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    Prognostic Biomarker Selection for Breast Cancer using Bioinformatics and Deep Learning

    , M.Sc. Thesis Sharif University of Technology Salimi , Adel (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    Triple Negative Breast Cancer (TNBC) is an invasive subtype of breast cancer. Finding prognostic biomarkers is helpful in choosing the appropriate treatment procedure for patients of this cancer. In recent years, the role of microRNAs in various biological processes, including cancer, has been identified, and their accessibility and stability have made these types of molecules an ideal biomarker. In the first phase of this study, with the aim of overcoming the limitations of previous studies, a new bioinformatics protocol has been proposed to investigate the prognostic miRNAs of triple negative breast cancer. First, using survival analysis, 56 prognostic miRNAs which had a significant... 

    Unsupervised Neuronal Spike Sorting by Deep Learning Methods

    , M.Sc. Thesis Sharif University of Technology Rahmani, Saeed (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    Unsupervised neural spike sorting is a crucial tool in studying neural systems in the resolution of a neural cell. In extracellular recording from neural cells, the voltage of media is captured by the electrodes. The situation is possible that an electrode record activity of multiple neurons at the same time. The spike sorting goal is assigning each spike (extracellular recorded neural action potential) to a neural cell that generates it. Conventionally, more than one electrode is used to recording media voltages. The electrodes are placed in a small space as a single device called a multi-electrode array. After the spike sorting procedure, the occurrence time of activity of several cells is... 

    Cancer Detection Classification by cfDNA Methylation

    , M.Sc. Thesis Sharif University of Technology Ezzati, Saeedeh (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    Traditional techniques use invasive histology techniques to diagnose cancer. Cancer tissue is sampled directly in this method, which is very painful for the patient. In recent years, scientists have discovered that the cell world is released into the blood plasma after cell death, obtaining useful cancer information. Since methylation changes in cancer cells are very significant and the death rate of cancer cells is high, the methylation of each tissue is different from the other. Furthermore, they were diagnosing the type of cancer.On the other hand, due to the different patterns in methylated DNA with normal DNA and the use of bisulfite treatment technique to detect the degree of... 

    Multi-omic Single-cell Data Integration Using Deep Neural Networks

    , M.Sc. Thesis Sharif University of Technology Omidi, Alireza (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    The advent and advance of single-cell technologies have enabled us to measure the cell function and identity by using different assays and viewing it by different technologies. Nowadays, we are able to measure multiple feature vectors from same- single cells from multiple abstract molecular levels (genome, transcriptome, proteome, ...) simultaneously. Hence, the analysts can view the cell from different yet correlated angles and study their behaviours. Such progress in joint single-cell assessments plus the development and spread of more common single-cell assays - that measure one feature vector per cell - caused the growing need for computational tools to integrate these datasets in order... 

    Developing Active Learning Methods to Improve Classification of Medical Images

    , M.Sc. Thesis Sharif University of Technology Najafi, Mostafa (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    With the growing use of machine learning algorithms, especially in deep neural networks, the need for annotated data for supervised learning has also increased. In many cases, it is possible to collect data widely, but annotating all of these data is usually very time-consuming, expensive, and even impossible in some cases. The goal of active learning algorithms is to maximize the model’s performance with the least annotated data. Active learning algorithms are iterative algorithms that train the model in each iteration with the current annotated data. Then, using the results of the model on the remaining data without annotation, select some new data to annotate. This process usually... 

    Improving Peptide-MHC Class I Binding Prediction using Cross-Encoder Transformer Models

    , M.Sc. Thesis Sharif University of Technology Bahrami, Amirhossein (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    The Major Histocompatibility Complex (MHC) Class I molecules play a crucial role in the immune system. These molecules present peptides derived from intracellular proteins on the cell surface to be recognized by T cells. This process is vital for identifying and eliminating cancerous or infected cells. In cancer therapy, particularly in the development of personalized vaccines, accurately selecting peptides that can effectively bind to MHC Class I and stimulate a strong immune response is a significant challenge. This research introduces an innovative neural network model that utilizes a cross-encoder architecture and leverages a pre-trained model to simultaneously process peptide and MHC... 

