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2023 International Conference on Informatics, Multimedia, Cyber and Information Systems, ICIMCIS 2023

作者： Nirwantono, Rudi Assidqi, Khoirunnisa Hidayat, Alam Ahmad Pebrianto Trinugroho, Joko Pardamean, Bens Bina Nusantara University Faculty of Engineering Bioinformatics and Data Science Research Center Biotechnology Department Jakarta11480 Indonesia Bina Nusantara University Faculty of Engineering Food Biotechnology Research Center Biotechnology Department Jakarta11480 Indonesia Bina Nusantara University School of Computer Science Bioinformatics and Data Science Research Center Mathematics Departement Jakarta11480 Indonesia Bina Nusantara University Bioinformatics and Data Science Research Center Jakarta11480 Indonesia Bina Nusantara University Binus Graduate Program - Computer Science Program Computer Science Department Jakarta11480 Indonesia

ISBN: (纸本)9798350307306

The infection of Plasmodium vivax is relatively less virulent than the deathliest Plasmodium falciparum. However, it still can lead to a fatal case and often induces recurring malaria due to dormant parasites in the liver. Thus, the research to study the drug to treat Plasmodium vivax is essential, where the enzyme dihydroorotate dehydrogenase (DHODH) has recently become a new drug target. However, the drug-enzyme interaction study has only recently been conducted in Plasmodium falciparum (pfDHODH) due to the lack of the 3D structure of enzyme DHODH from Plasmodium vivax that is crucial for the study. Therefore, this study aimed to perform the modelling study of Plasmodium vivax DHODH (PvDHODH) to create a 3D structure as a basis for drug-protein interaction study in upcoming studies. Sequence pvDHODH (Accession: SCO68359.1) was used in homology modelling using Modeller 10.2 with the crystal structure of DHODH from DHODH (Accession: 7KZY) as a template. Overall, the model generated from the homology modelling was considered a good model, and the 3D structure was close to the native state according to several parameters, including DOPE score, GA341 score, QMEAN4 value, 3D-1D score, ERRAT2 score, and ProSA score. Ramachandran plot also revealed that almost all amino acids were distributed in the desirable and allowed area (99.1%), and only 0.9% were in generously allowed regions. Superimposition of the model with the template also indicated that the model has an almost similar structure and amino acids positioning, including in the binding pocket and active site. Therefore, the model can be used for downstream analysis in drug-protein interaction studies. Nevertheless, some improvements can still be performed to upgrade the quality of the model by deleting unaligned residues on the C-terminal and realigning the residues at the doubting site. © 2023 IEEE.

关键词： Amino acids

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Lymphatic endothelial mTORC1 instructs metabolic and developmental signaling during lymphangiogenesis

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Developmental Cell 2025年

作者： Han, Fei Simeroth, Summer Zhu, Jie Gryniuk, Irma Pranay, Atul Chen, Weiqing Wang, Yuan Cai, Yuanyuan Shen, Zhiyuan Wang, Guangyu Griffin, Courtney T. Xia, Lijun Yu, Pengchun Cardiovascular Biology Research Program Oklahoma Medical Research Foundation Oklahoma City 73104 OK United States Department of Cell Biology University of Oklahoma Health Sciences Center Oklahoma City 73104 OK United States Aging and Metabolism Research Program Oklahoma Medical Research Foundation Oklahoma City 73104 OK United States Center for Bioinformatics and Computational Biology Houston Methodist Research Institute Houston TX United States Department of Physiology Biophysics & Systems Biology Weill Cornell Graduate School of Medical Science Weill Cornell Medicine Cornell University New York NY United States Department of Radiation Oncology Rutgers Cancer Institute and Robert Wood Johnson Medical School Rutgers University New Brunswick NJ United States Center for Cardiovascular Regeneration Houston Methodist Research Institute Houston TX United States Center for RNA Therapeutics Houston Methodist Research Institute Houston TX United States Department of Cardiothoracic Surgery Weill Cornell Medicine Cornell University New York NY United States Department of Biochemistry and Physiology University of Oklahoma Health Sciences Center Oklahoma City OK United States

