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  1. Article: HATCHet2: clone- and haplotype-specific copy number inference from bulk tumor sequencing data.

    Myers, Matthew A / Arnold, Brian J / Bansal, Vineet / Mullen, Katelyn M / Zaccaria, Simone / Raphael, Benjamin J

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Multi-region DNA sequencing of primary tumors and metastases from individual patients helps identify somatic aberrations driving cancer development. However, most methods to infer copy-number aberrations (CNAs) analyze individual samples. We introduce ... ...

    Abstract Multi-region DNA sequencing of primary tumors and metastases from individual patients helps identify somatic aberrations driving cancer development. However, most methods to infer copy-number aberrations (CNAs) analyze individual samples. We introduce HATCHet2 to identify haplotype- and clone-specific CNAs simultaneously from multiple bulk samples. HATCHet2 introduces a novel statistic, the mirrored haplotype B-allele frequency (mhBAF), to identify mirrored-subclonal CNAs having different numbers of copies of parental haplotypes in different tumor clones. HATCHet2 also has high accuracy in identifying focal CNAs and extends the earlier HATCHet method in several directions. We demonstrate HATCHet2's improved accuracy using simulations and a single-cell sequencing dataset. HATCHet2 analysis of 50 prostate cancer samples from 10 patients reveals previously-unreported mirrored-subclonal CNAs affecting cancer genes.
    Language English
    Publishing date 2023-07-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.13.548855
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  2. Article ; Online: Identifying tumor clones in sparse single-cell mutation data.

    Myers, Matthew A / Zaccaria, Simone / Raphael, Benjamin J

    Bioinformatics (Oxford, England)

    2020  Volume 36, Issue Suppl_1, Page(s) i186–i193

    Abstract: Motivation: Recent single-cell DNA sequencing technologies enable whole-genome sequencing of hundreds to thousands of individual cells. However, these technologies have ultra-low sequencing coverage (<0.5× per cell) which has limited their use to the ... ...

    Abstract Motivation: Recent single-cell DNA sequencing technologies enable whole-genome sequencing of hundreds to thousands of individual cells. However, these technologies have ultra-low sequencing coverage (<0.5× per cell) which has limited their use to the analysis of large copy-number aberrations (CNAs) in individual cells. While CNAs are useful markers in cancer studies, single-nucleotide mutations are equally important, both in cancer studies and in other applications. However, ultra-low coverage sequencing yields single-nucleotide mutation data that are too sparse for current single-cell analysis methods.
    Results: We introduce SBMClone, a method to infer clusters of cells, or clones, that share groups of somatic single-nucleotide mutations. SBMClone uses a stochastic block model to overcome sparsity in ultra-low coverage single-cell sequencing data, and we show that SBMClone accurately infers the true clonal composition on simulated datasets with coverage at low as 0.2×. We applied SBMClone to single-cell whole-genome sequencing data from two breast cancer patients obtained using two different sequencing technologies. On the first patient, sequenced using the 10X Genomics CNV solution with sequencing coverage ≈0.03×, SBMClone recovers the major clonal composition when incorporating a small amount of additional information. On the second patient, where pre- and post-treatment tumor samples were sequenced using DOP-PCR with sequencing coverage ≈0.5×, SBMClone shows that tumor cells are present in the post-treatment sample, contrary to published analysis of this dataset.
    Availability and implementation: SBMClone is available on the GitHub repository https://github.com/raphael-group/SBMClone.
    Supplementary information: Supplementary data are available at Bioinformatics online.
    MeSH term(s) Algorithms ; Clone Cells ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Software ; Whole Genome Sequencing
    Language English
    Publishing date 2020-07-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 1422668-6
    ISSN 1367-4811 ; 1367-4803
    ISSN (online) 1367-4811
    ISSN 1367-4803
    DOI 10.1093/bioinformatics/btaa449
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  3. Article ; Online: CALDER: Inferring Phylogenetic Trees from Longitudinal Tumor Samples.

