Biomedical subjects

James T Robinson

Publications and source records attributed to James T Robinson.

6 recordsLinked to original sources

PubMed2026

Clinical Variant Interpretation with the Integrative Genomics Viewer (IGV) for Molecular Pathologists.

The integrative genomics viewer (IGV) is a pivotal tool in clinical genomics, enabling the visualization and interpretation of complex sequencing data. Bringing clinical knowledge to bear with visual evaluation of sequencing results is the primary means by which molecular pathologists and other professionals assess and finalize cases. A variety of software tools can assist, but their relationship to the underlying data must be understood and applied systematically. This study includes essential background on next-generation sequencing (NGS) data file types (e.g., FASTQ, BAM, VCF) with a discussion of their format and purpose. We then describe features of IGV that derive nuances from these files. We utilize a series of curated practical cases based on clinical vignettes through which the reader will interact with clinical NGS sequencing data using the IGV software to review various types of clinically relevant variants relative to the human reference genome. These clinical vignettes have been curated to describe examples of some of the complexities of interpretation of genomic data, and how utilizing IGV as part of a routine workflow can provide additional interpretive information for variants beyond routine bioinformatic software algorithm variant calls. The visual inspection of genomic variants utilizing the tools within IGV can unmask subtle contextual cues (i.e., variant allele frequency, strand bias, tissue-specific context) that can influence the interpretation of genomic variants. Although this study focuses on using IGV for the detection and interpretation of somatic variants, the provided applications can be extrapolated for use in the germline setting, including analysis of complex variants and detection of mosaicism.

Humans↗

PubMed2026

igv-reports: embedding interactive genomic visualizations in HTML reports to aid variant review.

SUMMARY: We present igv-reports, a command-line tool to create standalone HTML pages embedding interactive genomic visualizations of read alignments and associated annotations to support variant inspection workflows. The reports contain all data and code required for visualization of the variant sites, with no dependencies on the input data files. AVAILABILITY AND IMPLEMENTATION: igv-reports is a command-line application written in Python. It is freely available at https://github.com/igvteam/igv-reports under an MIT license.

Software↗

PubMed2023

3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma.

Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups of ependymoma are the supratentorial ZFTA-fusion associated and the posterior fossa ependymoma group A. In both groups, tumors occur mainly in young children and frequently recur after treatment. Although molecular mechanisms underlying these diseases have recently been uncovered, they remain difficult to target and innovative therapeutic approaches are urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C), complemented with CTCF and H3K27ac ChIP-seq, as well as gene expression and DNA methylation analysis in primary and relapsed ependymoma tumors, to identify chromosomal conformations and regulatory mechanisms associated with aberrant gene expression. In particular, we observe the formation of new topologically associating domains ('neo-TADs') caused by structural variants, group-specific 3D chromatin loops, and the replacement of CTCF insulators by DNA hyper-methylation. Through inhibition experiments, we validate that genes implicated by these 3D genome conformations are essential for the survival of patient-derived ependymoma models in a group-specific manner. Thus, this study extends our ability to reveal tumor-dependency genes by 3D genome conformations even in tumors that lack targetable genetic alterations.

Child↗

PubMed2006

Negative pressure wound therapy to treat hematomas and surgical incisions following high-energy trauma.

PURPOSE: To evaluate the use of negative pressure wound therapy (NPWT) to augment healing of surgical incisions and hematomas after high-energy trauma. MATERIALS: This study is a prospective randomized evaluation of NPWT in trauma patients, randomizing patients with draining hematomas to either a pressure dressing (group A) or a VAC (group B). Additionally, patients with calcaneus, pilon, and high-energy tibial plateau fractures were randomized to either a standard postoperative dressing or a VAC over the sutures. RESULTS: There were 44 patients randomized into the hematoma study. Group A drained a mean of 3.1 days, compared with only 1.6 days for group B. This difference was significant (p=0.03). The infection rate for group A was 16%, compared with 8% in group B. An additional 44 patients have been randomized into the fracture study. Again, a significant difference (p=0.02) was present when comparing drainage in group A (4.8 days) and group B (1.8 days). No significant difference was present at current enrollment for infection or wound breakdown. DISCUSSION: NPWT has been used on many complex traumatic wounds. Potential mechanisms of action include angiogenesis, increased blood flow, and decreased interstitial fluid. This ongoing randomized study has demonstrated decreased drainage and improved wound healing following both hematomas and severe fractures.