The lymphatic vasculature comprises lymphatic capillaries and collecting vessels. To support lymphatic development, lymphatic endothelial cells (LECs) utilize nutrients to fuel lymphangiogenic processes. Meanwhile, LECs maintain constant prospero homeobox 1 (PROX1) expression critical for lymphatic specification. However, molecular mechanisms orchestrating nutrient metabolism while sustaining PROX1 levels in LECs remain unclear. Here, we show that loss of RAPTOR, an indispensable mechanistic target of rapamycin complex 1 (mTORC1) component, downregulates PROX1 and impairs lymphatic capillary growth and differentiation of collecting lymphatics in mice. Mechanistically, mTORC1 inhibition in mouse and human LECs causes Myc reduction, which decreases hexokinase 2 (HK2) and glutaminase (GLS), inhibiting glycolysis and glutaminolysis. Myc or HK2/GLS ablation impedes lymphatic capillary and collecting vessel formation. Interestingly, mTORC1 regulation of PROX1 is independent of Myc-HK2/GLS signaling. Moreover, genetic interaction analysis indicates that Myc and PROX1 play crucial roles in mTORC1-regulated lymphatic development. Collectively, our findings identify mTORC1 as a key regulator of metabolic programs and PROX1 expression during lymphangiogenesis. © 2025 Elsevier Inc.

关键词： glutaminase glutaminolysis glycolysis hexokinase 2 lymphangiogenesis lymphatic endothelial cell lymphatic vessel mTORC1 Myc PROX1

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Large-scale analysis of human heavy chain V(D)J recombination patterns

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Immunome Research 2008年第1期4卷 1-10页

作者： Volpe, Joseph M Kepler, Thomas B Center for Computational Immunology Duke University Durham NC United States Department of Immunology Duke Univeristy Medical Center Durham NC United States Department of Biostatistics and Bioinformatics Duke Univeristy Medical Center Durham NC United States Institute of Statistics and Decision Sciences Duke Univeristy Durham NC United States Computational Biology and Bioinformatics Graduate Program Institute for Genome Sciences and Policy Duke Univeristy Durham NC United States

Background. The processes involved in the somatic assembly of antigen receptor genes are unique to the immune system and are driven largely by random events. Subtle biases, however, may exist and provide clues to the molecular mechanisms involved in their assembly and selection. Large-scale efforts to provide baseline data about the genetic characteristics of immunoglobulin (Ig) genes and the mechanisms involved in their assembly have recently become possible due to the rapid growth of genetic databases. Results. We gathered and analyzed nearly 6,500 productive human Ig heavy chain genes and compared them with 325 non-productive Ig genes that were originally rearranged out of frame and therefore incapable of being biased by selection. We found evidence for differences in n-nucleotide tract length distributions which have interesting interpretations for the mechanisms involved in n-nucleotide polymerization. Additionally, we found striking statistical evidence for pairing preferences among D and J segments. We present a statistical model to support our hypothesis that these pairing biases are due to multiple sequential D-to-J rearrangements. Conclusion. We present here the most precise estimates of gene segment usage frequencies currently available along with analyses regarding n-nucleotide distributions and D-J segment pair preferences. Additionally, we provide the first statistical evidence that sequential D-J recombinations occur at the human heavy chain locus during B-cell ontogeny with an approximate frequency of 20%.

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Database Design for Indonesian Scholarship Recommender Systems 7

Database Design for Indonesian Scholarship Recommender Syste...

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7th International Conference on Information Management and Technology, ICIMTech 2022

作者： Elwirehardja, Gregorius Natanael Jason Dominic, Nicholas Pardamean, Bens BINUS Graduate Program - Master of Computer Science Bina Nusantara University Computer Science Department Jakarta11480 Indonesia Bioinformatics and Data Science Research Center Bina Nusantara University Jakarta11480 Indonesia

ISBN: (数字)9781665450904

ISBN: (纸本)9781665450904

Following the evolution of technology, researchers have conducted several studies to propose reliable scholarship recommender systems. However, few have explored the data storage systems, which are highly beneficial to collect huge volumes of real data in training the recommender systems. In this paper, a database design for collecting such data was proposed, equipped with integer encodings for categorical variables and a method to normalize variables with varying ranges. Using Connoly and Begg's database design method, the final design consisted of a normalized Entity Relationship Diagram (ERD) and data dictionaries. The design was also constructed to support usages of various data for determining scholarship recipients, including education history, achievements, and organizational experiences. The proposed design can be implemented on information systems to allow easier information access for scholarships in Indonesia. © 2022 IEEE.

