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PubMed2025

CREMSA: compressed indexing of (ultra) large multiple sequence alignments.

MOTIVATION: Recent viral outbreaks motivate the systematic collection of pathogenic genomes in order to accelerate their study and monitor the apparition/spread of variants. Due to their limited length and temporal proximity of their sequencing, viral genomes are usually organized, and analyzed as oversized Multiple Sequence Alignments (MSAs). Such MSAs are largely ungapped, and mostly homogeneous on a column-wise level but not at a sequential level due to local variations, hindering the performances of sequential compression algorithms. RESULTS: In order to enable an efficient handling of MSAs, including subsequent statistical analyses, we introduce CREMSA (Column-wise Run-length Encoding for MSAs), a new index that builds on sparse bitvector representations to compress an existing or streamed MSA, all the while allowing for an expressive set of accelerated requests to query the alignment without prior decompression. Using CREMSA, a 65 GB MSA consisting of 1.9M SARS-CoV 2 genomes could be compressed into 22 MB using less than half a gigabyte of main memory, while executing access requests in the order of 100 ns. Such a speed up enables a comprehensive analysis of covariation over this very large MSA. We further assess the impact of the sequence ordering on the compressibility of MSAs and propose a resorting strategy that, despite the proven NP-hardness of an optimal sort, induces greatly increased compression ratios at a marginal computational cost. AVAILABILITY AND IMPLEMENTATION: CREMSA is freely accessible at https://gitlab.univ-lille.fr/cremsa/cremsa. The Snakemake workflow for the benchmarks is available at: https://gitlab.univ-lille.fr/cremsa/bench. The data used in the paper is on Zenodo at https://zenodo.org/records/14698859 and https://zenodo.org/records/15100011.

SARS-CoV-2↗

PubMed2026

STABIX: summary-statistic-based GWAS indexing and compression.

MOTIVATION: Genome-wide association studies (GWAS) are widely used to investigate the role of genetics in disease traits, but the resulting file sizes from these studies are large, posing barriers to efficient storage, sharing, and querying. This issue is especially important for biobanks like the UK Biobank that publish GWAS for thousands of traits, increasing the volume of data that must be effectively managed. Current compression and query methods reduce file sizes and allow for quick genomic position-based queries but do not provide utility for quickly finding loci based on their summary statistics. For example, finding all SNVs in a particular p-value range would require decompressing and scanning the whole file. We propose a new tool, STABIX, which introduces summary-statistic-based queries and improves upon the standard bgzip compression and Tabix query tool in both compression ratio and decompression speed. RESULTS: When applied to 10 GWAS files from PanUKBB, STABIX created smaller compressed data and indices than Tabix for all files, where bgzip and tbi files were an average of 1.2 times the size of STABIX compressed files and indexes. In the same 10 files, STABIX per gene decompression was, on average 7× faster than Tabix per gene decompression, and achieved faster per gene decompression times for over 99% of nearly 20,000 genes. AVAILABILITY AND IMPLEMENTATION: Software freely available for download at GitHub: https://github.com/kristen-schneider/stabix/.

Genome-Wide Association Study↗

PubMed2026

RLBWT-based LCP computation in compressed space for terabase-scale pangenome analysis.

MOTIVATION: Lossless full text indexes are utilized in a myriad of applications in bioinformatics. The continuously decreasing cost of generating biological data has resulted in the need to build full text indexes on biological datasets of increasing size. Many compressed full text indexes have been developed to address this problem. In particular, run-length Burrows-Wheeler transform (RLBWT) based compressed full text indexes have seen wide development and adoption. However, the construction of these RLBWT-based compressed full text indexes is still computationally expensive, sometimes prohibitively so, even for current dataset sizes. RESULTS: Therefore, we present algorithms for the construction of RLBWT-based compressed full text indexes and their supporting data structures in compressed space. The algorithms have a space complexity of O(r) words and run in O(n) time for repetitive datasets, where r is the number of runs in the BWT, n is the length of the text, and repetitive datasets implies nr∈Ω(log n). We provide the first algorithm to compute LCP-related information for repetitive datasets in optimal time and O(r) space, greatly reducing memory requirements. The key idea behind this algorithm is the utilization of r samples of the inverse suffix array at regular intervals. For example, on the Human Pangenome Reference Consortium Release 2 dataset, this reduces peak memory from 2135 GiB to 170 GiB (12.6x reduction) compared to the previous best method (pfp-thresholds). AVAILABILITY AND IMPLEMENTATION: The implementation is available at https://github.com/ucfcbb/TeraTools.

