Journal of Personalized Medicine

Research

18 pages, 947 KiB

Open AccessArticle

Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach

by Sofia Galvão Feronato, Maria Luiza Matos Silva, Rafael Izbicki, Ticiana D. J. Farias, Patrícia Shigunov, Bruno Dallagiovanna, Fabio Passetti and Hellen Geremias dos Santos

J. Pers. Med. 2022, 12(8), 1330; https://doi.org/10.3390/jpm12081330 - 19 Aug 2022

Cited by 3 | Viewed by 2346

Abstract

Amyotrophic lateral sclerosis (ALS) is a multi-system neurodegenerative disease that affects both upper and lower motor neurons, resulting from a combination of genetic, environmental, and lifestyle factors. Usually, the association between single-nucleotide polymorphisms (SNPs) and this disease is tested individually, which leads to [...] Read more.

Amyotrophic lateral sclerosis (ALS) is a multi-system neurodegenerative disease that affects both upper and lower motor neurons, resulting from a combination of genetic, environmental, and lifestyle factors. Usually, the association between single-nucleotide polymorphisms (SNPs) and this disease is tested individually, which leads to the testing of multiple hypotheses. In addition, this classical approach does not support the detection of interaction-dependent SNPs. We applied a two-step procedure to select SNPs and pairwise interactions associated with ALS. SNP data from 276 ALS patients and 268 controls were analyzed by a two-step group LASSO in 2000 iterations. In the first step, we fitted a group LASSO model to a bootstrap sample and a random subset of predictors (

25 %

) from the original data set aiming to screen for important SNPs and, in the second step, we fitted a hierarchical group LASSO model to evaluate pairwise interactions. An in silico analysis was performed on a set of variables, which were prioritized according to their bootstrap selection frequency. We identified seven SNPs (rs16984239, rs10459680, rs1436918, rs1037666, rs4552942, rs10773543, and rs2241493) and two pairwise interactions (rs16984239:rs2118657 and rs16984239:rs3172469) potentially involved in nervous system conservation and function. These results may contribute to the understanding of ALS pathogenesis, its diagnosis, and therapeutic strategy improvement. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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23 pages, 12108 KiB

Open AccessArticle

Single Channel Image Enhancement (SCIE) of White Blood Cells Based on Virtual Hexagonal Filter (VHF) Designed over Square Trellis

by Shahid Rasheed, Mudassar Raza, Muhammad Sharif, Seifedine Kadry and Abdullah Alharbi

J. Pers. Med. 2022, 12(8), 1232; https://doi.org/10.3390/jpm12081232 - 28 Jul 2022

Cited by 2 | Viewed by 2075

Abstract

White blood cells (WBCs) are the important constituent of a blood cell. These blood cells are responsible for defending the body against infections. Abnormalities identified in WBC smears lead to the diagnosis of disease types such as leukocytosis, hepatitis, and immune system disorders. [...] Read more.

White blood cells (WBCs) are the important constituent of a blood cell. These blood cells are responsible for defending the body against infections. Abnormalities identified in WBC smears lead to the diagnosis of disease types such as leukocytosis, hepatitis, and immune system disorders. Digital image analysis for infection detection at an early stage can help fast and precise diagnosis, as compared to manual inspection. Sometimes, acquired blood cell smear images from an L2-type microscope are of very low quality. The manual handling, haziness, and dark areas of the image become problematic for an efficient and accurate diagnosis. Therefore, WBC image enhancement needs attention for an effective diagnosis of the disease. This paper proposed a novel virtual hexagonal trellis (VHT)-based image filtering method for WBC image enhancement and contrast adjustment. In this method, a filter named the virtual hexagonal filter (VHF), of size 3 × 3, and based on a hexagonal structure, is formulated by using the concept of the interpolation of real and square grid pixels. This filter is convolved with WBC ALL-IBD images for enhancement and contrast adjustment. The proposed filter improves the results both visually and statically. A comparison with existing image enhancement approaches proves the validity of the proposed work. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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12 pages, 2316 KiB

Open AccessArticle

Quantifying Spatial Heterogeneity of Tumor-Infiltrating Lymphocytes to Predict Survival of Individual Cancer Patients

by Aleksandra Suwalska, Lukasz Zientek, Joanna Polanska and Michal Marczyk

J. Pers. Med. 2022, 12(7), 1113; https://doi.org/10.3390/jpm12071113 - 7 Jul 2022

Cited by 3 | Viewed by 2034

Abstract

Tumor-infiltrating lymphocytes (TILs), identified on HE-stained histopathological images in the cancer area, are indicators of the adaptive immune response against cancers and play a major role in personalized cancer immunotherapy. Recent works indicate that the spatial organization of TILs may be prognostic of [...] Read more.

