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1. ICML Topological Deep Learning Challenge 2024: Beyond the Graph Domain

Author

Bernárdez, Guillermo, Telyatnikov, Lev, Montagna, Marco, Baccini, Federica, Papillon, Mathilde, Ferriol-Galmés, Miquel, Hajij, Mustafa, Papamarkou, Theodore, Bucarelli, Maria Sofia, Zaghen, Olga, Mathe, Johan, Myers, Audun, Mahan, Scott, Lillemark, Hansen, Vadgama, Sharvaree, Bekkers, Erik, Doster, Tim, Emerson, Tegan, Kvinge, Henry, Agate, Katrina, Ahmed, Nesreen K, Bai, Pengfei, Banf, Michael, Battiloro, Claudio, Beketov, Maxim, Bogdan, Paul, Carrasco, Martin, Cavallo, Andrea, Choi, Yun Young, Dasoulas, George, Elphick, Matouš, Escalona, Giordan, Filipiak, Dominik, Fritze, Halley, Gebhart, Thomas, Gil-Sorribes, Manel, Goomanee, Salvish, Guallar, Victor, Imasheva, Liliya, Irimia, Andrei, Jin, Hongwei, Johnson, Graham, Kanakaris, Nikos, Koloski, Boshko, Kovač, Veljko, Lecha, Manuel, Lee, Minho, Leroy, Pierrick, Long, Theodore, Magai, German, Martinez, Alvaro, Masden, Marissa, Mežnar, Sebastian, Miquel-Oliver, Bertran, Molina, Alexis, Nikitin, Alexander, Nurisso, Marco, Piekenbrock, Matt, Qin, Yu, Rygiel, Patryk, Salatiello, Alessandro, Schattauer, Max, Snopov, Pavel, Suk, Julian, Sánchez, Valentina, Tec, Mauricio, Vaccarino, Francesco, Verhellen, Jonas, Wantiez, Frederic, Weers, Alexander, Zajec, Patrik, Škrlj, Blaž, and Miolane, Nina

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence
Abstract

This paper describes the 2nd edition of the ICML Topological Deep Learning Challenge that was hosted within the ICML 2024 ELLIS Workshop on Geometry-grounded Representation Learning and Generative Modeling (GRaM). The challenge focused on the problem of representing data in different discrete topological domains in order to bridge the gap between Topological Deep Learning (TDL) and other types of structured datasets (e.g. point clouds, graphs). Specifically, participants were asked to design and implement topological liftings, i.e. mappings between different data structures and topological domains --like hypergraphs, or simplicial/cell/combinatorial complexes. The challenge received 52 submissions satisfying all the requirements. This paper introduces the main scope of the challenge, and summarizes the main results and findings., Comment: Proceedings of the Geometry-grounded Representation Learning and Generative Modeling Workshop (GRaM) at ICML 2024

Published
2024

4. Cover

Author

Johnson, Elizabeth Lominska and Johnson, Graham E.

Published
2019

6. Bibliography

Author

Johnson, Elizabeth Lominska and Johnson, Graham E.

Published
2019

11. Acknowledgements

Author

Johnson, Elizabeth Lominska and Johnson, Graham E.

Published
2019

16. 1. Getting Started

Author

Johnson, Elizabeth Lominska and Johnson, Graham E.

Published
2019

18. Illustrations

Author

Johnson, Elizabeth Lominska and Johnson, Graham E.

Published
2019

21. Alternatives to Contour Visualizations for Power Systems Data

Author

Lyons-Galante, Isaiah, Karimzadeh, Morteza, Molnar, Samantha, Johnson, Graham, and Gruchalla, Kenny

Subjects
Computer Science - Human-Computer Interaction
Abstract

Electrical grids are geographical and topological structures whose voltage states are challenging to represent accurately and efficiently for visual analysis. The current common practice is to use colored contour maps, yet these can misrepresent the data. We examine the suitability of four alternative visualization methods for depicting voltage data in a geographically dense distribution system -- Voronoi polygons, H3 tessellations, S2 tessellations, and a network-weighted contour map. We find that Voronoi tessellations and network-weighted contour maps more accurately represent the statistical distribution of the data than regular contour maps., Comment: IEEE Vis 2023

Published
2023

26. Tainted Love: A Systematic Review of Online Romance Fraud

Author

Bilz, Alexander, Shepherd, Lynsay A., and Johnson, Graham I.

