Research
The Wang lab integrates advanced sequencing and high-performance computational genomics to enable precision medicine in diverse healthcare settings and populations. Our main focus is development of technologies to support faster, more accurate, and resource-appropriate molecular diagnostics for cancer and microbial pathogens.
As a part of UNC RAISE, a primary goal is the development of sequencing and computational technologies to enable precision cancer diagnostics in low-resource settings
Pediatric cancer classification
Comprehensive clinical diagnosis of childhood cancers relies on multiple costly and time-consuming techniques such as immunohistochemistry (IHC), flow cytometry, cytogenetics, fluorescence in situ hybridization (FISH), targeted PCR panels, and microarrays. Nanopore RNA-sequencing represents a potential alternative to flow cytometry, IHC, and cytogenetic approaches in low-resource settings. Clinically-relevant characterization, including cell lineage and genomic subtype, are made from low-coverage transcriptome profiling via a machine learning classifier.
Wang et al, 2022 Opoku et al, 2024Metagenomics and genomic epidemiology
Single-molecule sequencing of metagenomes produces more specific taxonomic and genic characterization than standard NGS, but challenges remain due to relatively low throughput and high error rate, particularly from host-associated microbial communities. We have developed novel sequencing and informatics approaches to increase throughput and classification accuracy in both synthetic and human tissue-associated microbiota.
Wang et al, 2021Genomic epidemiology of SARS-CoV-2 and anti-microbial resistance
Wang et al. 2022. Tegha et al. 2020.
Recent Publications
Pediatric cancer genomics and diagnostics
Opoku KB, Santiago T, Kumar P, Roush SM, Fedoriw Y, Tomoka T, Leventaki V, Furtado LV, Bhakta N, Alexander TB, Wang JR. Transcriptome profiling of pediatric extracranial solid tumors and lymphomas enables rapid low-cost diagnostic classification. Sci Rep 14, 19456 (2024).
https://doi.org/10.1038/s41598-024-70541-0
Chang T, Chen W, Qu C, Cheng Z, Hedges D, Elsayed A, Pounds SB, Shago M, Rabin KR, Raetz EA, Devidas M, Cheng C, Angiolillo A, Baviskar P, Borowitz M, Burke MJ, Carroll A, Carroll WL, Chen I, Harvey R, Heerema N, Iacobucci I, Wang JR, Jeha S, Larsen E, Mattano L, Maloney K, Pui C, Ramirez NC, Salzer W, Willman C, Winick N, Wood B, Hunger SP, Wu G, Mullighan CG, Loh ML. Genomic determinants of outcome in B acute lymphoblastic leukemia. Journal of Clinical Oncology. 0, JCO.23.02238.
https://doi.org/10.1200/JCO.23.02238
Aijaz J, Naseer F, Hussain S, Rafie Raza M, Jamal S, Ashraf S, Furtado L, Bhakta N, Alexander TB, Wang J. Feasibility and Accuracy of Nanopore Transcriptome Sequencing for Pediatric Acute Leukemia Lineage Classification in a Resource-Constrained Setting. America Society of Hematology Annual Conference. December 2023.
Opoku K, Santiago T, Bhakta N, Alexander TB, Wang J. Transcriptome profiling of pediatric extracranial solid tumors enables rapid, low cost diagnostic classification. Oral Presentation. American Society of Human Genetics Annual Meeting, 2023
Wang J, Kumar P, Santiago T, Fedoriw Y, Roush S, Jones C, Mullighan CG, Bhakta N, Alexander TB. Classification of Pediatric Extracranial Solid Tumors Using Low-Cost Nanopore RNA Sequencing of Formalin-Fixed Paraffin-Embedded Specimens. International Society of Pediatric Oncology Annual Conference. Poster Presentation. October 2022
Wang J, Bhakta N, Ayer Miller V, Revsine M, Litzow MR, Paietta E, Fedoriw Y, Roberts KG, Gu Z, Mullighan CG, Jones CD, Alexander TB. Acute Leukemia Classification Using Transcriptional Profiles From Low-Cost Nanopore mRNA Sequencing. JCO Precis Oncol. 2022 Apr;6:e2100326.