    Myers, Matthew A / Satas, Gryte / Raphael, Benjamin J

    Cell systems

    2019  Volume 8, Issue 6, Page(s) 514–522.e5

    Abstract: Longitudinal DNA sequencing of cancer patients yields insight into how tumors evolve over time or in response to treatment. However, sequencing data from bulk tumor samples often have considerable ambiguity in clonal composition, complicating the ... ...

    Abstract Longitudinal DNA sequencing of cancer patients yields insight into how tumors evolve over time or in response to treatment. However, sequencing data from bulk tumor samples often have considerable ambiguity in clonal composition, complicating the inference of ancestral relationships between clones. We introduce Cancer Analysis of Longitudinal Data through Evolutionary Reconstruction (CALDER), an algorithm to infer phylogenetic trees from longitudinal bulk DNA sequencing data. CALDER explicitly models a longitudinally observed phylogeny incorporating constraints that longitudinal sampling imposes on phylogeny reconstruction. We show on simulated bulk tumor data that longitudinal constraints substantially reduce ambiguity in phylogeny reconstruction and that CALDER outperforms existing methods that do not leverage this longitudinal information. On real data from two chronic lymphocytic leukemia patients, we find that CALDER reconstructs more plausible and parsimonious phylogenies than existing methods, with CALDER phylogenies containing fewer tumor clones per sample. CALDER's use of longitudinal information will be advantageous in further studies of tumor heterogeneity and evolution.
    MeSH term(s) Algorithms ; Base Sequence ; Cell Lineage ; Computational Biology/methods ; Computer Simulation ; DNA, Neoplasm ; Data Analysis ; Humans ; Leukemia, Lymphoid/genetics ; Neoplasms/genetics ; Phylogeny ; Software
    Chemical Substances DNA, Neoplasm
    Language English
    Publishing date 2019-06-19
    Publishing country United States
    Document type Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2854138-8
    ISSN 2405-4720 ; 2405-4712
    ISSN (online) 2405-4720
    ISSN 2405-4712
    DOI 10.1016/j.cels.2019.05.010
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  4. Article ; Online: Multiple-Choice versus Open-Ended Questions in Advanced Clinical Neuroanatomy: Using a National Neuroanatomy Assessment to Investigate Variability in Performance Using Different Question Types.

    Merzougui, Wassim H / Myers, Matthew A / Hall, Samuel / Elmansouri, Ahmad / Parker, Rob / Robson, Alistair D / Kurn, Octavia / Parrott, Rachel / Geoghegan, Kate / Harrison, Charlotte H / Anbu, Deepika / Dean, Oliver / Border, Scott

    Anatomical sciences education

    2021  Volume 14, Issue 3, Page(s) 296–305

    Abstract: Methods of assessment in anatomy vary across medical schools in the United Kingdom (UK) and beyond; common methods include written, spotter, and oral assessment. However, there is limited research evaluating these methods in regards to student ... ...

    Abstract Methods of assessment in anatomy vary across medical schools in the United Kingdom (UK) and beyond; common methods include written, spotter, and oral assessment. However, there is limited research evaluating these methods in regards to student performance and perception. The National Undergraduate Neuroanatomy Competition (NUNC) is held annually for medical students throughout the UK. Prior to 2017, the competition asked open-ended questions (OEQ) in the anatomy spotter examination, and in subsequent years also asked single best answer (SBA) questions. The aim of this study is to assess medical students' performance on, and perception of, SBA and OEQ methods of assessment in a spotter style anatomy examination. Student examination performance was compared between OEQ (2013-2016) and SBA (2017-2020) for overall score and each neuroanatomical subtopic. Additionally, a questionnaire explored students' perceptions of SBAs. A total of 631 students attended the NUNC in the studied period. The average mark was significantly higher in SBAs compared to OEQs (60.6% vs. 43.1%, P < 0.0001)-this was true for all neuroanatomical subtopics except the cerebellum. Students felt that they performed better on SBA than OEQs, and diencephalon was felt to be the most difficult neuroanatomical subtopic (n = 38, 34.8%). Students perceived SBA questions to be easier than OEQs and performed significantly better on them in a neuroanatomical spotter examination. Further work is needed to ascertain whether this result is replicable throughout anatomy education.
    MeSH term(s) Anatomy/education ; Curriculum ; Education, Medical, Undergraduate ; Educational Measurement ; Humans ; Neuroanatomy/education ; Schools, Medical ; Students, Medical ; Surveys and Questionnaires
    Language English
    Publishing date 2021-02-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2483491-9
    ISSN 1935-9780 ; 1935-9772
    ISSN (online) 1935-9780
    ISSN 1935-9772
    DOI 10.1002/ase.2053
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    Zs.A 6787: Show issues Location:
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  5. Article ; Online: Spinal fractures incurred by a fall from standing height.