Tumor-infiltrating lymphocytes (TILs), identified on HE-stained histopathological images in the cancer area, are indicators of the adaptive immune response against cancers and play a major role in personalized cancer immunotherapy. Recent works indicate that the spatial organization of TILs may be prognostic of disease-specific survival and recurrence. However, there are a limited number of methods that were proposed and tested in analyses of the spatial structure of TILs. In this work, we evaluated 14 different spatial measures, including the one developed for other omics data, on 10,532 TIL maps from 23 cancer types in terms of reproducibility, uniqueness, and impact on patient survival. For each spatial measure, 16 different scenarios for the definition of prognostic factor were tested. We found no difference in survival prediction when TIL maps were stored as binary images or continuous TIL probability scores. When spatial measures were discretized into a low and high category, a higher correlation with survival was observed. Three measures with the highest cancer prognosis capability were spatial autocorrelation, GLCM M1, and closeness centrality. Most of the tested measures could be further tuned to increase prediction performance. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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24 pages, 7746 KiB

Open AccessArticle

Multi-Level Biological Network Analysis and Drug Repurposing Based on Leukocyte Transcriptomics in Severe COVID-19: In Silico Systems Biology to Precision Medicine

by Pakorn Sagulkoo, Hathaichanok Chuntakaruk, Thanyada Rungrotmongkol, Apichat Suratanee and Kitiporn Plaimas

J. Pers. Med. 2022, 12(7), 1030; https://doi.org/10.3390/jpm12071030 - 23 Jun 2022

Cited by 9 | Viewed by 4244

Abstract

The coronavirus disease 2019 (COVID-19) pandemic causes many morbidity and mortality cases. Despite several developed vaccines and antiviral therapies, some patients experience severe conditions that need intensive care units (ICU); therefore, precision medicine is necessary to predict and treat these patients using novel [...] Read more.

The coronavirus disease 2019 (COVID-19) pandemic causes many morbidity and mortality cases. Despite several developed vaccines and antiviral therapies, some patients experience severe conditions that need intensive care units (ICU); therefore, precision medicine is necessary to predict and treat these patients using novel biomarkers and targeted drugs. In this study, we proposed a multi-level biological network analysis framework to identify key genes via protein–protein interaction (PPI) network analysis as well as survival analysis based on differentially expressed genes (DEGs) in leukocyte transcriptomic profiles, discover novel biomarkers using microRNAs (miRNA) from regulatory network analysis, and provide candidate drugs targeting the key genes using drug–gene interaction network and structural analysis. The results show that upregulated DEGs were mainly enriched in cell division, cell cycle, and innate immune signaling pathways. Downregulated DEGs were primarily concentrated in the cellular response to stress, lysosome, glycosaminoglycan catabolic process, and mature B cell differentiation. Regulatory network analysis revealed that hsa-miR-6792-5p, hsa-let-7b-5p, hsa-miR-34a-5p, hsa-miR-92a-3p, and hsa-miR-146a-5p were predicted biomarkers. CDC25A, GUSB, MYBL2, and SDAD1 were identified as key genes in severe COVID-19. In addition, drug repurposing from drug–gene and drug–protein database searching and molecular docking showed that camptothecin and doxorubicin were candidate drugs interacting with the key genes. In conclusion, multi-level systems biology analysis plays an important role in precision medicine by finding novel biomarkers and targeted drugs based on key gene identification. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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12 pages, 1080 KiB

Open AccessArticle

Evolution of Protein Functional Annotation: Text Mining Study

by Ekaterina V. Ilgisonis, Pavel V. Pogodin, Olga I. Kiseleva, Svetlana N. Tarbeeva and Elena A. Ponomarenko

J. Pers. Med. 2022, 12(3), 479; https://doi.org/10.3390/jpm12030479 - 16 Mar 2022

Cited by 3 | Viewed by 2699

Abstract

Within the Human Proteome Project initiative framework for creating functional annotations of uPE1 proteins, the neXt-CP50 Challenge was launched in 2018. In analogy with the missing-protein challenge, each command deciphers the functional features of the proteins in the chromosome-centric mode. However, the neXt-CP50 [...] Read more.