    Analysis of DNA Methylation in Single-cell Resolution Using Algorithmic Methods and Deep Neural Networks

    , M.Sc. Thesis Sharif University of Technology Rasti Ghamsari, Ozra (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    DNA methylation in one of the most important epigenetic variations, which causes significant variations in gene expressions of mammalians. Our current knowledge about DNA methylation is based on measurments from samples of bulk data which cause ambiguity in intracellular differences and analysis of rare cell samples. For this reason, the ability to measure DNA methylation in single-cells has the potential to play an important role in understanding many biological processes including embryonic developement, disease progression including cancer, aging, chromosome instability, X chromosome inactivation, cell differentiation and genes regulation. Recent technological advances have enabled... 

    Prediction of HLA-Peptide Binding using 3D Structural Features

    , M.Sc. Thesis Sharif University of Technology Bagh Golshani, Marjan (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    The human leukocyte antigen protein, commonly known as HLA, has the ability to present small protein fragments called peptides on the surface of cells, whether they originate from within the cell or externally. The binding of these peptides to HLA receptors is a crucial step that triggers an immune response. By estimating the affinity between peptides and HLA class I, we can identify novel antigens that have the potential to be targeted by cancer therapeutic vaccines. Computational methods that predict the binding affinity between peptides and HLA receptors have the potential to expedite the design process of cancer vaccines. Currently, most computational methods exclusively rely on... 

    Binding Affinity Prediction Between Antibody and Antigen using Self-Supervised Learning

    , M.Sc. Thesis Sharif University of Technology Alikhani Ziaratgahi, Mohammad Hassan (Author) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    In recent years, monoclonal antibodies have gained attention as highly effective drugs for treating diseases, especially cancer. The high binding affinity between an antibody and its corresponding antigen is one of the key factors in triggering an effective immune response. Modeling binding affinity using machine learning is considered a promising and cost-effective computational approach; however, due to the lack of training data, the performance of these models is often poor and limited. In contrast, recent advances in geometric learning have demonstrated that incorporating the three-dimensional geometry of protein structures in the learning process can significantly impact 3D... 

    Machine Learning Approaches for the Prediction of Pathogenicity in Genome Variations

    , M.Sc. Thesis Sharif University of Technology Sahebi, Alireza (Author) ; Sharifi Zarchi, Ali (Supervisor) ; Asgari, Ehsannedin (Supervisor)
    Abstract
    Genome mutations whose effects are not specified pose one of the challenges in identifying genetic diseases. Utilizing wet lab tests to detect the pathogenicity of variants can be time-consuming and fiscally expensive. A rapid and cost-effective solution to this problem is the use of machine learning-based variant effect predictors, which have the ability to determine whether a mutation is pathogenic or not. The objective of this research is to predict the pathogenicity of genome variations. The proposed model exclusively utilizes the protein sequence as its input feature and does not have access to other protein features. The data used to construct the model comprises mutations with... 

    Quantification of in Vitro Drug Effects on COVID-19 through Analysis of Cellular Morphological Features

    , M.Sc. Thesis Sharif University of Technology Mirzaie, Nahal (Author) ; Rohban, Mohammad Hossein (Supervisor) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    The epidemic of Covid 19 has killed millions of people worldwide. Despite the efforts of scientists around the world, there is still no cure for this disease. Approval of newly designed drugs due to clinical trial periods is time-consuming and costly. For this reason, in the current emergency situation, it is important to have a solution for screening available approved drugs in order to find effective substances for this disease.High-throughput assays are a good option for such problems. In this field of research, image-based high-throughput assays are amongst the most effective and cost-effective methods that help quantify the response of treated cells by measuring cell... 