关键词： Recommender systems

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Knowledge Graph-Enhanced Semantic Cache for Low-Latency and Cost-Effective Inference in Large Language Models 9

Knowledge Graph-Enhanced Semantic Cache for Low-Latency and ...

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9th International Conference on Information Management and Technology, ICIMTech 2024

作者： Dominic, Nicholas Pardamean, Bens Bina Nusantara University Bioinformatics & Data Science Research Center Jakarta11480 Indonesia BINUS Graduate Program - Master of Computer Science Bina Nusantara University Computer Science Department Jakarta11480 Indonesia

ISBN: (纸本)9798350390025

In organizational knowledge management, Large Language Model (LLM) caches act as a semantic repository gathered from previous LLM responses. Due to intensive calls from multiple users, LLM may suffer from high inference latency. While there are many prior available approaches to solve this problem, most of them are inherently complex. This paper introduced a Knowledge Graph-enhanced Semantic Cache mechanism as an alternative, lightweight technique to boost retrieval for similar prompts. The latest state-of-the-art open-source LLM, named Google's Gemma-2B-it, was used to generate sample prompts and responses as a draft, while a knowledge graph (KG) was built from Wikipedia sentences. To create embeddings of prompts and KG, all-MiniLM-L6-v2 from SentenceTransformer was used. This new cache system resulted in up to 28% improvement over a standard model. In particular, reinforcement with KG cache embeddings yielded more than 85% semantic cache accuracy. To map the next trajectory of this pilot study, an overview of the extended framework for LLM knowledge management was also presented in this paper. The framework includes the new KG- enhanced cache system equipped with scalable security and fallback mechanisms that can promote green technology through substantial improvements in latency, throughput, and overall LLM costs. © 2024 IEEE.

关键词： Knowledge graph

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Exploring Recurrent Neural Network Models for Depression Detection Through Facial Expressions: A Systematic Literature Review 6

Exploring Recurrent Neural Network Models for Depression Det...

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6th International Conference on Computer and Informatics Engineering, IC2IE 2023

作者： Rumahorbo, Brilyan Nathanael Pardamean, Bens Elwirehardja, Gregorius Natanael Bina Nusantara University Binus Graduate Program - Master of Computer Science Computer Science Department Jakarta11480 Indonesia Bina Nusantara University Bioinformatics and Data Science Research Center Jakarta11480 Indonesia

ISBN: (纸本)9798350345162

Major Depressive Disorder (MDD) is a prevalent mental disorder, affecting a significant number of individuals, with estimates reaching 300 million cases worldwide. Currently, the diagnosis of this condition relies heavily on subjective assessments based on the experience of medical professionals. Therefore, researchers have turned to deep learning models to explore the detection of depression. The objective of this review is to gather information on detecting depression based on facial expressions in videos using deep learning techniques. Overall, this research found that RNN models achieved 7.22 MAE for AVEC2014. LSTM models produced 4.83 MAE for DAIC-WOZ, while GRU models achieved an accuracy of 89.77% for DAIC-WOZ. Features like Facial Action Units (FAU), eye gaze, and landmarks show great potential and need to be further analyzed to improve results. Analysis can include applying feature engineering techniques. Aggregation methods, such as mean calculation, are recommended as effective approaches for data processing. This Systematic Literature Review found that facial expressions do have relevant patterns related to MDD. © 2023 IEEE.

关键词： deep learning facial expression GRU LSTM major depressive disorder

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Web Information System Design for Fast Protein Post-Translational Modification Site Prediction 7

Web Information System Design for Fast Protein Post-Translat...

