this analysis. Data were analyzed with the online tool GEO2R to identify differentially expressed genes (DEGs). Genes that were differentially expressed in more than 50% of the datasets were selected for further analysis. Metascape, Kaplan-Meier plotter, cBioPortal, and the online tool TIMER were used for functional pathway analysis to identify the biological role and functional pathways associated with these genes. Breast Cancer Gene-Expression Miner v4.7 was used to validify the obtained results in a larger cohort of datasets. Results: A total of 34 genes were identified as differentially expressed in more than half of the datasets. The DEG GATA3 had the highest degree of regulation, and it plays a role in regulating other genes. The estrogen-dependent pathway was the most enriched pathway, involving four crucial genes, including GATA3. The gene FOXA1 was consistently down-regulated in TNBC in all datasets. Conclusions: The shortlisted 34 DEGs will aid clinicians in diagnosing TNBC more accurately as well as developing targeted therapies to improve patient prognosis. In vitro and in vivo studies are further recommended to validate the results of the current study.
Language	English
Publishing date	2023-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13020422
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Article: Deciphering the Role of Insulin-Like Growth Factor 1 in Endometrial Cancer in Patients With Polycystic Ovary Syndrome: Protocol for a Methodological Approach Using Cell Culture Experiments.

Atiomo, William / Alqutami, Fatma / Albasha, Sara / Hachim, Mahmood

JMIR research protocols

2023 Volume 12, Page(s) e48127

Abstract: Background: Endometrial cancer (EC) is the most common gynecological cancer in women globally. It is linked to increasing obesity rates and longer life spans. The molecular mechanisms leading to EC are unclear; however, women with polycystic ovary ... ...

Abstract	Background: Endometrial cancer (EC) is the most common gynecological cancer in women globally. It is linked to increasing obesity rates and longer life spans. The molecular mechanisms leading to EC are unclear; however, women with polycystic ovary syndrome (PCOS) have a 3- to 5-fold increased EC risk. According to a pilot study conducted in the United Kingdom, insulin-like growth factor-1 (IGF-1) gene and protein were raised in the endometrium and blood of women with EC and PCOS, compared with those without PCOS (controls). Therefore, raised serum IGF-1 levels may contribute to an increased EC risk in women with PCOS, but it is necessary to test this hypothesis since not all studies have demonstrated this association. Objective: This study aims to investigate the role of IGF-1 in mediating EC risk in PCOS. This will be achieved by evaluating the proliferative effects of PCOS serum, IGF-1, and IGF-1 antagonist on human endometrial cancer 1-A and 1-B cell lines, with a comparison to controls (using serum from women without PCOS and cell culture media). The study will also identify differentially expressed genes and pathways activated by various treatments. Methods: We intend to recruit 20 women with PCOS and 20 women without PCOS for this cross-sectional study. All experiments will be carried out 4 times to ensure consistency. We will perform transcriptomic and phosphoproteomic profiling to identify differentially expressed genes and phosphoproteins between different treatments using RNA sequencing and phosphoproteomics. We will also perform bioinformatics pathway analysis to identify whether any unique collection of genes or phosphoproteins explains increased EC risk in PCOS. The primary outcome measure will be the cell proliferation (growth) difference measured by cell index values. Our protocol stands out due to its unique approach; no previous study has used this approach to investigate the oncogenic effect of serum from women with PCOS. Additionally, no previous study has considered the differential mutations of genes related to the insulin signaling pathway across various types of human EC cell lines and the potential impact of these variations on their experimental findings. Results: Participants are currently being recruited. It is expected that preliminary findings suitable for analysis and publication will be available by the summer of 2024. Conclusions: Although we currently do not have any results to report, sharing our protocol at this stage will aid in research collaboration, provide an opportunity for early feedback, and help reduce duplication of effort by other research groups. The findings of our study will have broader implications. A deeper understanding of the mechanisms underlying the regulation of the IGF system in PCOS and EC will improve our ability to develop effective treatment modalities for EC and will be a vital step toward reducing EC in women globally. International registered report identifier (irrid): DERR1-10.2196/48127.
Language	English
Publishing date	2023-11-21
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2719222-2
ISSN	1929-0748
ISSN	1929-0748
DOI	10.2196/48127
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Article: COVID-19 Transcriptomic Atlas: A Comprehensive Analysis of COVID-19 Related Transcriptomics Datasets.