Adult↗

PubMed2005

Reconstruction of the posterolateral corner of the knee.

PURPOSE: To describe a technique for reconstruction of the posterolateral corner (PLC) of the knee and report the results of a prospective series of patients. TYPE OF STUDY: Case series. METHODS: Twenty-two patients with PLC injuries underwent reconstruction; 15 patients had multiligamentous knee injuries and 7 had isolated PLC injuries. We used the modified 2-tailed technique that reconstructs the popliteofibular ligament and fibulocollateral ligament. The technique includes use of an allograft tendon placed through transtibial and transfibular bone tunnels and around a screw on the lateral femoral condyle. All patients have been followed-up prospectively with clinical examinations, Lysholm knee scores, KT-2000 ligament arthrometer examinations, and evaluation of work and recreational functional status. RESULTS: There were 15 male and 7 female patients (mean age, 32 years; range, 17 to 55 years). Follow-up was a minimum of 24 months (mean, 29.5 months; range, 24 to 38 months). Mean range of motion is extension of 0.2 degrees (range, 0 degrees to 5 degrees) and flexion of 133.4 degrees (80 degrees to 144 degrees). The range of motion for the multiligamentous knees was 0.3 degrees to 129 degrees compared with 0 degrees to 143 degrees for knees with isolated corner injuries. Mean Lysholm knee scores were 90 for the entire group with a score of 92 for the multiligamentous knees and 88 for the isolated corners. Stability was clinically graded on a scale of 0 to 3 for both varus stress and external rotation, with a score of 2 or 3 indicating a failed PLC reconstruction. The mean score for varus stress was 0.2 for the whole group, with 0.3 in the multiligamentous knee and 0.1 for the isolated injuries. Similarly, the mean score for external rotation was 0.4, with a 0.5 for multiligamentous knee and 0.3 for isolated PLC injuries. There were 2 failures in the multiligamentous knee injury group (13%), compared with no failures in the isolated PLC group. The failure rate for the whole study was 9%. CONCLUSIONS: Reconstruction of the PLC using an allograft reconstruction of the popliteus, popliteofibular, and fibulocollateral ligaments yielded a stable reconstruction with excellent functional results. Predictably, range of motion and incidence of failure were both better for patients with isolated PLC injuries than for those with multiligamentous knees. Both groups, however, showed excellent overall functional results. LEVEL OF EVIDENCE: Level IV, case series.

Adolescent↗

PubMed2004

Vascular injuries in knee dislocations: the role of physical examination in determining the need for arteriography.

BACKGROUND: Popliteal artery injury is frequently associated with knee dislocation following blunt trauma, an injury that is being seen with increasing frequency. The primary purpose of the present study was to evaluate the use of physical examination to determine the need for arteriography in a large series of patients with knee dislocation. The secondary purpose was to evaluate the correlation between physical examination findings and clinically important vascular injury in the subgroup of patients who underwent arteriography. METHODS: One hundred and thirty consecutive patients (138 knees) who had sustained an acute multiligamentous knee injury were evaluated at our level-1 trauma center between August 1996 and May 2002 and were included in a prospective outcome study. Four patients (four knees) were lost to follow-up, leaving 126 patients (134 knees) available for inclusion in the study. The results of the physical examination of the vascular status of the extremities were used to determine the need for arteriography. The mean duration of follow-up was nineteen months (range, eight to forty-eight months). Physical examination findings, magnetic resonance imaging findings, and surgical findings were combined to determine the extent of ligamentous damage. RESULTS: Nine patients had flow-limiting popliteal artery damage, for an overall prevalence of 7%. Ten patients had abnormal findings on physical examination, with one patient having a false-positive result and nine having a true-positive result. The knee dislocations in the nine patients with popliteal artery damage were classified, according to the Wascher modification of the Schenck system, as KD-III (one knee), KD-IV (seven knees), and KD-V (one knee). CONCLUSIONS: Selective arteriography based on serial physical examinations is a safe and prudent policy following knee dislocation. There is a strong correlation between the results of physical examination and the need for arteriography. Increased vigilance may be justified in the case of a patient with a KD-IV dislocation, for whom serial examinations should continue for at least forty-eight hours.

Adolescent↗