Subjects
Computer Science - Human-Computer Interaction, Computer Science - Cryptography and Security, Computer Science - Computers and Society
Abstract

Romance fraud involves cybercriminals engineering a romantic relationship on online dating platforms. It is a cruel form of cybercrime whereby victims are left heartbroken, often facing financial ruin. We characterise the literary landscape on romance fraud, advancing the understanding of researchers and practitioners by systematically reviewing and synthesising contemporary qualitative and quantitative evidence. The systematic review provides an overview of the field by establishing influencing factors of victimhood and exploring countermeasures for mitigating romance scams. We searched ten scholarly databases and websites using terms related to romance fraud. Studies identified were screened, and high-level metadata and findings were extracted, synthesised, and contrasted. The methodology followed the PRISMA guidelines: a total of 232 papers were screened. Eighty-two papers were assessed for eligibility, and 44 were included in the final analysis. Three main contributions were identified: profiles of romance scams, countermeasures for mitigating romance scams, and factors that predispose an individual to become a scammer or a victim. Despite a growing corpus of literature, the total number of empirical or experimental examinations remained limited. The paper concludes with avenues for future research and victimhood intervention strategies for practitioners, law enforcement, and industry., Comment: 41 pages, 3 figures, 3 tables

Published
2023

29. Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial. The ABC-Sepsis Trial