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7th International Conference on Information Management and Technology, ICIMTech 2022

作者： Elwirehardja, Gregorius Natanael Dominic, Nicholas Pardamean, Bens BINUS Graduate Program - Master of Computer Science Bina Nusantara University Computer Science Department Jakarta11480 Indonesia Research Center Bina Nusantara University Bioinformatics and Data Science Jakarta11480 Indonesia

ISBN: (数字)9781665450904

ISBN: (纸本)9781665450904

In the field of bioinformatics, the protein Post-Translational Modification (PTM) site prediction has been widely studied and Web Information Systems (WIS) has been deployed by researchers for this task. Through a literature review and benchmarking process, we identified the requirements which included quick predictions, efficient memory usage, and input validations. However, no detailed designs have been proposed so far, which may have contributed to some requirements not being implemented in some of the websites. Therefore, we propose a detailed WIS conceptual design, which can be used for predicting the sites of multiple PTM types, equipped with a validation algorithm and compared the usage of various string searching algorithms as well as file storage formats. Experiment results showed that the linear search algorithm is the fastest for this task and storing the protein data in npz format when performing multi-PTMs site prediction can assist in reducing memory usage. The proposed design can be implemented into user-friendly web tools that are both efficient in speed and memory usage in future studies. © 2022 IEEE.

关键词： Forecasting

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A zinc finger-dependent, PRDM13-driven mechanism regulates retinal progenitor cell fate from mouse embryonic stem cells via WNT signaling

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Stem cell reports 2025年 102508页

作者： Brian W Basinski Yuanhao Huang Qiang Li Charukesi D Sivakumar Tyler J Carman Hana M Pan Jing Xu D Ford Hannum Jie Liu Rajesh C Rao Department of Ophthalmology and Visual Science W.K. Kellogg Eye Center University of Michigan Ann Arbor MI 48105 USA Molecular and Cellular Pathology Graduate Program Department of Pathology University of Michigan Ann Arbor MI 48105 USA. Department of Computational Medicine and Bioinformatics Ann Arbor MI 48105 USA. Department of Ophthalmology and Visual Science W.K. Kellogg Eye Center University of Michigan Ann Arbor MI 48105 USA. Molecular and Cellular Pathology Graduate Program Department of Pathology University of Michigan Ann Arbor MI 48105 USA Department of Computational Medicine and Bioinformatics Ann Arbor MI 48105 USA Department of Human Genetics University of Michigan Ann Arbor MI 48105 USA Rogel Cancer Center University of Michigan Ann Arbor MI 48105 USA Center of Computational Medicine and Bioinformatics University of Michigan Ann Arbor MI 48105 USA Center for RNA Biomedicine University of Michigan Ann Arbor MI 48105 USA A. Alfred Taubman Medical Research Institute University of Michigan Ann Arbor MI 48105 USA Section of Ophthalmology Surgical Service Veterans Administration Ann Arbor Healthcare System Ann Arbor MI 48105 USA. Electronic address: rajeshr@umich.edu.

The transcriptional regulation underlying eye field (retinal primordium) development requires precise control, yet the mechanisms guiding lineage-specific differentiation within the central nervous system (CNS) remain incompletely understood. Using neuroectoderm (NE) organoids derived from mouse embryonic stem cells, we investigate the role of PRDM13 in eye field specification. We demonstrate that Prdm13 expression inhibits RX eye field fate but permits non-eye field NE differentiation, an effect that depends on its first and second zinc-finger domains. Prdm13 activates the WNT/β-catenin signaling pathway during differentiation, leading to downregulation of key transcription factors crucial for establishing the eye field. Pharmacological inhibition of WNT signaling abolishes PRDM13-mediated suppression, restoring RX eye field differentiation. Our work reveals a previously undescribed PRDM13-WNT signaling axis that regulates lineage-specific neural differentiation of embryonic stem cells.