    Analyzing Cancer Cell Identity and Appropriative Subnetworks using Machine Learning

    , M.Sc. Thesis Sharif University of Technology Saberi, Ali (Author) ; Rabiee, Hamid Reza (Supervisor) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    From a long time ago cancer has been threatening human’s health, and researchers have been grappling with the phenomenon for numerous years. In the annals of this struggle, the number of cancer victims has outnumbered the survivals in a way that,until recently, suffering from cancer was perceived to be equivalent to death. Permanent defeat against cancer stems from the incomplete recognition of the phenomenon. In recent years, with the advent of technologies to extract information from the heart of cells and at the genome and transcriptome levels, man has been able to acquire a deeper understanding of cancer, its behavior and operation. Now that cancer is regarded to be a genetic disease,... 

    FAME: fast and memory efficient multiple sequences alignment tool through compatible chain of roots

    , Article Bioinformatics ; Volume 36, Issue 12 , 15 June , 2020 , Pages 3662-3668 Etminan, N ; Parvinnia, E ; Sharifi Zarchi, A ; Sharif University of Technology
    Oxford University Press  2020
    Abstract
    Motivation: Multiple sequence alignment (MSA) is important and challenging problem of computational biology. Most of the existing methods can only provide a short length multiple alignments in an acceptable time. Nevertheless, when the researchers confront the genome size in the multiple alignments, the process has required a huge processing space/time. Accordingly, using the method that can align genome size rapidly and precisely has a great effect, especially on the analysis of the very long alignments. Herein, we have proposed an efficient method, called FAME, which vertically divides sequences from the places that they have common areas; then they are arranged in consecutive order. Then... 

    A new multiple dna and protein sequences alignment method based on evolutionary algorithms

    , Article Journal of Knowledge and Health in Basic Medical Sciences ; Volume 16, Issue 1 , 2021 , Pages 13-20 ; 1735577X (ISSN) Etminan, N ; Parvinnia, E ; Sharifi Zarchi, A ; Sharif University of Technology
    Shahroud University of Medical Sciences  2021
    Abstract
    Introduction: The study of life and the detection of gene functions is an important issue in biological science. Multiple sequences alignment methods measure the similarity of DNA sequences. Nonetheless, when the size of genome sequences is increased, we encounter with the lack of memory and increasing the run time. Therefore, a fast method with a suitable accuracy for genome alignment has a significant impact on the analysis of long sequences. Methods: We introduce a new method in which, it first divides each sequence into short sequences. Then, it uses evolutionary algorithms to align the sequences. Results: The proposed method has been evaluated in seven datasets with different number of... 

    InterOpt: improved gene expression quantification in qPCR experiments using weighted aggregation of reference genes

    , Article iScience ; Volume 26, Issue 10 , 2023 ; 25890042 (ISSN) Salimi, A ; Rahmani, S ; Sharifi Zarchi, A ; Sharif University of Technology
    Elsevier Inc  2023
    Abstract
    qPCR is still the gold standard for gene expression quantification. However, its accuracy is highly dependent on the normalization procedure. The conventional method involves using the geometric mean of multiple study-specific reference genes (RGs) expression for cross-sample normalization. While research on selecting stably expressed RGs is extensive, scant literature exists regarding the optimal approach for aggregating multiple RGs into a unified RG. In this paper, we introduce a family of scale-invariant functions as an alternative to the geometric mean aggregation. Our candidate method (weighted geometric mean minimizing standard deviation) demonstrated significantly better results... 

    Cancer Detection and Classification in Histopathology Images Under Small Training Set

    , M.Sc. Thesis Sharif University of Technology Askari Farsangi, Amir Hossein (Author) ; Rohban, Mohammad Hossein (Supervisor) ; Sharifi Zarchi, Ali (Supervisor)
    Abstract
    Histopathology images are a type of medical images that are used to diagnose a variety of diseases. One of these illnesses is the Leukemia cancer, which has four different subtypes and is diagnosed using a blood smear image. As a result of the advancement of deep learning tools, models for diagnosing various types of disease from images have been developed in recent years.In this project, one of the best models developed to diagnose four different types of disease was replicated, and it was demonstrated that, while this model achieves acceptable accuracy, its decision is not based on medically significant criteria. In the following, a general method for diagnosing the disease is proposed... 