Author

Gray, Alasdair J., Oatey, Katherine, Grahamslaw, Julia, Irvine, Sîan, Cafferkey, John, Kennel, Titouan, Norrie, John, Walsh, Tim, Lone, Nazir, Horner, Daniel, Appelboam, Andy, Hall, Peter, Skipworth, Richard J. E., Bell, Derek, Rooney, Kevin, Shankar-Hari, Manu, Corfield, Alasdair R., Newcombe, Virginia, Chapman, Robert, Hutton, Corinne, Perkins, Gavin, Gordon, Anthony, Keating, Liza, Pallmann, Philip, Armstrong, Ruth, Pollock, Roz, Wackett, Tony, Chapman, Robert, Hutton, Corrine, Kale, Jane, Kale, Neville, Anderson, Rory, Birrell, David, Black, Polly, Blackstock, Caroline, Carter, Jonathan, Clark, Donna, Davidson, Craig, Davie, Carlyn, Rollo, Nicola Di, Ferguson, Andrew, Fethers, Nicholas, Freeman, Nicola, Gibson, Louise, Grant, Alison, Harris, Marie-Clare, James, Ed, Letham, Katy, Lynch, Stephen, McCurrach, Fiona, McKenzie, Suzi, McLaughlin, Connor, Miell, Anna, Moncur, Lyle, O’Brien, Rachel, Pickering, Gillian, Reed, Matt, Rezai, Roozbeh, Robinson, Sara, Skinner, Janet, Walker, Craig, Williams, Alison, Wilson, Emma-Beth, Di Rollo, Nicola, Carruthers, Jennifer, Cheyne, Claire, McGeough, Angela, Lidstone-Scott, Rebecca, Lynch, Stephen, Abel, Lynn, Bongale, Santosh, Currie, Susie, Kane, Donna, Keen, Rachel, Orlikowska, Izabella, Rodden, Natalie, Tait, Jennifer, Thomson, Nicola, Walker, Lauren, Smith, Kate, Brown, Ammani, Cathcart, Susanne, Maguire, Donogh, O’Mailley, Patrick, Rimmer, Dominic, Ward, Catherine, Baxter, Nicola, Denny, Fraser, Doran, Kayleigh, Dunlop, Lisa, Dunn, Jessica, Finnen, Lisa, Green, Darren, Hughes, Emma, Lowe, David, McArthur, Courtney, McLaren, Barbara, McLeish, Kirsty, McMunigal, Linda, McParland, Chris, O’Shaughnessy, Ornagh, Wilson, Mark, Armes, Roland, Brown, Craig, Cooper, Jamie, Connor, David, Collier-Wakefield, Otto, Coutts, Mandi, Cruickshank, Mairi, Ebtehadj, Bianca, Ganley, Pauline, Hiscox, John, Hartman, Catharina, Kane, Leia, Kastora, Stavroula, Lamb, Sarah, McCarthy, Sinead, Mulholland, Conal, Nadim, Imran, Noble, Jennifer, Patton, Gareth, Savage, David, Spowage-Delaney, Benjamin, Doonan, Reece, Lee, Stephanie, Strange, Joshua, Barham, Ffion, Bosanko, Clare, Bullough, Richard, Danglosi, Joan, Freeman, Elaine, Jackson, Luci-Adele, James, Robert, Jose, Louise, Lowe, Fionna, Lowther, Ashleigh, McCarthy, Ian, McConnell, David, Parry, Richard, Shirreff, Henry, Smith, Jason, Squire, Rosalyn, Battishill, Wayne, Boggaram, Girish, Chilcott, Gemma, Gagg, James, Machin, Emma, Shovelton, Charmaine, Purnell, Rebecca, Crosthwaite-Eyre, Richard, Page, George, Pitt, Andrew, Riou, Peter, Sykes, Daisy, Worth, Cassie, Zitter, Lily, Baron, Tanya, Baskaran, Dineshbabu, Beer, Sally, Bhargav, Akshay, Blamey, Helen, Brown, Charlotte, Clare-Gray, Benjamin, Davies, Matthew, Dawson, Neil, Dineen, Karen, Edgar, Iain, Erasu, Vishakha, Faisal, Muhammad, Georgiou, Dominique, Gibson, Alice, Ghataoura, Rashpal, Glover, Samuel, Gordon, Olivia, Ilyas, Sadaf, Jeffs, Aimee, Knott, Henry, Kundoor, Sneha, Martinez, Jose, McCallum, Andrew, Novak, Alex, Panduro, Tine, Pattanshetty, Ravi, Paul, Immanuel, Magallano, Rufino Roger, Razdan, Pamposh, Sambo, Tinelly, Shah, Sumaiyah, Shaikh, Ayisha, Smith, Simon, Thraves, Hannah, Tickle, Charlotte, Ang, Justin, Boyle, Adrian, Hardwick, Susie, Meynell, Kerry, Miller, Samuel, Charsley, Julia, Jolly, Sarah, Mahony, Faye, Moseley-Rodgers, Jade, Sivayoham, Narani, Sheerin, Thomas, Seel, Claire, Abdalla, Mohamed, Cameron, Gregor, Harnett, James, Ramos, Daryl, Perez, Fabiola Sevilla, White, Rachel, Abdullah, Wajiha, Ballard, Suzanna, Barnes, Katie, Clegg, Rebecca, Cousins, Elisha, Cumiskey, Simon, Elwir, Bashar, Ferriman, Alexander, Fletcher, Alison, Griffiths, Charlotte, Guiling, Paolyn, Johnson, Graham, Loach, Benjamin, Matthews, Alison, May-Moulden, Lucy, Norman, Rebecca, Seelly, Helen, Smith, Richard, Tabner, Andrew, Tilbury, Nicholas, Ward, Thomas, Wright, Lianne, Wroblewski, Heather, and Zawadzka, Marcelina

Published
2024
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33. Preclinical validation of a potent γ-secretase modulator for Alzheimer’s disease prevention

Author

Rynearson, Kevin D, Ponnusamy, Moorthi, Prikhodko, Olga, Xie, Yuhuan, Zhang, Can, Nguyen, Phuong, Hug, Brenda, Sawa, Mariko, Becker, Ann, Spencer, Brian, Florio, Jazmin, Mante, Michael, Salehi, Bahar, Arias, Carlos, Galasko, Douglas, Head, Brian P, Johnson, Graham, Lin, Jiunn H, Duddy, Steven K, Rissman, Robert A, Mobley, William C, Thinakaran, Gopal, Tanzi, Rudolph E, and Wagner, Steven L

