About

Miten Jain is an Assistant Professor in the Bioengineering department at Northeastern University College of Engineering, with a joint appointment in Physics. He joined the faculty in July 2022. His research focuses on nanopore technology, single-cell techniques, and computational biology. Jain's work includes the characterization of paired tumor and normal cell lines using long read sequencing, high-coverage sequencing of reference human genomes, and the adaptation of human ribosomal RNA for nanopore sequencing of canonical and modified nucleotides. His contributions have advanced the understanding of microbial communities in riverine environments and improved genome assembly techniques using nanopore sequencing. Jain has been recognized as a highly cited researcher and is among the top scientists worldwide based on citation impact.

Research topics

• Genetics
• Biology
• Computational biology
• Evolutionary biology
• Botany
• Nanotechnology
• Materials science

Selected publications

• Cytoplasmic localization of pseudouridine synthase 7 facilitates a pseudouridine-dependent enhancement of cellular stress tolerance

  Nature Communications · 2026-04-17 · 1 citations

  articleOpen access

  Pseudouridine (Ψ) is an abundant post-transcriptional modification found across all classes of RNA. It is widely speculated that Ψ inclusion in messenger RNAs (mRNAs) might provide an avenue for cells to control gene expression post-transcriptionally. Here we demonstrate that one of the principal mRNA pseudouridylating enzymes, pseudouridine synthase 7 (PUS7), exhibits a stress-induced accumulation in the cytoplasm of yeast and human epithelial lung cells. Stress-induced and cytoplasmic localization of PUS7 promotes Ψ-incorporation into hundreds of mRNA targets. In contrast, the modification status of tRNA sites targeted by PUS7 (Ψ13 and Ψ35) is unperturbed. Furthermore, engineered PUS7 cytoplasmic localization increases cellular fitness under reactive oxygen species (ROS) and divalent metal ion stress. Quantitative proteomics reveal a reshaping of the proteome upon PUS7 relocalization under stress. Collectively, our data demonstrate that PUS7 localization alters mRNA pseudouridylation patterns, reshapes the proteome, and influences cellular fitness. Pseudouridine is a widespread RNA modification implicated in the regulation of gene expression. Here, authors show that PUS7 relocalization changes mRNA pseudouridylation, reshapes the proteome, and enhances cell fitness.

  PublisherDOI

• P575: Scalable, routine, long read genome sequencing of undiagnosed rare disease samples*

  Genetics in Medicine Open · 2026-01-01

  articleOpen accessSenior author

  Variant Effect Predictor (VEP) for downstream validation and visualization.Future versions will include extended modules for handling partial exon disruptions, multi-transcript genes, and the integration of protein structure data for more granular functional predictions.Conclusion: CNVision offers a unified and reproducible approach to interpreting intragenic CNVs and their impact on gene function.By focusing on accurate annotation and functional prediction, it bridges the gap between tertiary variant analysis and clinical interpretation.Designed for future integration with transcriptomic and phenotypic data, CNVision enables comprehensive assessments of variant pathogenicity.As intragenic CNVs become increasingly recognized in genetic disorders, CNVision provides clinicians and researchers with a practical, scalable tool for the precise identification and classification of these variants.

  PublisherOA PDFDOI

• CurrentView: a tool for visualization and comparison of nanopore ionic current signals

  Bioinformatics · 2026-04-01

  articleOpen accessSenior author

  SUMMARY: Nanopore sequencing measures ionic current as native DNA or RNA molecules move through a biological pore. The resulting ionic current changes are inferred into sequence by Oxford Nanopore Technologies' Dorado basecaller. These data permit direct analysis of nucleotide sequences and modifications. The Dorado basecaller also outputs a move-table that contains approximate mappings between ionic current signal and basecalled sequence. This ionic current information can be visualized at specific positions given the alignment between a read sequence and a reference sequence. We present CurrentView, a fast and user-friendly toolkit for reference-guided visualization of nanopore ionic current signals. CurrentView uses conventional sequence alignment and move-table information from BAM files and signal information from ONT POD5 files to extract and visualize ionic current traces at specific positions. The toolkit supports simultaneous comparison across multiple experimental conditions, computes summary statistics through kernel density estimation and histograms, and enables visual analysis of signal patterns associated with modifications or sequence context. Notably, CurrentView can visualize and analyze more than two conditions at once. It supports UMAP dimensionality reduction and Gaussian Mixture Model (GMM) clustering, enabling the identification of distinct signal populations across experimental groups. CurrentView is available as both a Python API and an exploratory interactive web application, allowing researchers to rapidly inspect ionic current patterns and compare conditions. AVAILABILITY AND IMPLEMENTATION: CurrentView is fully open-source and available on GitHub https://github.com/genometechlab/currentview. The repository includes full documentation, an installation guide, usage instructions, and an example Jupyter notebook showing typical use cases similar to the one presented in the manuscript.

