High-throughput identification of novel conotoxins from the Chinese tubular cone snail (Conus betulinus) by multi-transcriptome sequencing

The primary objective of this study was to realize the large-scale discovery of conotoxin sequences from different organs (including the venom duct, venom bulb and salivary gland) of the vermivorous Oak cone snail, Conus quercinus. Using high-throughput transcriptome sequencing, we identified 133 putative conotoxins that belong to 34 known superfamilies, of which nine were previously reported while the remaining 124 were novel conotoxins, with 17 in new and unassigned conotoxin groups. A-, O1-, M-, and I2- superfamilies were the most abundant, and the cysteine frameworks XIII and VIII were observed for the first time in the A- and I2-superfamilies. The transcriptome data from the venom duct, venom bulb and salivary gland showed considerable inter-organizational variations. Each organ had many exclusive conotoxins, and only seven of all the inferred mature peptides were common in the three organs. As expected, most of the identified conotoxins were synthesized in the venom duct at relatively high levels; however, a number of conotoxins were also identified in the venom bulb and the salivary gland with very low transcription levels. Therefore, various organs have different conotoxins with high diversity, suggesting greater contributions from several organs to the high-throughput discovery of new conotoxins for future drug development.

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High throughput identification and validation of novel conotoxins from the chinese tubular cone snail (Conus betulinus)

Toxicon ◽

10.1016/j.toxicon.2018.10.219 ◽

2019 ◽

Vol 158 ◽

pp. S64

Author(s):

Chao Peng ◽

Bingmiao Gao ◽

Qiong Shi

Keyword(s):

High Throughput ◽

Cone Snail ◽

Conus Betulinus

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Supplementary data for: High-Throughput Transcriptome Sequencing for SNP and Gene Discovery in a Moth

Environmental Entomology ◽

10.1603/en11216sd2 ◽

2012 ◽

Vol 41 (4) ◽

Author(s):

Nicholas Miller

Keyword(s):

High Throughput ◽

Transcriptome Sequencing ◽

Gene Discovery ◽

Supplementary Data

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Diversity of Conopeptides and Conoenzymes from the Venom Duct of the Marine Cone Snail Conus bayani as Determined from Transcriptomic and Proteomic Analyses

Marine Drugs ◽

10.3390/md19040202 ◽

2021 ◽

Vol 19 (4) ◽

pp. 202

Author(s):

Rajesh Rajaian Pushpabai ◽

Carlton Ranjith Wilson Alphonse ◽

Rajasekar Mani ◽

Deepak Arun Apte ◽

Jayaseelan Benjamin Franklin

Keyword(s):

Gene Family ◽

Transcriptome Sequencing ◽

Cone Snail ◽

Active Peptides ◽

Transcriptomic Data ◽

Sequencing Technologies ◽

Hunting Strategies ◽

Divergent Gene ◽

Pharmacologically Active ◽

Highly Evolved

Marine cone snails are predatory gastropods characterized by a well-developed venom apparatus and highly evolved hunting strategies that utilize toxins to paralyze prey and defend against predators. The venom of each species of cone snail has a large number of pharmacologically active peptides known as conopeptides or conotoxins that are usually unique in each species. Nevertheless, venoms of only very few species have been characterized so far by transcriptomic approaches. In this study, we used transcriptome sequencing technologies and mass spectrometric methods to describe the diversity of venom components expressed by a worm-hunting species, Conus bayani. A total of 82 conotoxin sequences were retrieved from transcriptomic data that contain 54 validated conotoxin sequences clustered into 21 gene superfamilies including divergent gene family, 17 sequences clustered to 6 different conotoxin classes, and 11 conotoxins classified as unassigned gene family. Seven new conotoxin sequences showed unusual cysteine patterns. We were also able to identify 19 peptide sequences using mass spectrometry that completely overlapped with the conotoxin sequences obtained from transcriptome analysis. Importantly, herein we document the presence of 16 proteins that include five post-translational modifying enzymes obtained from transcriptomic data. Our results revealed diverse and novel conopeptides of an unexplored species that could be used extensively in biomedical research due to their therapeutic potentials.

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Discovery Methodology of Novel Conotoxins from Conus Species

Marine Drugs ◽

10.3390/md16110417 ◽

2018 ◽

Vol 16 (11) ◽

pp. 417 ◽

Cited By ~ 8

Author(s):

Ying Fu ◽

Cheng Li ◽

Shuai Dong ◽

Yong Wu ◽

Dongting Zhangsun ◽

...