    Hall, Samuel / Myers, Matthew A / Sadek, Ahmed-Ramadan / Baxter, Mark / Griffith, Colin / Dare, Christopher / Shenouda, Emad / Nader-Sepahi, Ali

    Clinical neurology and neurosurgery

    2019  Volume 177, Page(s) 106–113

    Abstract: Objective: Falls from standing are common, particularly amongst the aging population, due to declining mobility, proprioception and vision. They are often complicated by fragility fractures, including vertebral fractures, that are associated with ... ...

    Abstract Objective: Falls from standing are common, particularly amongst the aging population, due to declining mobility, proprioception and vision. They are often complicated by fragility fractures, including vertebral fractures, that are associated with significant morbidity and may represent a pre-terminal condition with high one-year mortality rates.
    Patients and methods: A retrospective review of the Trauma Audit and Research Network database for a major trauma centre was conducted for all patients admitted between January 2011 and December 2016. Patients with a spinal fracture and a confirmed fall from standing height were eligible for inclusion. Case notes were reviewed for demographics, Injury Severity Score, Charlson co-morbidity score, treatment, complications and outcomes.
    Results: Of 1408 patients with a spine fracture admitted during the study period, 229 (16.3%) were confirmed to be secondary to a fall from standing height. The average age of this cohort was 76.6 ± 14.5 years and 134 (58.5%) cases were female. The average ISS score was 9.7 ± 5.4. The 229 patients sustained 283 fractures with a distribution of: cervical (n = 140), thoracic (n = 65) and lumbar (n = 78) spine. Fifty-six (24.5%) patients underwent surgical intervention. Forty-three patients (18.7%) died within 6 months of admission and all-cause mortality was significantly higher in patients with increasing age and Charlson co-morbidity score.
    Conclusion: Spinal fractures due to a fall from standing height represent one sixth of the fracture workload of the emergency spinal service at a major trauma centre. Whilst the majority of patients can be managed conservatively there are still considerable implications for hospital bed usage and patient mortality.
    MeSH term(s) Accidental Falls/statistics & numerical data ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cervical Vertebrae/injuries ; Cervical Vertebrae/surgery ; Cohort Studies ; Female ; Hospitalization/statistics & numerical data ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Spinal Cord Injuries/complications ; Spinal Cord Injuries/surgery ; Spinal Fractures/epidemiology ; Spinal Fractures/surgery ; Trauma Centers/statistics & numerical data
    Language English
    Publishing date 2019-01-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 193107-6
    ISSN 1872-6968 ; 0303-8467
    ISSN (online) 1872-6968
    ISSN 0303-8467
    DOI 10.1016/j.clineuro.2019.01.005
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  6. Article ; Online: The Efficacy of Frontline Near-Peer Teaching in a Modern Medical Curriculum.

    Harrison, Charlotte H / Elmansouri, Ahmad / Parton, William / Myers, Matthew A / Hall, Samuel / Stephens, Jonny R / Seaby, Eleanor G / Border, Scott

    Anatomical sciences education

    2018  Volume 12, Issue 3, Page(s) 236–244

    Abstract: Within medical education a reduction in curriculum time for subjects, such as anatomy puts pressure on educators to ensure the same learning outcomes are conveyed in less time. This has the potential to impact negatively on student experience. Near-peer ... ...