  PublisherDOI

• A complete human pancreatic cancer genome

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-06 · 1 citations

  articleOpen access

  Summary Cancer genome sequencing is essential for understanding tumor evolution and advancing precision medicine. 1 However, reference gaps and germline variants obscure detection of small and large somatic variants and methylation in repetitive regions. 1–3 It is common for tumor cells to gain or lose chromosome arms due to somatic structural changes that occur inside highly repetitive satellite DNA sequences in the centromeres. 4 To identify the full spectrum of somatic variants, including complex rearrangements, we construct and curate near-complete, haplotype-resolved assemblies of the most recent common ancestor of an early-passage broadly-consented hypodiploid pancreatic cancer cell line and matched normal tissues. The tumor assembly completely recapitulates all 35 tumor chromosomes observed with karyotyping, with multiple translocation-induced hybrid chromosomes. The hybrid chromosomes contain putative functional dicentric and fused centromeres, nested foldback inversions causing 14 breakpoints with a haplotype switch in a single event, and centromeric satellite tandem duplications up to 136 kbp. Direct comparison of tumor and normal assembly haplotypes uncovers >7,000 variants altering >1 Mbp of sequence in repetitive regions that have been hidden by reference gaps and germline variants. 44 % of somatic small variants change representation because they alter germline variants on GRCh38, impacting mutational signatures and kataegis/omikli clusters. Most somatic LINE insertions originate from two hypomethylated non-reference germline LINE insertions, highlighting their impact on insertion mutation burden. These assemblies demonstrate that centromeric, acrocentric, and telomeric regions conventionally excluded from analysis harbor extensive somatic and epigenetic changes. Resolving complete tumor genomes enables a deeper understanding of cancer structural plasticity and the endpoints of breakage-fusion-bridge cycles. These assembled, curated paired normal-tumor benchmarks will serve as a critical foundation for developing future algorithms to characterize the most intractable regions of cancer genomes.

  PublisherDOI

• P385: Long-read genome sequencing determines phasing and methylation status of two de novo variants in PTPN11 in newborn with hypertrophic cardiomyopathy

  Genetics in Medicine Open · 2026-01-01

  articleOpen access

  Given the patient's overgrowth, more comprehensive genome sequencing is pending.Outcome and Follow-Up: The patient will continue to be followed by genetics for annual surveillance.Discussion: Our patient presents with a novel Xq11.2q21.1 duplication.The patient and his cousins are presenting with a neurodevelopmental disorder and short stature in the setting of distinctive facies.Similar duplications of the Xq arm share these features.Martinez et al describes males presenting with identifiable neurodevelopmental disorder, including developmental delay, endocrine axis abnormalities, intellectual disability, absent speech, postnatal growth deficiency, and microcephaly.Additionally, there are reports of brain abnormalities; eye, ear, nose, and oral anomalies; micro/retrognathia; hypoplastic genitalia; cryptorchidism/retractile testes; and digit findings.This family's presentation expands described phenotypes for Xq chromosome duplication syndromes.We suspect increased dosage of duplicated genes mediates the pathogenesis of the identified Xq duplication, including genes involved in nervous system development and function such as NLGN3, OPHN1, GJB1, and EFNB1; the androgen receptor; and transcriptional regulators TAF1 and MED12.The patient's hand and foot overgrowth, which appears to be soft-tissue in nature, is not found in other documented long-arm X chromosome duplications.The overgrowth could be a novel clinical manifestation of Xq duplication syndrome or a second, unidentified genetic condition.Conclusion: This case of three male family members with identical Xq11.2q21.1 duplications expands the phenotype associated with Xq duplications.Exploring genes within the duplication shared with or excluded from other reports can provide insight into genes contributing to clinical presentations.Introduction: Duplications within the long arm of the X chromosome are rare and clinically present in males who inherit the change from a heterozygous mother.With approximately 60 cases reported, clinical features of Xq duplications are not well-characterized.Symptoms vary between individuals due to differences in coordinates or amount of extra genomic material.This makes it challenging to counsel on prognosis.We present a novel Xq12-q13.3duplication in an extended family with clinically asymptomatic mothers.These male patients present with global developmental delay and an autism predisposition.Case Presentation: We present a 14-year-old male with a previously diagnosed Xq11.2q21.1 duplication and a family history of two cousins with the same duplication.His mother's pregnancy was complicated by IUGR (birth at 36 weeks) and he required an NG tube for feeding difficulties.During his first year of life, he had frequent episodes of emesis.Regarding development, he was diagnosed with global developmental delay, given late milestones such as sitting by 1 year of age, walking by 3 years.He experienced regression of first words by 2 years and loss of words at 3 years.He has intellectual disability and attends special education.He also has short stature (138.9 cm, z-score -3.28) with a small pituitary gland and growth hormone deficiency treated by endocrinology.He is managed conservatively for scoliosis and followed by ophthalmology for astigmatism and hypermetropia.Physical examination is remarkable for microcephaly (52.3cm), synophrys, epicanthal folds, hypertelorism, wide nasal bridge, broad nasal tip, smooth philtrum, and low-set ears.Unique from his cousins, the patient's hands and feet appear disproportionately large.X-ray suggests soft tissue enlargement, showing no increased bone growth and estimated bone age within limits for chronological age.Diagnostic Workup: The patient and two cousins were previously evaluated by a geneticist who diagnosed them with chromosome Xq11.2q21.1 duplication syndrome via unspecified genetic testing.