Algorithms↗

PubMed1991

Chronic nerve compression model for the double crush hypothesis.

"Double crush hypothesis" is a phrase that has entered clinical use based on a hypothesis presented by Upton and McComas in 1973. Although clinical examples of the double crush are appearing more frequently, there has been no experimental proof of this hypothesis as it relates to chronic nerve compression. This study used a model of sciatic nerve minimal banding in the rat to investigate the effect on electrophysiological function of single or double band placement, concurrently or separated in time. This study confirms that the existence of two sites of simultaneous compression, or a second (later) site of compression, placed either proximal or distal to the first (earlier) site of compression, will result in significantly poorer neural function than will a single site of compression.

Action Potentials↗

PubMed1996

Effects of deferoxamine on ischemia/reperfusion injury after peripheral nerve compression.

We have demonstrated previously that acute nerve compression produces ischemia/reperfusion injury in rat sciatic nerve. In this study, we evaluated the effects of deferoxamine, an antioxidant, on recovery from ischemia/reperfusion injury after nerve compression. The sciatic nerves of male Sprague-Dawley rats, 370 to 430 g, were subjected to 24 hours of compression with Silastic tubing. The control group received intravenous saline solution at the time of decompression. The therapeutic group received intravenous deferoxamine (50 mg per kilogram) at the time of removal of the Silastic tubing. Nerve tissues within and distal to the compression site were assayed for malondialdehyde (MDA) levels and for growth-associated protein 43 (GAP-43) expression, as markers of ischemia/reperfusion injury and nerve regeneration, respectively. In the control group (injury alone), the MDA levels were three times higher than normal during the initial 10 days and returned to normal by 14 days. In contrast, the deferoxamine treatment group had MDA levels that were not significantly different from precompression levels. In the control group, enhanced GAP-43 expression persisted until late in the recovery period. In the deferoxamine treatment group, the increased GAP-43 expression subsided early. The results suggest that the treatment of compressed peripheral nerve with deferoxamine at the time of surgical decompression reduces ischemia/reperfusion injury.

Animals↗

PubMed2001

C-terminal flanking peptide of neuropeptide Y in DRG following nerve compression.

The C-terminal flanking peptide of neuropeptide Y (CPON) was studied in dorsal root ganglia (DRG) by immunocytochemistry after different recovery periods (3, 6,14 and 28 days) following tourniquet compression of the rat hindlimb (sciatic nerve; 150 or 300 mmHg; 2 h). Compression induced a transient increase in the number of CPON-positive DRG-neurons (the contralateral uninjured side was devoid of CPON-positive cells). The compression-induced increase in CPON was less than that observed in separate rats subjected to sciatic nerve transection. The results show that compression induces regenerative changes in peripheral neurons and that such an injury of the nerve trunk is not limited to the site of the compression but results in the activation of the entire neuron.

Animals↗

PubMedDate not supplied

Functional abnormalities of the cervical cord and lower medulla and their effect on pain: observations in chronic pain patients with incidental mild Chiari I malformation and moderate to severe cervical cord compression.

OBJECTIVE: Abnormalities of central sensory processing may play a role in the pathogenesis of chronic pain. The Chiari I malformation is a congenital hindbrain anomaly characterized by protrusion of the cerebellar tonsils into the upper cervical canal, with variable effects on the lower brain stem and cervical cord. The purpose of this study was to compare sensory function and pain among patients with chronic pain who had these disorders incidentally diagnosed, to assess the effect on pain in these patients in comparison with those without central nervous system disease. DESIGN: Retrospective study in which pain, mood, and sensory function in 32 patients with chronic pain who had mild Chiari I malformation were compared with that in 53 patients with chronic pain who had moderate to severe compression of the cervical spinal cord and 52 patients with chronic pain who had no apparent central nervous system disorder. Data had been collected previously as part of standard clinical assessments, including clinical neurological examinations, quantitative sensory testing, pain drawings, and psychometric testing with the Symptom Checklist 90. PATIENTS: All subjects were patients of a hospital-based pain management practice who had been accepted for treatment over a 5-year period. RESULTS: Both the Chiari I and cervical compression groups had long tract signs evident on clinical neurological examination. Quantitative sensory testing indicated elevations in the trigeminal territory among patients with Chiari I malformation and on the neck, hands, and feet in both the Chiari I and cervical compression groups. The extent of pain and mood disturbance was greatest in the Chiari I group and least in the group with no central nervous system disorder. Complex regional pain syndrome, fibromyalgia, and temporal mandibular joint disorder were more common among the Chiari I malformation group than among the other groups. CONCLUSIONS: Quantitative sensory analysis indicates sensory dysfunction associated with Chiari I malformation and cervical cord compression. The pattern of sensory abnormality is consistent with medullary dysfunction among the patients with Chiari I malformation and cervical cord dysfunction among cord compression patients. There were differences in the types and extent of pain and the associated disorders of mood observed among the cohorts defined above. These differences may be partly due to the presence and location of central sensory dysfunction.