Within the Human Proteome Project initiative framework for creating functional annotations of uPE1 proteins, the neXt-CP50 Challenge was launched in 2018. In analogy with the missing-protein challenge, each command deciphers the functional features of the proteins in the chromosome-centric mode. However, the neXt-CP50 Challenge is more complicated than the missing-protein challenge: the approaches and methods for solving the problem are clear, but neither the concept of protein function nor specific experimental and/or bioinformatics protocols have been standardized to address it. We proposed using a retrospective analysis of the key HPP repository, the neXtProt database, to identify the most frequently used experimental and bioinformatic methods for analyzing protein functions, and the dynamics of accumulation of functional annotations. It has been shown that the dynamics of the increase in the number of proteins with known functions are greater than the progress made in the experimental confirmation of the existence of questionable proteins in the framework of the missing-protein challenge. At the same time, the functional annotation is based on the guilty-by-association postulate, according to which, based on large-scale experiments on API-MS and Y2H, proteins with unknown functions are most likely mapped through “handshakes” to biochemical processes. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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18 pages, 8676 KiB

Open AccessArticle

CDK1 and HSP90AA1 Appear as the Novel Regulatory Genes in Non-Small Cell Lung Cancer: A Bioinformatics Approach

by Nirjhar Bhattacharyya, Samriddhi Gupta, Shubham Sharma, Aman Soni, Sali Abubaker Bagabir, Malini Bhattacharyya, Atreyee Mukherjee, Atiah H. Almalki, Mustfa F. Alkhanani, Shafiul Haque, Ashwini Kumar Ray and Md. Zubbair Malik

J. Pers. Med. 2022, 12(3), 393; https://doi.org/10.3390/jpm12030393 - 4 Mar 2022

Cited by 23 | Viewed by 4882

Abstract

Lung cancer is one of the most invasive cancers affecting over a million of the population. Non-small cell lung cancer (NSCLC) constitutes up to 85% of all lung cancer cases, and therefore, it is essential to identify predictive biomarkers of NSCLC for therapeutic [...] Read more.

Lung cancer is one of the most invasive cancers affecting over a million of the population. Non-small cell lung cancer (NSCLC) constitutes up to 85% of all lung cancer cases, and therefore, it is essential to identify predictive biomarkers of NSCLC for therapeutic purposes. Here we use a network theoretical approach to investigate the complex behavior of the NSCLC gene-regulatory interactions. We have used eight NSCLC microarray datasets GSE19188, GSE118370, GSE10072, GSE101929, GSE7670, GSE33532, GSE31547, and GSE31210 and meta-analyzed them to find differentially expressed genes (DEGs) and further constructed a protein–protein interaction (PPI) network. We analyzed its topological properties and identified significant modules of the PPI network using cytoscape network analyzer and MCODE plug-in. From the PPI network, top ten genes of each of the six topological properties like closeness centrality, maximal clique centrality (MCC), Maximum Neighborhood Component (MNC), radiality, EPC (Edge Percolated Component) and bottleneck were considered for key regulator identification. We further compared them with top ten hub genes (those with the highest degrees) to find key regulator (KR) genes. We found that two genes, CDK1 and HSP90AA1, were common in the analysis suggesting a significant regulatory role of CDK1 and HSP90AA1 in non-small cell lung cancer. Our study using a network theoretical approach, as a summary, suggests CDK1 and HSP90AA1 as key regulator genes in complex NSCLC network. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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17 pages, 2949 KiB

Open AccessArticle

High Expression of Interferon Pathway Genes CXCL10 and STAT2 Is Associated with Activated T-Cell Signature and Better Outcome of Oral Cancer Patients

by Yun-Cian Huang, Jau-Ling Huang, Lu-Chia Tseng, Ping-Hung Yu, Si-Yun Chen and Chang-Shen Lin

J. Pers. Med. 2022, 12(2), 140; https://doi.org/10.3390/jpm12020140 - 21 Jan 2022

Cited by 8 | Viewed by 3719

Abstract

To improve the survival rate of cancer patients, biomarkers for both early diagnosis and patient stratification for appropriate therapeutics play crucial roles in precision oncology. Investigation of altered gene expression and the relevant molecular pathways in cancer cells are helpful for discovering such [...] Read more.