Subjects
Biomedical and Clinical Sciences, Alzheimer's Disease, Dementia, Aging, Neurodegenerative, Prevention, Acquired Cognitive Impairment, Brain Disorders, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Alzheimer Disease, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Animals, Cell Line, Tumor, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Female, Humans, Macaca fascicularis, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neuroblastoma, Peptide Fragments, Phenethylamines, Pyridazines, Rats, Rats, Sprague-Dawley, Signal Transduction, Treatment Outcome, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

A potent γ-secretase modulator (GSM) has been developed to circumvent problems associated with γ-secretase inhibitors (GSIs) and to potentially enable use in primary prevention of early-onset familial Alzheimer's disease (EOFAD). Unlike GSIs, GSMs do not inhibit γ-secretase activity but rather allosterically modulate γ-secretase, reducing the net production of Aβ42 and to a lesser extent Aβ40, while concomitantly augmenting production of Aβ38 and Aβ37. This GSM demonstrated robust time- and dose-dependent efficacy in acute, subchronic, and chronic studies across multiple species, including primary and secondary prevention studies in a transgenic mouse model. The GSM displayed a >40-fold safety margin in rats based on a comparison of the systemic exposure (AUC) at the no observed adverse effect level (NOAEL) to the 50% effective AUC or AUCeffective, the systemic exposure required for reducing levels of Aβ42 in rat brain by 50%.

Published
2021

36. Where to Look for Waste on The Sheet Metal Shop Floor: Cut down on material waste, downtime, inefficient workflows, excess inventory, and rework

Author

Johnson, Graham

Subjects
Sheet-metal work -- Management, Refuse and refuse disposal -- Methods, Company business management, Business, Construction and materials industries, Environmental services industry
Abstract

In the ever-evolving landscape of manufacturing, sheet metal shops are continuously seeking ways to enhance efficiency, reduce costs, and streamline processes. Identifying and eliminating waste is a crucial aspect of [...]

Published
2024

37. Integrated intracellular organization and its variations in human iPS cells

Author

Viana, Matheus P., Chen, Jianxu, Knijnenburg, Theo A., Vasan, Ritvik, Yan, Calysta, Arakaki, Joy E., Bailey, Matte, Berry, Ben, Borensztejn, Antoine, Brown, Eva M., Carlson, Sara, Cass, Julie A., Chaudhuri, Basudev, Cordes Metzler, Kimberly R., Coston, Mackenzie E., Crabtree, Zach J., Davidson, Steve, DeLizo, Colette M., Dhaka, Shailja, Dinh, Stephanie Q., Do, Thao P., Domingus, Justin, Donovan-Maiye, Rory M., Ferrante, Alexandra J., Foster, Tyler J., Frick, Christopher L., Fujioka, Griffin, Fuqua, Margaret A., Gehring, Jamie L., Gerbin, Kaytlyn A., Grancharova, Tanya, Gregor, Benjamin W., Harrylock, Lisa J., Haupt, Amanda, Hendershott, Melissa C., Hookway, Caroline, Horwitz, Alan R., Hughes, H. Christopher, Isaac, Eric J., Johnson, Gregory R., Kim, Brian, Leonard, Andrew N., Leung, Winnie W., Lucas, Jordan J., Ludmann, Susan A., Lyons, Blair M., Malik, Haseeb, McGregor, Ryan, Medrash, Gabe E., Meharry, Sean L., Mitcham, Kevin, Mueller, Irina A., Murphy-Stevens, Timothy L., Nath, Aditya, Nelson, Angelique M., Oluoch, Sandra A., Paleologu, Luana, Popiel, T. Alexander, Riel-Mehan, Megan M., Roberts, Brock, Schaefbauer, Lisa M., Schwarzl, Magdalena, Sherman, Jamie, Slaton, Sylvain, Sluzewski, M. Filip, Smith, Jacqueline E., Sul, Youngmee, Swain-Bowden, Madison J., Tang, W. Joyce, Thirstrup, Derek J., Toloudis, Daniel M., Tucker, Andrew P., Valencia, Veronica, Wiegraebe, Winfried, Wijeratna, Thushara, Yang, Ruian, Zaunbrecher, Rebecca J., Labitigan, Ramon Lorenzo D., Sanborn, Adrian L., Johnson, Graham T., Gunawardane, Ruwanthi N., Gaudreault, Nathalie, Theriot, Julie A., and Rafelski, Susanne M.