Adult↗

PubMed1997

Gabexate mesilate, a synthetic protease inhibitor, prevents compression-induced spinal cord injury by inhibiting activation of leukocytes in rats.

OBJECTIVE: Gabexate mesilate is a synthetic protease inhibitor capable of inhibiting both coagulation and cytokine production by monocytes. To investigate whether gabexate mesilate is useful for the prevention of posttraumatic spinal cord injury, we examined its effect on compression trauma-induced spinal cord injury in rats. DESIGN: Prospective, randomized, blinded, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats weighing 300 to 350 g. INTERVENTIONS: Spinal cord injury was induced by applying a 20-g weight extradurally to the spinal cord at the level of the 12th thoracic vertebra for 20 mins. Spinal cord injury was evaluated by assessing the motor function of the rats 24 hrs posttrauma. The accumulation of leukocytes and histologic changes in the injured spinal cord tissue also were examined. Rats received gabexate mesilate (10 or 20 mg/kg i.p.) 30 mins before or after the compressive trauma. The effects of heparin or an inactive derivative of activated factor X (a selective inhibitor of thrombin generation) on compressive trauma-induced spinal cord injury also were examined. Leukocytopenia was induced by the administration of nitrogen mustard. MEASUREMENTS AND MAIN RESULTS: The motor disturbances observed following traumatic spinal cord compression, evaluated by Tarlov's score, and the accumulation of leukocytes in the injured tissue, evaluated by measuring tissue myeloperoxidase activity, were markedly reduced by leukocyte depletion induced by nitrogen mustard and by pre- or posttreatment of animals with gabexate mesilate. Neither heparin nor the inactive derivative of activated factor X prevented the motor disturbances and the accumulation of leukocytes. Histologic examination demonstrated that intramedullary hemorrhages observed 24 hrs after trauma at the 12th thoracic vertebra were significantly attenuated by nitrogen mustard-induced leukocytopenia and the administration of gabexate mesilate. CONCLUSIONS: The compression trauma-induced spinal cord injury demonstrated by this model was mainly mediated by leukocytes. Gabexate mesilate prevented spinal cord injury not by inhibiting coagulation, but by inhibiting the activation of leukocytes.

Amino Acid Chloromethyl Ketones↗

PubMed1996

Acute median nerve compression at the distal forearm caused by a thrombosed aneurysm of an epineural vessel: case report.

The case of a patient with a 2-day history of symptoms suggesting acute carpal tunnel syndrome is presented. However, an urgent electroneurographic examination revealed median nerve compression at the forearm and magnetic resonance imaging confirmed compression by a mass proximal to the carpal tunnel. Surgical exploration showed a recently thrombosed aneurysm of an epineural vessel. Histological and, later, general and angiological investigations could not reveal the underlying cause of this aneurysm. Preoperative electrodiagnostic examination is recommended in acute peripheral nerve compression to prevent decompression at an incorrect site. If atypical nerve compression is suspected, magnetic resonance imaging may be indicated to detect localized nerve compression and its underlying cause.

Adult↗

PubMed2000

Spasmodic torticollis due to neurovascular compression of the spinal accessory nerve by the anteroinferior cerebellar artery: case report.

OBJECTIVE AND IMPORTANCE: Spasmodic torticollis is a neuromuscular disorder characterized by uncontrollable clonic and intermittently tonic spasm of the neck muscles. We report a case of spasmodic torticollis attributable to neurovascular compression of the right XIth cranial nerve by the right anteroinferior cerebellar artery (AICA). CLINICAL PRESENTATION: A 72-year-old man with a 2-year history of right spasmodic torticollis underwent magnetic resonance imaging, which demonstrated compression of the right XIth cranial nerve by an abnormal descending loop of the right AICA. INTERVENTION: The patient underwent microvascular decompression surgery. During surgery, it was confirmed that an abnormal loop of the right AICA was compressing the right accessory nerve. Compression was released by the interposition of muscle between the artery and the nerve. CONCLUSION: The patient's postoperative course was uneventful, and his symptoms were fully relieved at the 2-year follow-up examination. This is the first reported case of spasmodic torticollis attributable to compression by the AICA; usually, the blood vessels involved are the vertebral artery and the posteroinferior cerebellar artery.