To improve the survival rate of cancer patients, biomarkers for both early diagnosis and patient stratification for appropriate therapeutics play crucial roles in precision oncology. Investigation of altered gene expression and the relevant molecular pathways in cancer cells are helpful for discovering such biomarkers. In this study, we explore the potential prognostic biomarkers for oral cancer patients through systematically analyzing five oral cancer transcriptomic data sets (TCGA, GSE23558, GSE30784, GSE37991, and GSE138206). Gene Set Enrichment Analysis (GSEA) was individually applied to each data set and the upregulated Hallmark molecular pathways of each data set were intersected to generate 13 common pathways including interferon-α/γ pathways. Among the 5 oral cancer data sets, 43 interferon pathway genes were commonly upregulated and 17 genes exhibited prognostic values in TCGA cohort. After validating in another oral cancer cohort (GSE65858), high expressions of C-X-C motif chemokine ligand 10 (CXCL10) and Signal transducer and activator of transcription 2 (STAT2) were confirmed to be good prognostic biomarkers. GSEA of oral cancers stratified by CXCL10/STAT2 expression showed that activation of T-cell pathways and increased tumor infiltration scores of Type 1 T helper (Th1) and CD8+ T cells were associated with high CXCL10/STAT2 expression. These results suggest that high CXCL10/STAT2 expression can predict a favorable outcome in oral cancer patients. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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17 pages, 2873 KiB

Open AccessArticle

PharmVIP: A Web-Based Tool for Pharmacogenomic Variant Analysis and Interpretation

by Jittima Piriyapongsa, Chanathip Sukritha, Pavita Kaewprommal, Chalermpong Intarat, Kwankom Triparn, Krittin Phornsiricharoenphant, Chadapohn Chaosrikul, Philip J. Shaw, Wasun Chantratita, Surakameth Mahasirimongkol and Sissades Tongsima

J. Pers. Med. 2021, 11(11), 1230; https://doi.org/10.3390/jpm11111230 - 19 Nov 2021

Cited by 6 | Viewed by 4813

Abstract

The increasing availability of next generation sequencing (NGS) for personal genomics could promote pharmacogenomics (PGx) discovery and application. However, current tools for analysis and interpretation of pharmacogenomic variants from NGS data are inadequate, as none offer comprehensive analytic functions in a simple, web-based [...] Read more.

The increasing availability of next generation sequencing (NGS) for personal genomics could promote pharmacogenomics (PGx) discovery and application. However, current tools for analysis and interpretation of pharmacogenomic variants from NGS data are inadequate, as none offer comprehensive analytic functions in a simple, web-based platform. In addition, no tools exist to analyze human leukocyte antigen (HLA) genes for determining potential risks of immune-mediated adverse drug reaction (IM-ADR). We describe PharmVIP, a web-based PGx tool, for one-stop comprehensive analysis and interpretation of genome-wide variants obtained from NGS platforms. PharmVIP comprises three main interpretation modules covering analyses of pharmacogenes involved in pharmacokinetics, pharmacodynamics and IM-ADR. The Guideline module provides Clinical Pharmacogenetics Implementation Consortium (CPIC) drug guideline recommendations based on the translation of genotypic data in genes having guidelines. The HLA module reports HLA genotypes, potential adverse drug reactions, and the relevant drug guidelines. The Pharmacogenes module is employed for prioritizing variants according to variant effect on gene function. Detailed, customizable reports are provided as exportable files and as an interactive web version. PharmVIP is a new integrated NGS workflow for the PGx community to facilitate discovery and clinical application. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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13 pages, 4702 KiB

Open AccessArticle

LASSO and Bioinformatics Analysis in the Identification of Key Genes for Prognostic Genes of Gynecologic Cancer

by Shao-Hua Yu, Jia-Hua Cai, De-Lun Chen, Szu-Han Liao, Yi-Zhen Lin, Yu-Ting Chung, Jeffrey J. P. Tsai and Charles C. N. Wang

J. Pers. Med. 2021, 11(11), 1177; https://doi.org/10.3390/jpm11111177 - 11 Nov 2021

Cited by 18 | Viewed by 6276

Abstract

The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As [...] Read more.

