Browsing by Author "Kaplan, Oktay, I"

Now showing 1 - 7 of 7

Citation - WoS: 3
Citation - Scopus: 3
MSABrowser: Dynamic and Fast Visualization of Sequence Alignments, Variations and Annotations
(Oxford Univ Press, 2021) Torun, Furkan M.; Bilgin, Halil, I; Kaplan, Oktay, I
Sequence alignment is an excellent way to visualize the similarities and differences between DNA, RNA or protein sequences, yet it is currently difficult to jointly view sequence alignment data with genetic variations, modifications such as post-translational modifications and annotations (i.e. protein domains). Here, we present the MSABrowser tool that makes it easy to co-visualize genetic variations, modifications and annotations on the respective positions of amino acids or nucleotides in pairwise or multiple sequence alignments. MSABrowser is developed entirely in JavaScript and works on any modern web browser at any platform, including Linux, Mac OS X and Windows systems without any installation. MSABrowser is also freely available for the benefit of the scientific community.
Citation - WoS: 3
Citation - Scopus: 4
Matching Variants for Functional Characterization of Genetic Variants
(Oxford Univ Press inc, 2023) Cevik, Sebiha; Zhao, Pei; Zorluer, Atiyye; Pir, Mustafa S.; Bian, Wenyin; Kaplan, Oktay, I
Rapid and low-cost sequencing, as well as computer analysis, have facilitated the diagnosis of many genetic diseases, resulting in a substantial rise in the number of disease-associated genes. However, genetic diagnosis of many disorders remains problematic due to the lack of interpretation for many genetic variants, especially missenses, the infeasibility of high-throughput experiments on mammals, and the shortcomings of computational prediction technologies. Additionally, the available mutant databases are not well-utilized. Toward this end, we used Caenorhabditis elegans mutant resources to delineate the functions of eight missense variants (V444I, V517D, E610K, L732F, E817K, H873P, R1105K, and G1205E) and two stop codons (W937stop and Q1434stop), including several matching variants (MatchVar) with human in ciliopathy associated IFT-140 (also called CHE-11)//IFT140 (intraflagellar transport protein 140). Moreover, MatchVars carrying C. elegans mutants, including IFT-140(G680S) and IFT-140(P702A) for the human (G704S) (dbSNP: rs150745099) and P726A (dbSNP: rs1057518064 and a conflicting variation) were created using CRISPR/Cas9. IFT140 is a key component of IFT complex A (IFT-A), which is involved in the retrograde transport of IFT along cilia and the entrance of G protein-coupled receptors into cilia. Functional analysis of all 10 variants revealed that P702A and W937stop, but not others phenocopied the ciliary phenotypes (short cilia, IFT accumulations, mislocalization of membrane proteins, and cilia entry of nonciliary proteins) of the IFT-140 null mutant, indicating that both P702A and W937stop are phenotypic in C. elegans. Our functional data offered experimental support for interpreting human variants, by using ready-to-use mutants carrying MatchVars and generating MatchVars with CRISPR/Cas9.
Citation - WoS: 10
Citation - Scopus: 12
Ciliaminer: An Integrated Database for Ciliopathy Genes and Ciliopathies
(Oxford Univ Press, 2023) Turan, Merve Guel; Orhan, Mehmet Emin; Cevik, Sebiha; Kaplan, Oktay, I
Cilia are found in eukaryotic species ranging from single-celled organisms, such as Chlamydomonas reinhardtii, to humans, but not in plants. The ability to respond to repellents and/or attractants, regulate cell proliferation and differentiation and provide cellular mobility are just a few examples of how crucial cilia are to cells and organisms. Over 30 distinct rare disorders generally known as ciliopathy are caused by abnormalities or functional impairments in cilia and cilia-related compartments. Because of the complexity of ciliopathies and the rising number of ciliopathies and ciliopathy genes, a ciliopathy-oriented and up-to-date database is required. Here, we present CiliaMiner, a manually curated ciliopathy database that includes ciliopathy lists collected from articles and databases. Analysis reveals that there are 55 distinct disorders likely related to ciliopathy, with over 4000 clinical manifestations. Based on comparative symptom analysis and subcellular localization data, diseases are classified as primary, secondary or atypical ciliopathies. CiliaMiner provides easy access to all of these diseases and disease genes, as well as clinical features and gene-specific clinical features, as well as subcellular localization of each protein. Additionally, the orthologs of disease genes are also provided for mice, zebrafish, Xenopus, Drosophila, Caenorhabditis elegans and Chlamydomonas reinhardtii. CiliaMiner (https://kaplanlab.shinyapps.io/ciliaminer) aims to serve the cilia community with its comprehensive content and highly enriched interactive heatmaps, and will be continually updated.