关键词： PRDM13 WNT organoids retinal development stem cells

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Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development

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Nature Neuroscience 2025年 1-14页

作者： Ya’el Courtney Joshua P. Head Neil Dani Frederick B. Shipley Maria K. Lehtinen Olga V. Chechneva Cameron Sadegh Yong Zhang Michael J. Holtzman Towia A. Libermann Department of Pathology Boston Children’s Hospital and Harvard Medical School Boston MA USA Graduate Program in Neuroscience Harvard Medical School Boston MA USA Department of Cell and Developmental Biology Vanderbilt University Nashville TN USA Graduate Program in Biophysics Harvard University Cambridge MA USA Department of Neurosurgery University of California Davis Sacramento CA USA Pulmonary and Critical Care Medicine Department of Medicine Washington University School of Medicine St. Louis MO USA Proteomics Bioinformatics and Systems Biology Center Beth Israel Deaconess Medical Center and Harvard Medical School Boston MA USA

The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development; yet, embryonic ChP secretory mechanisms remain poorly defined. Here we identify apocrine secretion by embryonic ChP epithelial cells as a key regulator of the CSF proteome and neurodevelopment in male and female mice. We demonstrate that the activation of serotonergic 5-HT2Creceptors (by WAY-161503) triggers sustained Ca2+signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors lining the brain’s ventricles and shifting their developmental trajectory. Inducing ChP secretion in utero in mice disrupts neural progenitor dynamics, cerebral cortical architecture and offspring behavior. Additionally, illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in the mouse embryo. Our findings reveal a fundamental secretory pathway in the ChP that shapes brain development, highlighting how its disruption can have lasting consequences for brain health.

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Characterizing Mutually Exclusive Driver Mutations in Pan-Cancer

Characterizing Mutually Exclusive Driver Mutations in Pan-Ca...

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IEEE International Conference on bioinformatics and Biomedicine (BIBM)

作者： Yifan Zhang William Yang Jun S. Liu Mary Qu Yang MidSouth Bioinformatics Center and Bioinformatics Program University of Arkansas at Little Rock Univ. of Arkansas Medical Sciences Little Rock USA Carnegie Mellon University School of Computer Science Pittsburgh USA Harvard University Cambridge USA

ISBN: (纸本)9781728118680

Efforts on cancer genomic study have revealed that mutations in cancer-driving oncogenes tend to mutually exclusive. To understand this tumorigenic mechanism and common cancer features, large-scale genomic study and molecular analyses across many cancer types are essential. We compiled somatic mutation and transcriptome profiles for a pan-cancer dataset that contains tumor tissue samples from 32 cancer types for over 10,000 patients. The genomic and molecular analysis was applied to four pan-cancer subgroups including pan-gastrointestinal, pan-gynecological, pan-kidney and pan-squamous, as well as the entire patient group. We identified seven genes, TP53, PIK3CA, PTEN, PIK3R1, LRP1B, CDH1, and TRRAP exhibited mutually exclusive mutation patterns across all cancer types (adjusted ). The mutations in these genes occurred in 55.9% of all cancer patients and over 70% of patients with pan-gastrointestinal, pan-gynecological and pan-squamous. Excepting LRP1B, the other six genes are included in the known cancer pathways. Notably, TP53, PIK3CA, and PIK3R1 are involved in over 20 cancer-related pathways. The co-expression network analysis suggested that LRP1B was associated with multiple genes that showed significant enrichment in Wnt signal pathway (adjusted p=0.0023) and ERBB signal pathway (adjusted p=0.0097). We further constructed a regulatory network to infer novel regulations of LRP1B in cancer. In addition, based on the mutations in the seven genes, we divided the patients into different groups for survival analysis. We found that the survival rate of the patient group with TP53 mutations was significantly shorter than in other groups (log rank p = 5.88e-10) in pan-gynecological. Our analysis systematically revealed the mutually exclusive mutation patterns of seven cancer genes across 32 cancer types. It helps us to better understanding the relations among different cancer types and pan-cancer subgroups, providing new insights into common mechanisms underlying diver

关键词： cancer cellular biophysics genetics genomics gynaecology kidney molecular biophysics tumours LRP1B gene cellular biophysics molecular biology Gynecology Genomics Mutually exclusive Tumours PIK3R1 gene Genetics Mutation Kidney Oncogenes

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