The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As the underlying molecular mechanisms in both cervical and endometrial cancer remain unclear, a comprehensive and systematic bioinformatics analysis is required. In our study, gene expression profiles of GSE9750, GES7803, GES63514, GES17025, GES115810, and GES36389 downloaded from Gene Expression Omnibus (GEO) were utilized to analyze differential gene expression between cancer and normal tissues. A total of 78 differentially expressed genes (DEGs) common to CC and EC were identified to perform the functional enrichment analyses, including gene ontology and pathway analysis. KEGG pathway analysis of 78 DEGs indicated that three main types of pathway participate in the mechanism of gynecologic cancer such as drug metabolism, signal transduction, and tumorigenesis and development. Furthermore, 20 diagnostic signatures were confirmed using the least absolute shrink and selection operator (LASSO) regression with 10-fold cross validation. Finally, we used the GEPIA2 online tool to verify the expression of 20 genes selected by the LASSO regression model. Among them, the expression of PAMR1 and SLC24A3 in tumor tissues was downregulated significantly compared to the normal tissue, and found to be statistically significant in survival rates between the CC and EC of patients (p < 0.05). The two genes have their function: (1.) PAMR1 is a tumor suppressor gene, and many studies have proven that overexpression of the gene markedly suppresses cell growth, especially in breast cancer and polycystic ovary syndrome; (2.) SLC24A3 is a sodium–calcium regulator of cells, and high SLC24A3 levels are associated with poor prognosis. In our study, the gene signatures can be used to predict CC and EC prognosis, which could provide novel clinical evidence to serve as a potential biomarker for future diagnosis and treatment. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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22 pages, 9009 KiB

Open AccessArticle

Potential Prognostic Biomarkers of NIMA (Never in Mitosis, Gene A)-Related Kinase (NEK) Family Members in Breast Cancer

by Gangga Anuraga, Wei-Jan Wang, Nam Nhut Phan, Nu Thuy An Ton, Hoang Dang Khoa Ta, Fidelia Berenice Prayugo, Do Thi Minh Xuan, Su-Chi Ku, Yung-Fu Wu, Vivin Andriani, Muhammad Athoillah, Kuen-Haur Lee and Chih-Yang Wang

J. Pers. Med. 2021, 11(11), 1089; https://doi.org/10.3390/jpm11111089 - 26 Oct 2021

Cited by 49 | Viewed by 5064

Abstract

Breast cancer remains the most common malignant cancer in women, with a staggering incidence of two million cases annually worldwide; therefore, it is crucial to explore novel biomarkers to assess the diagnosis and prognosis of breast cancer patients. NIMA-related kinase (NEK) protein kinase [...] Read more.

Breast cancer remains the most common malignant cancer in women, with a staggering incidence of two million cases annually worldwide; therefore, it is crucial to explore novel biomarkers to assess the diagnosis and prognosis of breast cancer patients. NIMA-related kinase (NEK) protein kinase contains 11 family members named NEK1-NEK11, which were discovered from Aspergillus Nidulans; however, the role of NEK family genes for tumor development remains unclear and requires additional study. In the present study, we investigate the prognosis relationships of NEK family genes for breast cancer development, as well as the gene expression signature via the bioinformatics approach. The results of several integrative analyses revealed that most of the NEK family genes are overexpressed in breast cancer. Among these family genes, NEK2/6/8 overexpression had poor prognostic significance in distant metastasis-free survival (DMFS) in breast cancer patients. Meanwhile, NEK2/6 had the highest level of DNA methylation, and the functional enrichment analysis from MetaCore and Gene Set Enrichment Analysis (GSEA) suggested that NEK2 was associated with the cell cycle, G2M checkpoint, DNA repair, E2F, MYC, MTORC1, and interferon-related signaling. Moreover, Tumor Immune Estimation Resource (TIMER) results showed that the transcriptional levels of NEK2 were positively correlated with immune infiltration of B cells and CD4⁺ T Cell. Collectively, the current study indicated that NEK family genes, especially NEK2 which is involved in immune infiltration, and may serve as prognosis biomarkers for breast cancer progression. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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14 pages, 2952 KiB