Keyword(s):

Drug Development ◽

Gene Cloning ◽

High Throughput ◽

Disulfide Bond ◽

Cone Snail ◽

Crude Venom ◽

Drug Candidates ◽

Conus Species ◽

New Drug Development ◽

Natural Peptides

Cone snail venoms provide an ideal resource for neuropharmacological tools and drug candidates discovery, which have become a research hotspot in neuroscience and new drug development. More than 1,000,000 natural peptides are produced by cone snails, but less than 0.1% of the estimated conotoxins has been characterized to date. Hence, the discovery of novel conotoxins from the huge conotoxin resources with high-throughput and sensitive methods becomes a crucial key for the conotoxin-based drug development. In this review, we introduce the discovery methodology of new conotoxins from various Conus species. It focuses on obtaining full N- to C-terminal sequences, regardless of disulfide bond connectivity through crude venom purification, conotoxin precusor gene cloning, venom duct transcriptomics, venom proteomics and multi-omic methods. The protocols, advantages, disadvantages, and developments of different approaches during the last decade are summarized and the promising prospects are discussed as well.

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Organoid Models for Cancer Research

Annual Review of Cancer Biology ◽

10.1146/annurev-cancerbio-030518-055702 ◽

2019 ◽

Vol 3 (1) ◽

pp. 223-234 ◽

Cited By ~ 9

Author(s):

Hans Clevers ◽

David A. Tuveson

Keyword(s):

Cancer Research ◽

Tumor Microenvironment ◽

Personalized Medicine ◽

High Throughput ◽

Stromal Cells ◽

Transcriptome Sequencing ◽

Cancer Biology ◽

Three Dimensional ◽

Model Systems ◽

Liver Cancers

Organoid cultures have emerged as powerful model systems accelerating discoveries in cellular and cancer biology. These three-dimensional cultures are amenable to diverse techniques, including high-throughput genome and transcriptome sequencing, as well as genetic and biochemical perturbation, making these models well suited to answer a variety of questions. Recently, organoids have been generated from diverse human cancers, including breast, colon, pancreas, prostate, bladder, and liver cancers, and studies involving these models are expanding our knowledge of the etiology and characteristics of these malignancies. Co-cultures of cancer organoids with non-neoplastic stromal cells enable investigation of the tumor microenvironment. In addition, recent studies have established that organoids have a place in personalized medicine approaches. Here, we describe the application of organoid technology to cancer discovery and treatment.

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Unpuréeing the Tomato: Layers of Information Revealed by Microdissection and High-Throughput Transcriptome Sequencing

The Plant Cell ◽

10.1105/tpc.111.231111 ◽

2011 ◽

Vol 23 (11) ◽

pp. 3868-3868 ◽

Cited By ~ 4

Author(s):

Jennifer Mach

Keyword(s):

High Throughput ◽

Transcriptome Sequencing

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Screening of the candidate genes related to low-temperature tolerance of Fenneropenaeus chinensis based on high-throughput transcriptome sequencing

PLoS ONE ◽

10.1371/journal.pone.0211182 ◽

2019 ◽

Vol 14 (4) ◽

pp. e0211182 ◽

Cited By ~ 2

Author(s):

Xianhong Meng ◽

Lijun Dong ◽

Xiaoli Shi ◽

Xupeng Li ◽

Juan Sui ◽

...

Keyword(s):

Low Temperature ◽

Candidate Genes ◽

High Throughput ◽

Transcriptome Sequencing ◽

Fenneropenaeus Chinensis ◽

Temperature Tolerance ◽

Low Temperature Tolerance

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Venomic Interrogation Reveals the Complexity of Conus striolatus Venom

Australian Journal of Chemistry ◽

10.1071/ch19588 ◽

2020 ◽

Vol 73 (4) ◽

pp. 357

Author(s):

S. W. A. Himaya ◽

Subash K. Rai ◽

Giulia Pamfili ◽

Ai-Hua Jin ◽

Paul F. Alewood ◽

...

Keyword(s):

Potassium Channels ◽

High Throughput ◽

Proteomic Analysis ◽

Cone Snail ◽

Post Translational Modifications ◽

Peptide Processing ◽

Sodium Calcium ◽

Venom Composition ◽

Evolutionary Trajectories ◽

Similar Gene

Given the complexity of cone snail venoms, high throughput venomics approaches are required to fully investigate venom composition, envenomation strategies, and evolutionary trajectories. This study describes 158 conotoxins in the venom transcriptome of the little studied C. striolatus from the fish hunting clade Pionoconus. Despite similar gene superfamily distributions along the venom duct, only 18 common transcripts were identified between distal, central, and proximal venom duct transcriptomes. Proteomic analysis of the injected predatory venom collected from the same individual revealed an ~18-fold enhanced complexity at the proteomic level, consistent with complex post-translational modifications and variable venom peptide processing occurring in the venom duct. Overall, C. striolatus venom was dominated by M, O1, O2, and A gene superfamily conotoxins and conkunitzins, which are potential modulators of sodium, calcium, and potassium channels. Conkunitzins and gene superfamily A peptides dominated the proximal over the distal duct, the M and O1 gene superfamily peptides were distributed along the full length of the duct, while the O2 gene superfamily peptides dominated the distal duct. Interestingly, the predatory injected venom of C. striolatus was dominated by peptides from gene superfamilies M, O1, O2, A, and conkunitzins, suggesting the predatory venom of C. striolatus may arise at multiple sites along the venom duct.

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