Published
2023
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38. Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators

Author

Rynearson, Kevin D, Buckle, Ronald N, Herr, R Jason, Mayhew, Nicholas J, Chen, Xinchao, Paquette, William D, Sakwa, Samuel A, Yang, Jinhai, Barnes, Keith D, Nguyen, Phuong, Mobley, William C, Johnson, Graham, Lin, Juinn H, Tanzi, Rudolph E, and Wagner, Steven L

Subjects
Medicinal and Biomolecular Chemistry, Chemical Sciences, Biotechnology, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Amyloid Precursor Protein Secretases, Amyloid beta-Peptides, Animals, Cell Line, Tumor, Dose-Response Relationship, Drug, Drug Design, Enzyme Inhibitors, Female, Humans, Male, Mice, Mice, Transgenic, Molecular Structure, Pyridines, Structure-Activity Relationship, Gamma secretase modulator, Alzheimer's disease, Amyloid beta, A beta 42 reduction, Structure activity relationship, Methoxypyridines, Alzheimer’s disease, Aβ42 reduction, Organic Chemistry, Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, Biochemistry and cell biology, Medicinal and biomolecular chemistry, Organic chemistry
Abstract

The evolution of gamma-secretase modulators (GSMs) through the introduction of novel heterocycles with the goal of aligning activity for reducing the levels of Aβ42 and properties consistent with a drug-like molecule are described. The insertion of a methoxypyridine motif within the tetracyclic scaffold provided compounds with improved activity for arresting Aβ42 production as well as improved properties, including solubility. In vivo pharmacokinetic analysis demonstrated that several compounds within the novel series were capable of crossing the BBB and accessing the therapeutic target. Treatment with methoxypyridine-derived compound 64 reduced Aβ42 levels in the plasma of J20 mice, in addition to reducing Aβ42 levels in the plasma and brain of Tg2576 mice.

Published
2020

40. Transcriptome and epigenome landscape of human cortical development modeled in organoids

Author

Amiri, Anahita, Coppola, Gianfilippo, Scuderi, Soraya, Wu, Feinan, Roychowdhury, Tanmoy, Liu, Fuchen, Pochareddy, Sirisha, Shin, Yurae, Safi, Alexias, Song, Lingyun, Zhu, Ying, Sousa, André MM, Gerstein, Mark, Crawford, Gregory E, Sestan, Nenad, Abyzov, Alexej, Vaccarino, Flora M, Akbarian, Schahram, An, Joon-Yong, Armoskus, Christoper, Ashley-Koch, Allison E, Beach, Thomas G, Belmont, Judson, Bendl, Jaroslav, Borrman, Tyler, Brown, Leanne, Brown, Miguel, Brown, Mimi, Brunetti, Tonya, Bryois, Julien, Burke, Emily E, Camarena, Adrian, Carlyle, Becky C, Chae, Yooree, Charney, Alexander W, Chen, Chao, Cheng, Lijun, Cherskov, Adriana, Choi, Jinmyung, Clarke, Declan, Collado-Torres, Leonardo, Dai, Rujia, De La Torre Ubieta, Luis, DelValle, Diane, Devillers, Olivia, Dracheva, Stella, Emani, Prashant S, Evgrafov, Oleg V, Farnham, Peggy J, Fitzgerald, Dominic, Flatow, Elie, Francoeur, Nancy, Fullard, John F, Gandal, Michael J, Gao, Tianliuyun, Garrett, Melanie E, Geschwind, Daniel H, Giase, Gina, Girdhar, Kiran, Giusti-Rodriguez, Paola, Goes, Fernando S, Goodman, Thomas, Grennan, Kay S, Gu, Mengting, Gürsoy, Gamze, Hadjimichael, Evi, Hahn, Chang-Gyu, Haroutunian, Vahram, Hauberg, Mads E, Hoffman, Gabriel E, Huey, Jack, Hyde, Thomas M, Ivanov, Nikolay A, Jacobov, Rivka, Jaffe, Andrew E, Jiang, Yan, Jiang, Yi, Johnson, Graham D, Kassim, Bibi S, Kefi, Amira, Kim, Yunjung, Kitchen, Robert R, Kleiman, Joel E, Knowles, James A, Kozlenkov, Alexey, Li, Mingfeng, Li, Zhen, Lipska, Barbara K, Liu, Chunyu, Liu, Shuang, Mangravite, Lara M, Mariani, Jessica, Mattei, Eugenio, Miller, Daniel J, Moore, Jill, Nairn, Angus C, Navarro, Fabio CP, Park, Royce B, Peters, Mette A, and Pinto, Dalila