    Abstract Within medical education a reduction in curriculum time for subjects, such as anatomy puts pressure on educators to ensure the same learning outcomes are conveyed in less time. This has the potential to impact negatively on student experience. Near-peer teaching (NPT) is often praised as an effective revision tool, but its use as a frontline teaching resource remains unreported. The study explores the potential for NPT to promote delivery of learning outcomes and maximize student experience within a neuroanatomy module for second year medical students. The study occurred in three educational settings, (1) frontline NPT of cranial nerves, (2) revision session NPT of cranial nerves, and (3) NPT alongside faculty staff in laboratory-based neuroanatomy practical exercises. For the first and second components, knowledge was measured using a pre- and post-session test and student perception was ascertained with a questionnaire. For the third component, student perception was assessed with an end-of-module survey. The results show that overall, NPT was well received by learners. A significant knowledge gain was seen between the pre- and post-session test of the frontline NPT session. The study presents evidence in favor of using NPTs to supplement the delivery of learning outcomes in a time and resource constrained curriculum. In particular, for the effective delivery of frontline material. Anat Sci Educ 0: 1-9. © 2018 American Association of Anatomists.
    MeSH term(s) Anatomy/education ; Cross-Sectional Studies ; Curriculum/statistics & numerical data ; Curriculum/trends ; Education, Medical, Undergraduate/methods ; Education, Medical, Undergraduate/organization & administration ; Education, Medical, Undergraduate/trends ; Educational Measurement ; Humans ; Learning ; Peer Group ; Program Evaluation ; Schools, Medical/organization & administration ; Schools, Medical/statistics & numerical data ; Schools, Medical/trends ; Students, Medical/statistics & numerical data ; Teaching/organization & administration ; Teaching/trends
    Language English
    Publishing date 2018-10-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2483491-9
    ISSN 1935-9780 ; 1935-9772
    ISSN (online) 1935-9780
    ISSN 1935-9772
    DOI 10.1002/ase.1827
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  7. Article ; Online: The Wessex modified Richmond Sedation Scale as a novel tool for monitoring patients at risk of malignant MCA syndrome.

    Hayat, Tayyib T A / Myers, Matthew A / Hell, John / Cordingly, Matthew / Bulters, Diederik O / Weir, Nicolas / Pengas, George

    Acta neurochirurgica

    2018  Volume 160, Issue 6, Page(s) 1115–1119

    Abstract: Background: The Wessex Modified Richmond Sedation Scale (WMRSS) has been developed with the aim of improving the early identification of patients requiring decompressive hemicraniectomy for malignant middle cerebral artery syndrome (MMS). The objective ... ...

    Abstract Background: The Wessex Modified Richmond Sedation Scale (WMRSS) has been developed with the aim of improving the early identification of patients requiring decompressive hemicraniectomy for malignant middle cerebral artery syndrome (MMS). The objective of this study was to evaluate the WMRSS against the Glasgow Coma Scale (GCS).
    Methods: A retrospective study was conducted of patients admitted to our unit for observation of MMS. Data were obtained on WMRSS and GCS recordings from admission up to 120-h post-ictus. Patients' meeting inclusion criteria were recommended for theatre based on subsequent deteriorations in consciousness on either WMRSS or GCS from a 6-h post-stroke baseline, after ruling out non-neurological causes.
    Results: Approximately, 60% of those eligible for monitoring were not recommended for theatre, and none died; however, these patients continued to demonstrate some variability in recorded conscious level. Patients requiring surgical intervention showed earlier drops in WMRSS compared to GCS. Neither the GCS nor the WMRSS on admission predicted the subsequent need for decompressive surgery. There was no increase in mortality with the introduction of WMRSS.
    Conclusions: WMRSS adds value to monitoring MMS by indicating need for surgery prior to GCS. Early reduction in consciousness may not be sufficient for proceeding to surgical intervention, but subsequent reduction in consciousness may be a more appropriate criterion for surgery.
    MeSH term(s) Adult ; Aged ; Consciousness ; Decompression, Surgical ; Female ; Glasgow Coma Scale ; Humans ; Infarction, Middle Cerebral Artery/pathology ; Infarction, Middle Cerebral Artery/surgery ; Male ; Middle Aged ; Monitoring, Physiologic/methods
    Language English
    Publishing date 2018-04-11
    Publishing country Austria
    Document type Comparative Study ; Journal Article
    ZDB-ID 80010-7
    ISSN 0942-0940 ; 0001-6268
    ISSN (online) 0942-0940
    ISSN 0001-6268
    DOI 10.1007/s00701-018-3531-y
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  8. Article ; Online: The Career Impact of the National Undergraduate Neuroanatomy Competition.