    DeePathology: Deep multi-task learning for inferring molecular pathology from cancer transcriptome

    , Article Scientific Reports ; Volume 9, Issue 1 , 2019 ; 20452322 (ISSN) Azarkhalili, B ; Saberi, A ; Chitsaz, H ; Sharifi Zarchi, A ; Sharif University of Technology
    Nature Publishing Group  2019
    Abstract
    Despite great advances, molecular cancer pathology is often limited to the use of a small number of biomarkers rather than the whole transcriptome, partly due to computational challenges. Here, we introduce a novel architecture of Deep Neural Networks (DNNs) that is capable of simultaneous inference of various properties of biological samples, through multi-task and transfer learning. It encodes the whole transcription profile into a strikingly low-dimensional latent vector of size 8, and then recovers mRNA and miRNA expression profiles, tissue and disease type from this vector. This latent space is significantly better than the original gene expression profiles for discriminating samples... 

    The assessment of efficient representation of drug features using deep learning for drug repositioning

    , Article BMC Bioinformatics ; Volume 20, Issue 1 , 2019 ; 14712105 (ISSN) Moridi, M ; Ghadirinia, M ; Sharifi Zarchi, A ; Zare Mirakabad, F ; Sharif University of Technology
    BioMed Central Ltd  2019
    Abstract
    Background: De novo drug discovery is a time-consuming and expensive process. Nowadays, drug repositioning is utilized as a common strategy to discover a new drug indication for existing drugs. This strategy is mostly used in cases with a limited number of candidate pairs of drugs and diseases. In other words, they are not scalable to a large number of drugs and diseases. Most of the in-silico methods mainly focus on linear approaches while non-linear models are still scarce for new indication predictions. Therefore, applying non-linear computational approaches can offer an opportunity to predict possible drug repositioning candidates. Results: In this study, we present a non-linear method... 

    The metabolic network model of primed/naive human embryonic stem cells underlines the importance of oxidation-reduction potential and tryptophan metabolism in primed pluripotency

    , Article Cell and Bioscience ; Volume 9, Issue 1 , 2019 ; 20453701 (ISSN) Yousefi, M ; Marashi, S. A ; Sharifi Zarchi, A ; Taleahmad, S ; Sharif University of Technology
    BioMed Central Ltd  2019
    Abstract
    Background: Pluripotency is proposed to exist in two different stages: Naive and Primed. Conventional human pluripotent cells are essentially in the primed stage. In recent years, several protocols have claimed to generate naive human embryonic stem cells (hESCs). To the best of our knowledge, none of these protocols is currently recognized as the gold standard method. Furthermore, the consistency of the resulting cells from these diverse protocols at the molecular level is yet to be shown. Additionally, little is known about the principles that govern the metabolic differences between naive and primed pluripotency. In this work, using a computational approach, we tried to shed light on... 

    Single-Cell RNA-seq Dropout Imputation and Noise Reduction by Machine Learning

    , M.Sc. Thesis Sharif University of Technology Moinfar, Amir Ali (Author) ; Soleymani Baghshah, Mahdih (Supervisor) ; Sharifi Zarchi, Ali (Supervisor) ; Goodarzi, Hani (Co-Supervisor)
    Abstract
    Single-cell RNA sequencing (scRNA-seq) technologies have empowered us to study gene expressions at the single-cell resolution. These technologies are developed based on barcoding of single cells and sequencing of transcriptome using next-generation sequencing technologies. Achieving this single-cell resolution is specially important when the target population is complex or heterogeneous, which is the case for most biological samples, including tissue samples and tumor biopsies.Single-cell technologies suffer from high amounts of noise and missing values, generally known as dropouts. This complexity can affect a number of key downstream analyses such as differential expression analysis,...