Subjects
Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Embryonic - Human, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell, Human Genome, Intellectual and Developmental Disabilities (IDD), Autism, Brain Disorders, Biotechnology, Clinical Research, Mental Health, Pediatric, Neurosciences, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, 1.1 Normal biological development and functioning, Neurological, Cerebral Cortex, Enhancer Elements, Genetic, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Humans, Induced Pluripotent Stem Cells, Models, Neurological, Neurogenesis, Organoids, Transcriptome, PsychENCODE Consortium, General Science & Technology
Abstract

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.

Published
2018

41. Comprehensive functional genomic resource and integrative model for the human brain

Author

Wang, Daifeng, Liu, Shuang, Warrell, Jonathan, Won, Hyejung, Shi, Xu, Navarro, Fabio CP, Clarke, Declan, Gu, Mengting, Emani, Prashant, Yang, Yucheng T, Xu, Min, Gandal, Michael J, Lou, Shaoke, Zhang, Jing, Park, Jonathan J, Yan, Chengfei, Rhie, Suhn Kyong, Manakongtreecheep, Kasidet, Zhou, Holly, Nathan, Aparna, Peters, Mette, Mattei, Eugenio, Fitzgerald, Dominic, Brunetti, Tonya, Moore, Jill, Jiang, Yan, Girdhar, Kiran, Hoffman, Gabriel E, Kalayci, Selim, Gümüş, Zeynep H, Crawford, Gregory E, Roussos, Panos, Akbarian, Schahram, Jaffe, Andrew E, White, Kevin P, Weng, Zhiping, Sestan, Nenad, Geschwind, Daniel H, Knowles, James A, Gerstein, Mark B, Ashley-Koch, Allison E, Garrett, Melanie E, Song, Lingyun, Safi, Alexias, Johnson, Graham D, Wray, Gregory A, Reddy, Timothy E, Goes, Fernando S, Zandi, Peter, Bryois, Julien, Price, Amanda J, Ivanov, Nikolay A, Collado-Torres, Leonardo, Hyde, Thomas M, Burke, Emily E, Kleiman, Joel E, Tao, Ran, Shin, Joo Heon, Kundakovic, Marija, Brown, Leanne, Kassim, Bibi S, Park, Royce B, Wiseman, Jennifer R, Zharovsky, Elizabeth, Jacobov, Rivka, Devillers, Olivia, Flatow, Elie, Lipska, Barbara K, Lewis, David A, Haroutunian, Vahram, Hahn, Chang-Gyu, Charney, Alexander W, Dracheva, Stella, Kozlenkov, Alexey, Belmont, Judson, DelValle, Diane, Francoeur, Nancy, Hadjimichael, Evi, Pinto, Dalila, van Bakel, Harm, Fullard, John F, Bendl, Jaroslav, Hauberg, Mads E, Mangravite, Lara M, Peters, Mette A, Chae, Yooree, Peng, Junmin, Niu, Mingming, Wang, Xusheng, Webster, Maree J, Beach, Thomas G, Chen, Chao, and Jiang, Yi

Subjects
Human Genome, Biotechnology, Schizophrenia, Mental Health, Brain Disorders, Genetics, Neurosciences, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Underpinning research, Aetiology, Mental health, Brain, Datasets as Topic, Deep Learning, Enhancer Elements, Genetic, Epigenesis, Genetic, Epigenomics, Gene Expression Regulation, Gene Regulatory Networks, Genome-Wide Association Study, Humans, Mental Disorders, Quantitative Trait Loci, Single-Cell Analysis, Transcriptome, PsychENCODE Consortium, General Science & Technology
Abstract