Alqutami, Fatma / Senok, Abiola / Hachim, Mahmood

Frontiers in genetics

2021 Volume 12, Page(s) 755222

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-12-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2021.755222
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Article: Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease: In-Silico Analysis.

Kaddoura, Rachid / Ghelani, Hardik / Alqutami, Fatma / Altaher, Hala / Hachim, Mahmood / Jan, Reem Kais

Life (Basel, Switzerland)

2023 Volume 13, Issue 3

Abstract: Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, ... ...

Abstract	Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response. Methods: In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes' annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes. Results: 174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group. Conclusions: We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.
Language	English
Publishing date	2023-03-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13030680
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Article ; Online: Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease

Rachid Kaddoura / Hardik Ghelani / Fatma Alqutami / Hala Altaher / Mahmood Hachim / Reem Kais Jan

Life, Vol 13, Iss 680, p

In-Silico Analysis

2023 Volume 680

Abstract	Background: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response. Methods: In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes’ annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes. Results: 174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group. Conclusions: We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.
Keywords	inflammatory bowel disease ; in-silico ; transcriptomics ; differentially expressed gene analysis ; infliximab treatment response ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The Role of Systems Biology in Deciphering Asthma Heterogeneity.

Hachim, Mahmood Yaseen / Alqutami, Fatma / Hachim, Ibrahim Yaseen / Heialy, Saba Al / Busch, Hauke / Hamoudi, Rifat / Hamid, Qutayba

Life (Basel, Switzerland)

2022 Volume 12, Issue 10

Abstract: Asthma is one of the most common and lifelong and chronic inflammatory diseases characterized by inflammation, bronchial hyperresponsiveness, and airway obstruction episodes. It is a heterogeneous disease of varying and overlapping phenotypes with many ... ...

Abstract	Asthma is one of the most common and lifelong and chronic inflammatory diseases characterized by inflammation, bronchial hyperresponsiveness, and airway obstruction episodes. It is a heterogeneous disease of varying and overlapping phenotypes with many confounding factors playing a role in disease susceptibility and management. Such multifactorial disorders will benefit from using systems biology as a strategy to elucidate molecular insights from complex, quantitative, massive clinical, and biological data that will help to understand the underlying disease mechanism, early detection, and treatment planning. Systems biology is an approach that uses the comprehensive understanding of living systems through bioinformatics, mathematical, and computational techniques to model diverse high-throughput molecular, cellular, and the physiologic profiling of healthy and diseased populations to define biological processes. The use of systems biology has helped understand and enrich our knowledge of asthma heterogeneity and molecular basis; however, such methods have their limitations. The translational benefits of these studies are few, and it is recommended to reanalyze the different studies and omics in conjugation with one another which may help understand the reasons for this variation and help overcome the limitations of understanding the heterogeneity in asthma pathology. In this review, we aim to show the different factors that play a role in asthma heterogeneity and how systems biology may aid in understanding and deciphering the molecular basis of asthma.
Language	English
Publishing date	2022-10-08
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12101562
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Article ; Online: The Role of Systems Biology in Deciphering Asthma Heterogeneity

Mahmood Yaseen Hachim / Fatma Alqutami / Ibrahim Yaseen Hachim / Saba Al Heialy / Hauke Busch / Rifat Hamoudi / Qutayba Hamid

Life, Vol 12, Iss 10, p

2022 Volume 1562

Abstract	Asthma is one of the most common and lifelong and chronic inflammatory diseases characterized by inflammation, bronchial hyperresponsiveness, and airway obstruction episodes. It is a heterogeneous disease of varying and overlapping phenotypes with many confounding factors playing a role in disease susceptibility and management. Such multifactorial disorders will benefit from using systems biology as a strategy to elucidate molecular insights from complex, quantitative, massive clinical, and biological data that will help to understand the underlying disease mechanism, early detection, and treatment planning. Systems biology is an approach that uses the comprehensive understanding of living systems through bioinformatics, mathematical, and computational techniques to model diverse high-throughput molecular, cellular, and the physiologic profiling of healthy and diseased populations to define biological processes. The use of systems biology has helped understand and enrich our knowledge of asthma heterogeneity and molecular basis; however, such methods have their limitations. The translational benefits of these studies are few, and it is recommended to reanalyze the different studies and omics in conjugation with one another which may help understand the reasons for this variation and help overcome the limitations of understanding the heterogeneity in asthma pathology. In this review, we aim to show the different factors that play a role in asthma heterogeneity and how systems biology may aid in understanding and deciphering the molecular basis of asthma.
Keywords	asthma ; systems biology ; multi-omics ; Science ; Q
Subject code	501
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Antimicrobial Activity of Phytic Acid: An Emerging Agent in Endodontics.