Citation - WoS: 13
Citation - Scopus: 11
Ciliogenics: An Integrated Method and Database for Predicting Novel Ciliary Genes
(Oxford Univ Press, 2024) Pir, Mustafa S.; Begar, Efe; Yenisert, Ferhan; Demirci, Hasan C.; Korkmaz, Mustafa E.; Karaman, Asli; Kaplan, Oktay, I
Uncovering the full list of human ciliary genes holds enormous promise for the diagnosis of cilia-related human diseases, collectively known as ciliopathies. Currently, genetic diagnoses of many ciliopathies remain incomplete (). While various independent approaches theoretically have the potential to reveal the entire list of ciliary genes, approximately 30% of the genes on the ciliary gene list still stand as ciliary candidates (,). These methods, however, have mainly relied on a single strategy to uncover ciliary candidate genes, making the categorization challenging due to variations in quality and distinct capabilities demonstrated by different methodologies. Here, we develop a method called CilioGenics that combines several methodologies (single-cell RNA sequencing, protein-protein interactions (PPIs), comparative genomics, transcription factor (TF) network analysis, and text mining) to predict the ciliary capacity of each human gene. Our combined approach provides a CilioGenics score for every human gene that represents the probability that it will become a ciliary gene. Compared to methods that rely on a single method, CilioGenics performs better in its capacity to predict ciliary genes. Our top 500 gene list includes 258 new ciliary candidates, with 31 validated experimentally by us and others. Users may explore the whole list of human genes and CilioGenics scores on the CilioGenics database (https://ciliogenics.com/). Graphical Abstract
Citation - WoS: 18
Citation - Scopus: 17
ConVarT: A Search Engine for Matching Human Genetic Variants With Variants From Non-Human Species
(Oxford Univ Press, 2022) Pir, Mustafa S.; Bilgin, Halil, I; Sayici, Ahmet; Torun, Furkan M.; Zhao, Pei; Kang, Yahong; Kaplan, Oktay, I
The availability of genetic variants, togetherwith phenotypic annotations from model organisms, facilitates comparing these variants with equivalent variants in humans. However, existing databases and search tools do not make it easy to scan for equivalent variants, namely 'matching variants' (MatchVars) between humans and other organisms. Therefore, we developed an integrated search engine called ConVarT (http://www.convart.org/) for matching variants between humans, mice, and Caenorhabditis elegans. ConVarT incorporates annotations (including phenotypic and pathogenic) into variants, and these previously unexploited phenotypic MatchVars from mice and C. elegans can give clues about the functional consequence of human genetic variants. Our analysis shows that many phenotypic variants in different genes from mice and C. elegans, so far, have no counterparts in humans, and thus, can be useful resources when evaluating a relationship between a new human mutation and a disease.
Citation - WoS: 1
Citation - Scopus: 2
Protocol for Determining the Average Speed and Frequency of Kinesin and Dynein-Driven Intraflagellar Transport (IFT) in C. Elegans
(Elsevier, 2022) Turan, Merve G.; Kantarci, Hanife; Temtek, Sadiye D.; Cakici, Onur; Cevik, Sebiha; Kaplan, Oktay, I
Here, we present a protocol to image a fluorescent-labeled intraflagellar trans-port (IFT) component in Caenorhabditis elegans with fluorescence microscopy, including steps of sample preparations, in vivo live-cell imaging, and post -micro-scopy analysis with kymographs. This protocol breaks down all processes into three categories: (1) pre-imaging preparations, (2) preparations for the time of image acquisition, and (3) post-imaging analyses. The protocol can be applied to determine the speed and frequency of moving particles. For complete details on the use and execution of this protocol, please refer to Cevik et al. (2021).
Citation - WoS: 5
Citation - Scopus: 5
WDR31 Displays Functional Redundancy With GTpase-Activating Proteins (GAPs) ELMOD and RP2 in Regulating Ift Complex and Recruiting the BBsome to Cilium
(Life Science Alliance Llc, 2023) Cevik, Sebiha; Peng, Xiaoyu; Beyer, Tina; Pir, Mustafa S.; Yenisert, Ferhan; Woerz, Franziska; Kaplan, Oktay, I
The correct intraflagellar transport (IFT) assembly at the ciliary base and the IFT turnaround at the ciliary tip are key for the IFT to perform its function, but we still have poor understanding about how these processes are regulated. Here, we identify WDR31 as a new ciliary protein, and analysis from zebrafish and Caeno-rhabditis elegans reveals the role of WDR31 in regulating the cilia morphology. We find that loss of WDR-31 together with RP-2 and ELMD-1 (the sole ortholog ELMOD1-3) results in ciliary accumu-lations of IFT Complex B components and KIF17 kinesin, with fewer IFT/BBSome particles traveling along cilia in both anterograde and retrograde directions, suggesting that the IFT/BBSome entry into the cilia and exit from the cilia are impacted. Furthermore, anterograde IFT in the middle segment travels at increased speed in wdr-31;rpi-2;elmd-1. Remarkably, a non-ciliary protein leaks into the cilia of wdr-31;rpi-2;elmd-1, possibly because of IFT de-fects. This work reveals WDR31-RP-2-ELMD-1 as IFT and BBSome trafficking regulators.