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

Published
2018

42. Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder

Author

Gandal, Michael J, Zhang, Pan, Hadjimichael, Evi, Walker, Rebecca L, Chen, Chao, Liu, Shuang, Won, Hyejung, van Bakel, Harm, Varghese, Merina, Wang, Yongjun, Shieh, Annie W, Haney, Jillian, Parhami, Sepideh, Belmont, Judson, Kim, Minsoo, Moran Losada, Patricia, Khan, Zenab, Mleczko, Justyna, Xia, Yan, Dai, Rujia, Wang, Daifeng, Yang, Yucheng T, Xu, Min, Fish, Kenneth, Hof, Patrick R, Warrell, Jonathan, Fitzgerald, Dominic, White, Kevin, Jaffe, Andrew E, Peters, Mette A, Gerstein, Mark, Liu, Chunyu, Iakoucheva, Lilia M, Pinto, Dalila, Geschwind, Daniel H, Ashley-Koch, Allison E, Crawford, Gregory E, Garrett, Melanie E, Song, Lingyun, Safi, Alexias, Johnson, Graham D, Wray, Gregory A, Reddy, Timothy E, Goes, Fernando S, Zandi, Peter, Bryois, Julien, Price, Amanda J, Ivanov, Nikolay A, Collado-Torres, Leonardo, Hyde, Thomas M, Burke, Emily E, Kleiman, Joel E, Tao, Ran, Shin, Joo Heon, Akbarian, Schahram, Girdhar, Kiran, Jiang, Yan, Kundakovic, Marija, Brown, Leanne, Kassim, Bibi S, Park, Royce B, Wiseman, Jennifer R, Zharovsky, Elizabeth, Jacobov, Rivka, Devillers, Olivia, Flatow, Elie, Hoffman, Gabriel E, Lipska, Barbara K, Lewis, David A, Haroutunian, Vahram, Hahn, Chang-Gyu, Charney, Alexander W, Dracheva, Stella, Kozlenkov, Alexey, DelValle, Diane, Francoeur, Nancy, Roussos, Panos, Fullard, John F, Bendl, Jaroslav, Hauberg, Mads E, Mangravite, Lara M, Chae, Yooree, Peng, Junmin, Niu, Mingming, Wang, Xusheng, Webster, Maree J, Beach, Thomas G, Jiang, Yi, and Grennan, Kay S

Subjects
Pharmacology and Pharmaceutical Sciences, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Neurosciences, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Mental Illness, Bipolar Disorder, Mental Health, Schizophrenia, Biotechnology, Serious Mental Illness, Autism, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Autism Spectrum Disorder, Brain, Genetic Predisposition to Disease, Humans, Protein Isoforms, RNA Splicing, Sequence Analysis, RNA, Transcriptome, PsychENCODE Consortium, General Science & Technology
Abstract

Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.

Published
2018

43. Immobilisation of torus fractures of the wrist in children (FORCE): a randomised controlled equivalence trial in the UK

Author

Ahmad, Rahail, Alcock, Anastasia, Appelboam, Andrew, Armour, Lisa, Bayreuther, Jane, Beynon, Rhys, Brown, Charlotte, Cadman, Emily, Darlow, Nadine, Davis, Tessa, Gibson, Phoebe, Gilhooley, Colin, Gomes, Sylvester, Gough, Christopher, Hartin, David, Hartshorn, Stuart, Hussan, Temem (Tim), Jain, Neha, Jenkinson, Emma, Johnson, Graham, Kehler, Lisa, Long, Matthew, Lyttle, Mark, Manouchehri, Shahab, McKie, Christopher, Metcalfe, David, Morgans, Louise, Mullen, Niall, Novak, Alex, Nunn, Catherine, O'Hagan, Kath, Paul, Aman, Preston, Jennifer, Ramlakhan, Shammi, Somaskanthan, Aarani, Tan, Yok Weng, Thakker, Manish, Vemulapalli, Krishna, Weekes, Joanna, Westacott, Daniel, Wilson, Sarah, Wood, Darryl, Conner, Louise, Nicolaou, Nicolas, Monsell, Fergal, Perry, Daniel C, Achten, Juul, Knight, Ruth, Appelbe, Duncan, Dutton, Susan J, Dritsaki, Melina, Mason, James M, Roland, Damian T, Messahel, Shrouk, Widnall, James, and Costa, Matthew L

Published
2022
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45. Network signatures define consciousness state during focal seizures.