    Hall, Samuel / Stephens, Jonny R / Myers, Matthew A / Elmansouri, Ahmad / Geoghegan, Kate / Harrison, Charlotte H / Nagy, Eva / Anbu, Deepika / Parton, William J C / Payne, December R / Seaby, Eleanor / Border, Scott

    World neurosurgery

    2019  Volume 133, Page(s) e535–e539

    Abstract: Background: Neurosurgery is a notoriously difficult career to enter and requires medical students to engage in extracurricular activities to demonstrate their commitment to the specialty. The National Undergraduate Neuroanatomy Competition (NUNC) was ... ...

    Abstract Background: Neurosurgery is a notoriously difficult career to enter and requires medical students to engage in extracurricular activities to demonstrate their commitment to the specialty. The National Undergraduate Neuroanatomy Competition (NUNC) was established in 2013 as a means for students to display this commitment as well as academic ability.
    Methods: A bespoke 22-item questionnaire was designed to determine career outcomes and the role of competition attendance in job applications. It was distributed using the SurveyMonkey website to the 87 attendees at the 2013 and 2014 competitions.
    Results: Responses were received by 40 competitors (response rate, 46.0%). Twenty-four responders (60.0%) intended to pursue a career in either neurosurgery (n = 18) or neurology (n = 6). This included 10 responders (25.0%) who had successfully entered either neurosurgery (n = 9) or neurology (n = 1). The performance of these 10 was significantly better than the other responders (57.0 ± 13.6% vs. 46.5 ± 13.5% [n = 30]; P = 0.036). Seventeen responders (42.5%) either included their attendance at NUNC in a post-Foundation job application or intend to.
    Conclusions: The NUNC provides the opportunity for medical students to demonstrate their interest in neurosurgery. It has the potential to be used as a tool for recognizing medical students suitable for neurosurgery training.
    MeSH term(s) Awards and Prizes ; Career Choice ; Humans ; Neuroanatomy ; Neurosurgery ; Professional Competence ; Students, Medical
    Language English
    Publishing date 2019-09-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2534351-8
    ISSN 1878-8769 ; 1878-8750
    ISSN (online) 1878-8769
    ISSN 1878-8750
    DOI 10.1016/j.wneu.2019.09.086
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  9. Article ; Online: The benefits of being a near-peer teacher.

    Hall, Samuel / Harrison, Charlotte H / Stephens, Jonny / Andrade, Matheus Gesteria / Seaby, Eleanor G / Parton, William / McElligott, Simon / Myers, Matthew A / Elmansouri, Ahmed / Ahn, Michael / Parrott, Rachel / Smith, Claire F / Border, Scott

    The clinical teacher

    2018  Volume 15, Issue 5, Page(s) 403–407

    Abstract: Background: Near-peer teaching is used in anatomy education because of its benefits to the learner, teacher and faculty members. Despite the range of reports focusing on the learner, the advantages for the teacher, which are thought to include ... ...