Open AccessArticle

Molecular Classification Models for Triple Negative Breast Cancer Subtype Using Machine Learning

by Rassanee Bissanum, Sitthichok Chaichulee, Rawikant Kamolphiwong, Raphatphorn Navakanitworakul and Kanyanatt Kanokwiroon

J. Pers. Med. 2021, 11(9), 881; https://doi.org/10.3390/jpm11090881 - 1 Sep 2021

Cited by 14 | Viewed by 4073

Abstract

Triple negative breast cancer (TNBC) lacks well-defined molecular targets and is highly heterogenous, making treatment challenging. Using gene expression analysis, TNBC has been classified into four different subtypes: basal-like immune-activated (BLIA), basal-like immune-suppressed (BLIS), mesenchymal (MES), and luminal androgen receptor (LAR). However, there [...] Read more.

Triple negative breast cancer (TNBC) lacks well-defined molecular targets and is highly heterogenous, making treatment challenging. Using gene expression analysis, TNBC has been classified into four different subtypes: basal-like immune-activated (BLIA), basal-like immune-suppressed (BLIS), mesenchymal (MES), and luminal androgen receptor (LAR). However, there is currently no standardized method for classifying TNBC subtypes. We attempted to define a gene signature for each subtype, and to develop a classification method based on machine learning (ML) for TNBC subtyping. In these experiments, gene expression microarray data for TNBC patients were downloaded from the Gene Expression Omnibus database. Differentially expressed genes unique to 198 known TNBC cases were identified and selected as a training gene set to train in seven different classification models. We produced a training set consisting of 719 DEGs selected from uniquely expressed genes of all four subtypes. The highest average accuracy of classification of the BLIA, BLIS, MES, and LAR subtypes was achieved by the SVM algorithm (accuracy 95–98.8%; AUC 0.99–1.00). For model validation, we used 334 samples of unknown TNBC subtypes, of which 97 (29.04%), 73 (21.86%), 39 (11.68%) and 59 (17.66%) were predicted to be BLIA, BLIS, MES, and LAR, respectively. However, 66 TNBC samples (19.76%) could not be assigned to any subtype. These samples contained only three upregulated genes (EN1, PROM1, and CCL2). Each TNBC subtype had a unique gene expression pattern, which was confirmed by identification of DEGs and pathway analysis. These results indicated that our training gene set was suitable for development of classification models, and that the SVM algorithm could classify TNBC into four unique subtypes. Accurate and consistent classification of the TNBC subtypes is essential for personalized treatment and prognosis of TNBC. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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21 pages, 5938 KiB

Open AccessFeature PaperArticle

Multi-Omics Analysis of SOX4, SOX11, and SOX12 Expression and the Associated Pathways in Human Cancers

by Jaekwon Seok, Minchan Gil, Ahmed Abdal Dayem, Subbroto Kumar Saha and Ssang-Goo Cho

J. Pers. Med. 2021, 11(8), 823; https://doi.org/10.3390/jpm11080823 - 23 Aug 2021

Cited by 10 | Viewed by 3900

Abstract

The Sry-related HMG BOX (SOX) gene family encodes transcription factors containing highly conserved high-mobility group domains that bind to the minor groove in DNA. Although some SOX genes are known to be associated with tumorigenesis and cancer progression, their expression and prognostic value [...] Read more.

The Sry-related HMG BOX (SOX) gene family encodes transcription factors containing highly conserved high-mobility group domains that bind to the minor groove in DNA. Although some SOX genes are known to be associated with tumorigenesis and cancer progression, their expression and prognostic value have not been systematically studied. We performed multi-omic analysis to investigate the expression of SOX genes in human cancers. Expression and phylogenetic tree analyses of the SOX gene family revealed that the expression of three closely related SOX members, SOX4, SOX11, and SOX12, was increased in multiple cancers. Expression, mutation, and alteration of the three SOX members were evaluated using the Oncomine and cBioPortal databases, and the correlation between these genes and clinical outcomes in various cancers was examined using the Kaplan–Meier, PrognoScan, and R2 database analyses. The genes commonly correlated with the three SOX members were categorized in key pathways related to the cell cycle, mitosis, immune system, and cancer progression in liver cancer and sarcoma. Additionally, functional protein partners with three SOX proteins and their probable signaling pathways were explored using the STRING database. This study suggests the prognostic value of the expression of three SOX genes and their associated pathways in various human cancers. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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15 pages, 2226 KiB