  PublisherOA PDFDOI

• Assessment of nanopore RNA modification calling in human cell lines and synthetic systems

  Genome biology · 2026-05-07

  articleOpen accessSenior author

  BACKGROUND: Nanopore technology enables the direct sequencing of intact RNA molecules allowing for the detection of native chemical modifications. In 2024, Oxford Nanopore Technologies updated direct RNA sequencing from RNA002 to RNA004 platform as well as releasing an improved basecaller (Dorado) capable of de novo detection of eight RNA modifications. We compare RNA002 and RNA004 platforms for poly(A) RNA from GM12878 and HEK293 cell lines and evaluate Dorado-based RNA modification calling. RESULTS: We compute U-to-C mismatches, previously used to identify putative pseudouridine sites, and run m6anet for identifying putative N6-methyladenosine sites. We find that Dorado identifies global and site-specific differences when compared to RNA002 methods. We examine eight RNA modifications detected by Dorado for Nanopore direct RNA sequencing data and propose an analysis strategy for curating RNA modification predictions, including thresholds for read coverage and modification occupancy, canonical RNA-based false positive correction, and comparison with orthogonal information. When comparing modification sites called by Dorado versus those documented by orthogonal datasets, we note significant discordance and we document disagreements between our results and orthogonal datasets. CONCLUSIONS: The transition from RNA002 to RNA004 substantially improves sequencing accuracy and modification calling. However, Nanopore direct RNA sequencing-based RNA modification detection requires careful validation. We recommend combining Nanopore direct RNA sequencing with orthogonal methods and appropriate filtering strategies for increased confidence in modification calls.

  PublisherDOI

• The diploid reference genome of a human embryonic stem cell line

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-30 · 1 citations

  articleOpen access

  Advances in DNA sequencing and assembly technologies are spurring a shift from haploid reference genomes to sample-specific diploid assemblies. Here, we generated the first telomere-to-telomere (T2T) diploid reference for the widely used human embryonic stem cell (hESC) line, H9 (WAe009-A). This haplotype-resolved assembly is highly accurate with comprehensive annotation of genes, segmental duplications, methylation, and chromatin conformation. Pangenomic and phased-locus inference point to H9's mixed ancestry with a predominant European component. H9-specific genomic features include near-perfect telomeres ∼1.65-fold longer than other T2T assemblies, consistent with telomerase activity during pluripotency; chromosome 17 inversions that can predispose offspring to neurological syndromes; and expansions of ncRNA clusters, with overall genomic stability maintained despite extensive culturing. Mapping multi-omic datasets to the genome, we demonstrate the power of this resource for allele-specific, high-precision transcriptomic, genetic, and epigenetic analyses, with far-reaching implications for human development and disease.

  PublisherDOI

• P583: Exploring the unknown: Resolving undiagnosed rare disease cases using long-read genome sequencing and epigenetics