Author

Doss, Derek J., Johnson, Graham W., Makhoul, Ghassan S., Rashingkar, Rohan V., Shless, Jared S., Bibro, Camden E., Paulo, Danika L., Gummadavelli, Abhijeet, Ball, Tyler J., Reddy, Shilpa B., Naftel, Robert P., Haas, Kevin F., Dawant, Benoit M., Constantinidis, Christos, Williams Roberson, Shawniqua, Bick, Sarah K., Morgan, Victoria L., and Englot, Dario J.

Subjects
*CONVOLUTIONAL neural networks, *RAPID eye movement sleep, *FUNCTIONAL magnetic resonance imaging, *SEIZURES (Medicine), *PARTIAL epilepsy
Abstract

Objective: Epilepsy is a common neurological disorder affecting 1% of the global population. Loss of consciousness in focal impaired awareness seizures (FIASs) and focal‐to‐bilateral tonic–clonic seizures (FBTCSs) can be devastating, but the mechanisms are not well understood. Although ictal activity and interictal connectivity changes have been noted, the network states of focal aware seizures (FASs), FIASs, and FBTCSs have not been thoroughly evaluated with network measures ictally. Methods: We obtained electrographic data from 74 patients with stereoelectroencephalography (SEEG). Sliding window band power, functional connectivity, and segregation were computed on preictal, ictal, and postictal data. Five‐minute epochs of wake, rapid eye movement sleep, and deep sleep were also extracted. Connectivity of subcortical arousal structures was analyzed in a cohort of patients with both SEEG and functional magnetic resonance imaging (fMRI). Given that custom neuromodulation of seizures is predicated on detection of seizure type, a convolutional neural network was used to classify seizure types. Results: We found that in the frontoparietal association cortex, an area associated with consciousness, both consciousness‐impairing seizures (FIASs and FBTCSs) and deep sleep had increases in slow wave delta (1–4 Hz) band power. However, when network measures were employed, we found that only FIASs and deep sleep exhibited an increase in delta segregation and a decrease in gamma segregation. Furthermore, we found that only patients with FIASs had reduced subcortical‐to‐neocortical functional connectivity with fMRI versus controls. Finally, our deep learning network demonstrated an area under the curve of.75 for detecting consciousness‐impairing seizures. Significance: This study provides novel insights into ictal network measures in FASs, FIASs, and FBTCSs. Importantly, although both FIASs and FBTCSs result in loss of consciousness, our results suggest that ictal network changes in FIASs uniquely resemble those that occur during deep sleep. Our results may inform novel neuromodulation strategies for preservation of consciousness in epilepsy. [ABSTRACT FROM AUTHOR]

Published
2024
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46. The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy.

Author

Doss, Derek J, Shless, Jared S, Bick, Sarah K, Makhoul, Ghassan S, Negi, Aarushi S, Bibro, Camden E, Rashingkar, Rohan, Gummadavelli, Abhijeet, Chang, Catie, Gallagher, Martin J, Naftel, Robert P, Reddy, Shilpa B, Roberson, Shawniqua Williams, Morgan, Victoria L, Johnson, Graham W, and Englot, Dario J

Subjects
SEIZURES (Medicine), PARTIAL epilepsy, PRINCIPAL components analysis, ACADEMIC medical centers, PEOPLE with epilepsy
Abstract

Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the interictal suppression hypothesis posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8–13 Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analysed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the interictal suppression hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the interictal suppression hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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47. Empowering inflammatory bowel disease patients with at-home remote disease and therapeutic drug monitoring.

Author

Johnson, Graham

Abstract

Advances in the management of inflammatory bowel disease (IBD) are opening new possibilities for at-home and patient-led care, empowering individuals to take greater control of their condition. These developments are driving the adoption of remote sampling for therapeutic drug monitoring, which complements at-home subcutaneous therapies and faecal calprotectin testing for monitoring disease activity. This article explores how these innovations could enable patients to manage their disease from home, and what this could mean for the future of IBD management. [ABSTRACT FROM AUTHOR]

Published
2024
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