Nassar, Rania / Nassar, Mohannad / Vianna, Morgana E / Naidoo, Nerissa / Alqutami, Fatma / Kaklamanos, Eleftherios G / Senok, Abiola / Williams, David

Frontiers in cellular and infection microbiology

2021 Volume 11, Page(s) 753649

Abstract: Background: Phytic acid (IP6) is a promising and emerging agent, and because of its unique structure and distinctive properties, it lends itself to several applications in dentistry. Recently, IP6 was proposed as a potential chelating agent in ... ...

Abstract	Background: Phytic acid (IP6) is a promising and emerging agent, and because of its unique structure and distinctive properties, it lends itself to several applications in dentistry. Recently, IP6 was proposed as a potential chelating agent in endodontics. However, there is limited knowledge regarding its antimicrobial and antibiofilm effectiveness. The aims of this study, were therefore to evaluate the antimicrobial and antibiofilm activities of IP6 against a range of microbial species and compare these with ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite (NaOCl). The contact time required for IP6 to exert its bactericidal effect on Methods: The inhibitory and biocidal activities of IP6, EDTA and NaOCl were assessed using a broth microdilution assay against 11 clinical and reference strains of bacteria and a reference strain of Results: IP6 was biocidal against all tested microorganisms. At concentrations of 0.5%, 1% and 2%, IP6 required 5 min to exert a bactericidal effect on
MeSH term(s)	Anti-Infective Agents/pharmacology ; Biofilms ; Endodontics ; Enterococcus faecalis ; Microbial Sensitivity Tests ; Phytic Acid/pharmacology ; Sodium Hypochlorite
Chemical Substances	Anti-Infective Agents ; Phytic Acid (7IGF0S7R8I) ; Sodium Hypochlorite (DY38VHM5OD)
Language	English
Publishing date	2021-10-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2021.753649
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Article ; Online: Metagenomic Sequencing and Reverse Transcriptase PCR Reveal That Mobile Phones and Environmental Surfaces Are Reservoirs of Multidrug-Resistant Superbugs and SARS-CoV-2.

Boucherabine, Syrine / Nassar, Rania / Zaher, Shroque / Mohamed, Lobna / Olsen, Matthew / Alqutami, Fatma / Hachim, Mahmood / Alkhaja, Abdulmajeed / Campos, Mariana / Jones, Peter / McKirdy, Simon / Alghafri, Rashed / Tajouri, Lotti / Senok, Abiola

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 806077

Abstract: Background: Mobile phones of healthcare workers (HCWs) can act as fomites in the dissemination of microbes. This study was carried out to investigate microbial contamination of mobile phones of HCWs and environmental samples from the hospital unit using ...

Abstract	Background: Mobile phones of healthcare workers (HCWs) can act as fomites in the dissemination of microbes. This study was carried out to investigate microbial contamination of mobile phones of HCWs and environmental samples from the hospital unit using a combination of phenotypic and molecular methods. Methods: This point prevalence survey was carried out at the Emergency unit of a tertiary care facility. The emergency unit has two zones, a general zone for non-COVID-19 patients and a dedicated COVID-19 zone for confirmed or suspected COVID-19 patients. Swabs were obtained from the mobile phones of HCWs in both zones for bacterial culture and shotgun metagenomic analysis. Metagenomic sequencing of pooled environmental swabs was conducted. RT-PCR for SARS-CoV-2 detection was carried out. Results: Bacteria contamination on culture was detected from 33 (94.2%) mobile phones with a preponderance of Conclusion: The findings demonstrate that mobile phones of HCWs are fomites for potentially pathogenic and highly drug-resistant microbes. The presence of these microbes on the mobile phones and hospital environmental surfaces is a concern as it poses a risk of pathogen transfer to patients and dissemination into the community.
MeSH term(s)	COVID-19 ; Cell Phone ; Humans ; Methicillin-Resistant Staphylococcus aureus/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; SARS-CoV-2/genetics
Language	English
Publishing date	2022-03-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.806077
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