  Genetics in Medicine Open · 2026-01-01

  articleOpen access1st authorCorresponding

  TRIO, XYLT1, YEATS2, ZDHHC14, ZIC2.Repeat expansions and their sequence composition were detected with simultaneous 5-Methylcytosine (5mC) to assess methylation status using tandem repeat genotyping tool and tandem repeat visualizer.Carrier and premutation status were not reported.Results: We identified ~ 2% (7 / 370) of patients tested with LRS harboring a TRD diagnosis.Expansions detected included STARD7 (3), DMPK (2), and one each of DIP2B and RFC1.In addition, an expansion was detected in a compelling gene of uncertain significance, C11ORF80.Methylation analysis revealed that the expansions in DMPK, DIP2B, C11ORF80 were methylated, with pronounced variability in total methylation levels observed across the sample.Methylation levels correlated with the size of the expanded allele, as also observed in carrier parents.There is clear evidence of somatic expansion in blood DNA for all detected expanded alleles, capturing instability and variant origin.Moreover, the diagnosis for TRDs in patients, such as STARD7, DMPK and DIP2B, were clinically actionable for heterozygote parents.Conclusion: Our study demonstrates that LRS serves as a unified platform for clinical testing of TRDs by capturing repeat expansions and the sequence composition simultaneously with 5mC.We observed expansions of various sizes across a subset of genes resulting in a small proportion of diagnoses in this cohort and while also capture an expansion in an emerging disease gene.Although the proportion was modest, the cohort included patients from all subspecialities with diverse phenotypes.Many of these diagnoses would not have been possible without LRS given atypical clinical presentations or lack of available clinical testing for many TRD loci.Thus, our study illustrates the utility of LRS in clinical genetic testing as an effective method for TRD diagnosis.

  PublisherOA PDFDOI

• Multimodal profiling reveals cell type-specific pseudouridine modification and density-dependent translational regulation

  Nucleic Acids Research · 2026-04-08

  articleOpen access

  Pseudouridine (psi) is one of the most abundant mRNA modifications, yet its impact on translation is unclear, in part because existing modification maps are inconsistent, curated comparisons across cell types are lacking, and paired analyses with translation are limited. Using direct RNA nanopore sequencing coupled with our Mod-p ID analytical framework, we mapped psi at single-nucleotide resolution across six immortalized human cell lines. Nanopore sequencing provided single-molecule resolution, enabling quantification of relative modification occupancy and detection of co-occurring modifications. Integrating these psi maps with matched proteomic and ribosome profiling datasets revealed that conserved psi sites installed by the psi synthase TRUB1 are associated with increased protein production. TRUB1 knockout experiments demonstrated a motif-specific reduction in protein abundance, providing direct causal evidence that pseudouridylation enhances protein output. In contrast, transcripts bearing clustered psi sites exhibited reduced protein abundance despite elevated translation efficiency. Controlled in vitro translation experiments confirmed that increasing pseudouridine density within a physiologically relevant range directly reduces protein output, demonstrating a density-dependent effect of pseudouridylation on translation. Together, these findings establish a mechanistic framework in which single-site pseudouridylation enhances protein production, whereas hypermodification impairs translational throughput, revealing pseudouridine density and enzyme specificity as key determinants of proteome output across human cell types.

  PublisherDOI

• Pseudouridylation landscape across 42 <i>S. cerevisiae</i> cytosolic tRNA isoacceptors via Nanopore direct RNA sequencing

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-01

  articleOpen access

  ABSTRACT Pseudouridine is the most abundant RNA base modification due to its prevalence in tRNA and rRNA, where it serves as a key modulator of structure and function. Yet even in a widely used model organism, the budding yeast Saccharomyces cerevisiae , the positions of all pseudouridines in tRNA have not been completely annotated. Using Nanopore direct RNA sequencing (DRS), an established method for detecting RNA pseudouridylation positions, we sequenced cytosolic tRNA from eight pseudouridine synthase (PUS) knockout S. cerevisiae strains, including deletion strains of Pus1, Pus3, and Pus7. Analysis of these data verified thirty-four existing pseudouridine annotations and predicted eleven previously unannotated pseudouridine sites. Our analysis revealed DRS signal changes at several non-uridine sites with the loss of a PUS, including apparent changes in modification abundances at position 37 upon deletion of Pus3. LC-MS/MS and primer extension assays, however, indicated no change in the abundance of these modifications with the loss of Pus3. Our analysis underscores the need for caution in interpreting DRS-based signal changes, particularly in modification-dense regions. Combining existing modification annotations for the thirty-one isoacceptors in the Modomics database with our dataset that added annotations for the remaining eleven isoacceptors, we created a map of all detected pseudouridines, and the enzymes responsible for their catalysis, across the forty-two S. cerevisiae cytosolic tRNA isoacceptors.

  PublisherOA PDFDOI

Frequent coauthors

• Benedict Paten

  61 shared

• Hugh E. Olsen

  University of California, Santa Cruz

  57 shared

• Mark Akeson

  University of California, Santa Cruz

  48 shared

• Adam M. Phillippy

  National Human Genome Research Institute

  39 shared

• Sergey Koren

  National Human Genome Research Institute

  35 shared

• Arang Rhie

  National Human Genome Research Institute

  35 shared

• Evan E. Eichler

  University of Washington

  35 shared

• Justin M. Zook

  National Institute of Standards and Technology

  31 shared

Awards & honors

• 2025 Highly Cited Researchers by Clarivate