Open AccessArticle

Body Mass Index and Birth Weight Improve Polygenic Risk Score for Type 2 Diabetes

by Avigail Moldovan, Yedael Y. Waldman, Nadav Brandes and Michal Linial

J. Pers. Med. 2021, 11(6), 582; https://doi.org/10.3390/jpm11060582 - 21 Jun 2021

Cited by 10 | Viewed by 5282

Abstract

One of the major challenges in the post-genomic era is elucidating the genetic basis of human diseases. In recent years, studies have shown that polygenic risk scores (PRS), based on aggregated information from millions of variants across the human genome, can [...] Read more.

One of the major challenges in the post-genomic era is elucidating the genetic basis of human diseases. In recent years, studies have shown that polygenic risk scores (PRS), based on aggregated information from millions of variants across the human genome, can estimate individual risk for common diseases. In practice, the current medical practice still predominantly relies on physiological and clinical indicators to assess personal disease risk. For example, caregivers mark individuals with high body mass index (BMI) as having an increased risk to develop type 2 diabetes (T2D). An important question is whether combining PRS with clinical metrics can increase the power of disease prediction in particular from early life. In this work we examined this question, focusing on T2D. We present here a sex-specific integrated approach that combines PRS with additional measurements and age to define a new risk score. We show that such approach combining adult BMI and PRS achieves considerably better prediction than each of the measures on unrelated Caucasians in the UK Biobank (UKB, n = 290,584). Likewise, integrating PRS with self-reports on birth weight (n = 172,239) and comparative body size at age ten (n = 287,203) also substantially enhance prediction as compared to each of its components. While the integration of PRS with BMI achieved better results as compared to the other measurements, the latter are early-life measurements that can be integrated already at childhood, to allow preemptive intervention for those at high risk to develop T2D. Our integrated approach can be easily generalized to other diseases, with the relevant early-life measurements. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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25 pages, 9170 KiB

Open AccessArticle

Accurate Segmentation of Nuclear Regions with Multi-Organ Histopathology Images Using Artificial Intelligence for Cancer Diagnosis in Personalized Medicine

by Tahir Mahmood, Muhammad Owais, Kyoung Jun Noh, Hyo Sik Yoon, Ja Hyung Koo, Adnan Haider, Haseeb Sultan and Kang Ryoung Park

J. Pers. Med. 2021, 11(6), 515; https://doi.org/10.3390/jpm11060515 - 4 Jun 2021

Cited by 26 | Viewed by 6205

Abstract

Accurate nuclear segmentation in histopathology images plays a key role in digital pathology. It is considered a prerequisite for the determination of cell phenotype, nuclear morphometrics, cell classification, and the grading and prognosis of cancer. However, it is a very challenging task because [...] Read more.

Accurate nuclear segmentation in histopathology images plays a key role in digital pathology. It is considered a prerequisite for the determination of cell phenotype, nuclear morphometrics, cell classification, and the grading and prognosis of cancer. However, it is a very challenging task because of the different types of nuclei, large intraclass variations, and diverse cell morphologies. Consequently, the manual inspection of such images under high-resolution microscopes is tedious and time-consuming. Alternatively, artificial intelligence (AI)-based automated techniques, which are fast and robust, and require less human effort, can be used. Recently, several AI-based nuclear segmentation techniques have been proposed. They have shown a significant performance improvement for this task, but there is room for further improvement. Thus, we propose an AI-based nuclear segmentation technique in which we adopt a new nuclear segmentation network empowered by residual skip connections to address this issue. Experiments were performed on two publicly available datasets: (1) The Cancer Genome Atlas (TCGA), and (2) Triple-Negative Breast Cancer (TNBC). The results show that our proposed technique achieves an aggregated Jaccard index (AJI) of 0.6794, Dice coefficient of 0.8084, and F1-measure of 0.8547 on TCGA dataset, and an AJI of 0.7332, Dice coefficient of 0.8441, precision of 0.8352, recall of 0.8306, and F1-measure of 0.8329 on the TNBC dataset. These values are higher than those of the state-of-the-art methods. Full article

(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)

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