https://doi.org/10.1200/po.21.00326
Wang J, Bhakta N, Miller VA, Revsine M, Litzow MR, Paietta E, Roberts KG, Gu Z, Mullighan CG, Jones CD, Alexander TB. Nanopore RNA Sequencing As a Diagnostic Tool For Acute Leukemia In Low Resource Settings. International Society of Pediatric Oncology Annual Conference. Oral Presentation. October 24, 2021
Habashy C, Fedoriw Y, Ozawa S, Wang J, Aijaz J, Jamal S, Ashraf S, Lucha TA, Alabí SLF, Vasquez R, Mullighan CG, Metzger M, Jeha S, Rodriquez-Galindo C, Bhakta N, Alexander TB. Comparative Costs in Diagnostic Evaluation of Acute Leukemia in the United States and Two Lower-Middle Income Countries. Nanopore RNA Sequencing As a Diagnostic Tool For Acute Leukemia In Low Resource Settings. International Society of Pediatric Oncology Annual Conference. Oral Presentation. October 24, 2021
Zhao Y, Aldoss I, Qu C, Crawford JC, Gu Z, Allen EK, Zamora AE, Alexander TB, Wang J, Goto H, Imamura T, Akahane T, Marcucci G, Stein AS, Bhatia R, Thomas P, Forman SJ, Mullighan CG, Roberts KG. Tumor intrinsic and extrinsic determinants of response to blinatumomab in adults with B-ALL. Blood, 2020, blood.2020006287.
https://doi.org/10.1182/blood.2020006287
Microbial genomics and epidemiology
Roca C, Alkhateeb AA, Deanhardt BK, Macdonald JK, Chi DL, Wang JR, Wolfgang MC. (2024) Saliva sampling method influences oral microbiome composition and taxa distribution associated with oral diseases. PLoS ONE 19(3): e0301016.
https://doi.org/10.1371/journal.pone.0301016
Forry SP, Servetas SL, Kralj JG, Soh K, Hadjithomas M, Cano R, Carlin M, de Amorim MG, Auch B, Bakker MG, Bartelli TF, Bustamante JP, Cassol I, Chalita M, Dias-Neto E, Del Duca A, Gohl DM, Kazantseva J, Haruna MT, Menzel P, Moda BS, Neuberger-Castillo L, Nunes DN, Patel IR, Peralta RD, Saliou A, Schwarzer R, Sevilla S, Takenaka IKTM, Wang JR, Knight R, Gevers D, Jackson SA. Variability and Bias in Microbiome Metagenomic Sequencing: an Interlaboratory Study Comparing Experimental Protocols. Scientific Reports 14, 9785 (2024).
https://doi.org/10.1038/s41598-024-57981-4
Meganck RM, Edwards CE, Mallory ML, Lee RE, Dang H, Bailey AB, Wykoff JA, Gallant SC, Zhu DR, Yount BL, Kato T, Shaffer KM, Nakano S, Cawley AM, Sontake V, Wang JR, Hagan RS, Miller MB, Tata PR, Tse LV, Randell SH, Ehre C, Okuda K, Boucher RC, Baric RS. SARS-CoV-2 Variant of Concern Fitness and Adaptation in Primary Human Airway Epithelia. Cell Reports Volume 43, ISSUE 4, 114076, April 23, 2024.
https://doi.org/10.1016/j.celrep.2024.114076
Mak QXC, Wick R, Holt JM, Wang JR. Polishing de novo nanopore assemblies of bacteria and eukaryotes with FMLRC2. Molecular Biology and Evolution. Volume 40, Issue 3, March 2023, msad048.
https://doi.org/10.1093/molbev/msad048
Hakim J, Waltmann A, Tinajeros F, Kharabora O, Machaca EM, Calderon M, del Carmen Menduiña M, Wang J, Rueda D, Zimic M, Verástegui M, Juliano JJ, Gilman RH, Mugnier MR, Bowman NM, Chagas working group. Amplicon sequencing reveals complex infection in infants congenitally infected with Trypanosoma cruzi and informs the dynamics of parasite transmission. The Journal of Infectious Diseases. 2023; 228 (6), 769-776.
https://doi.org/10.1093/infdis/jiad125
Wang J, Hawken SE, Jones CD, Hagan RS, Bushman F, Everett J, Miller MB, Rodino KG. Collaboration between clinical and academic laboratories for sequencing SARS-CoV-2 genomes. Journal of Clinical Microbiology. 2022.
https://doi.org/10.1128/JCM.01288-21
Tegha G, Ciccone EJ, Krysiak R, Kaphatika J, Chikaonda R, Ndhlovu I, van Duin D, Hoffman I, Juliano JJ#, Wang J#. Genomic epidemiology of Escherichia coli isolates from a tertiary referral center in Lilongwe, Malawi. Microbial Genomics. 2021; Jan; 7(1).
https://doi.org/10.1099/mgen.0.000490
Wang J, Bleich RM, Zarmer S, Zhang S, Dogan B, et al. Long-read sequencing to interrogate strain-level variation among adherent-invasive Escherichia coli isolated from human intestinal tissue. PLOS ONE. 2021; 16(10): e0259141.
https://doi.org/10.1371/journal.pone.0259141
Lopez LR, Barlogio CJ, Broberg CA, Wang J, Arthur JC. A nadA mutation confers nicotinic acid auxotrophy in pro-carcinogenic intestinal Escherichia coli NC101. Frontiers in Microbiology, 2021, 12, 1081.
https://doi.org/10.3389/fmicb.2021.670005