    Abstract Background: Near-peer teaching is used in anatomy education because of its benefits to the learner, teacher and faculty members. Despite the range of reports focusing on the learner, the advantages for the teacher, which are thought to include communication skills, subject knowledge and employability, are only beginning to be explored.
    Method: A questionnaire was distributed to the teachers involved in anatomy near-peer teaching at the University of Southampton and Brighton and Sussex Medical School (BSMS). This questionnaire was designed using a rating scale of 0-10 to assess teacher perspectives on their level of knowledge, teaching skills and enjoyment of teaching. Free-text responses determined the teachers' motivation and perceived benefits from the teaching.
    Results: Twenty-eight questionnaires were gathered (54.9% response rate), including 20 from Southampton and eight from BSMS. Long-term knowledge retention and better understanding of the material were rated 8.1 and 7.9 out of 10, respectively. Eight responses were from currently practising doctors, who rated how much they now use their teaching skills as doctors as 8.9 out of 10. Of the eight doctors, seven gained points for their foundation programme applications as a direct result of near-peer teaching. The most common motivator for engaging in teaching was to improve subject matter knowledge and the most common benefit was improved communication skills. There are numerous advantages to being a near-peer teacher in medical school DISCUSSION: There are numerous advantages to being a near-peer teacher in medical school, which include knowledge improvement, transferrable professional skills and employability. These initial results support the hypothesised benefits to the teachers and provide a foundation for further longitudinal studies.
    MeSH term(s) Clinical Competence ; Communication ; Curriculum ; Education, Medical, Undergraduate/methods ; Humans ; Knowledge ; Motivation ; Peer Group ; Students, Medical/psychology ; Teaching/organization & administration ; Teaching/standards ; United Kingdom
    Language English
    Publishing date 2018-03-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2151518-9
    ISSN 1743-498X ; 1743-4971
    ISSN (online) 1743-498X
    ISSN 1743-4971
    DOI 10.1111/tct.12784
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  10. Article ; Online: The National Undergraduate Neuroanatomy Competition: Lessons Learned from Partnering with Students to Innovate Undergraduate Neuroanatomy Education.

    Geoghegan, Kate / Payne, December R / Myers, Matthew A / Hall, Samuel / Elmansouri, Ahmad / Parton, William J C / Harrison, Charlotte H / Stephens, Jonny / Parker, Rob / Rae, Shivani / Merzougui, Wassim / Nagy, Eva / Venkatesh, Prarthana / Parrott, Rachel / Border, Scott

    The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry

    2018  Volume 25, Issue 3, Page(s) 271–280

    Abstract: Undergraduates often perceive neuroscience to be a challenging discipline. As the scope of neuroscience continues to expand, it is important to provide undergraduates with sufficient opportunities to develop their knowledge and skills with the aim of ... ...

    Abstract Undergraduates often perceive neuroscience to be a challenging discipline. As the scope of neuroscience continues to expand, it is important to provide undergraduates with sufficient opportunities to develop their knowledge and skills with the aim of encouraging the future generation of basic and clinical neuroscientists. Through our experience of developing the National Undergraduate Neuroanatomy Competition (NUNC), we have accrued an extensive volume of performance data and subjective insight into the delivery of undergraduate neuroanatomy education, which has the potential to inform how to better engage students within this field. More broadly, our group has implemented a technology enhanced learning platform alongside a peer-assisted teaching program. These achieve the dual purpose of compensating for the reduction in dedicated neuroanatomy teaching hours and encouraging undergraduates to develop an interest in the neurosciences. Here, we consider how improving the learning experience at an undergraduate level encourages further engagement in the neurosciences and the importance of this within the wider neuroscience community.
    MeSH term(s) Education, Distance ; Education, Medical, Undergraduate/methods ; Humans ; Neuroanatomy/education ; Students ; Teaching/trends ; United Kingdom ; Universities
    Language English
    Publishing date 2018-07-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1233753-5
    ISSN 1089-4098 ; 1073-8584
    ISSN (online) 1089-4098
    ISSN 1073-8584
    DOI 10.1177/1073858418788000
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