Accessory Nerve Diseases↗

PubMedDate not supplied

Osteophytes of the spine compressing the sympathetic trunk and splanchnic nerves in the thorax.

The presence of osteophytes compressing the sympathetic structures in the thorax was found in 655 (65.5%) of 1,000 cadavers. In 60.4% of the affected cases, the compression was on the right side, and in 36.9% it was bilateral, although the right side was more severely affected. In 2%, the compression was on the left only. The highest frequency of compression was at the T8-10 level, the right greater splanchnic nerve being the structure most frequently involved. The sympathetic trunk itself (ganglia and cord) was affected only by osteophytes of vertebrae at the lowest thoracic levels; however, bony excrescences due to costovertebral joint arthritis were frequently found impinging on the sympathetic trunk and its rami communicantes at similar frequencies on both sides. The factors governing the characteristic compression of the sympathetic structures in the thorax are the typical development of the osteophytes and the special relations of the sympathetic structures to the vertebral column at the various levels. It is proposed that these observations are useful in understanding certain observed clinical conditions and act an anatomic baseline for research in the future.

Aged↗

PubMed1991

Changes in the evoked spinal cord potentials associated with chronic experimental cord compression.

To determine the functional changes occurring in the early period after the development of chronic cord compression, an ossification of the ligamentum flavum model, which is a model of chronic cord compression, was created in domestic rabbits using bone morphogenetic protein, and monitored evoked spinal cord potentials. Sixty-seven rabbits were used for these experiments. Myelography, evoked spinal cord potential measurements, and histologic examinations were performed in 16 of the ossification of the ligamentum flavum rabbits and six of the healthy control rabbits. Our results show that 1) mild degrees of cord compression produce greater evoked spinal cord potential alterations in chronic than in acute compression, as reported in the literature; 2) chronic compression from the dorsal side produces injury in the superficial layer of the dorsal column and dorsolateral column; and 3) changes in evoked spinal cord potentials precede the development of paralysis and histologic changes.

Animals↗

PubMed1992

Morphologic and quantitative changes in neurotransmitters in the lumbar spinal cord after acute or chronic mechanical compression of the cauda equina.

Changes in the neurotransmitters associated with pain transmission and regulation in the lumbar spinal cord were studied after acute or chronic mechanical compression of the cauda equina in rats. Using glyoxylic acid histofluorescence and immunohistochemical methods, it was morphologically apparent that substance P-containing nerve ending were decreased after chronic compression of the cauda equina. Somatostatin nerve terminals were reduced, and aminergic fibers and serotonin were enhanced after both acute and chronic mechanical compressions. In addition, quantitative analysis revealed that the levels of norepinephrine and serotonin remained elevated after mechanical compression of the cauda equina. It is suggested that pain in the lower back and extremities after mechanical compression of the cauda equina is controlled by these complicated changes of neurotransmitters in the lumbar spinal cord.

Animals↗

PubMed1992

Local electrophysiologic stimulation in experimental double level cauda equina compression.

Double level compression of nerve roots has been known to exist for a long time, but only in recent years the clinical significance of such conditions has been discussed. In the current study, nerve root function in double level compression was analyzed by measurements of tail muscle electromyogram, after stimulations of 1) the intermediate segment between the compression sites and 2) cranial to the two compression sites in a pig model. The electromyogram-amplitudes were more reduced after intermediate, than cranial stimulation. This difference was suggested to be based on an additional increasing threshold to elicit an action potential within the intermediate segment due to a nutritional deficit at this location. The results further stress the importance of local changes within the intermediate segment in double level nerve root compression.

Action Potentials↗

PubMed1995

Production of chronic compression of the cauda equina in rats for use in studies of lumbar spinal canal stenosis.

STUDY DESIGN: The pathophysiology of lumbar spinal canal stenosis was analyzed with a new model in rats. OBJECTIVES: To produce chronic compression of the cauda equina in rats for analysis of the pathophysiology of lumbar spinal canal stenosis. SUMMARY OF BACKGROUND DATA: Models of compression to date have involved acute or subacute compression. A model of chronic compression has not been available. METHODS: A stainless steel wire fastened around the spine at L5 in 3-week-old rats, with a plate inserted against the ventral aspect of the vertebra to protect it from the wire. as the rats grew, the wire cut into the spinal canal. One year after the operation, canal stenosis was present without paralysis of the back limbs. RESULTS: Stenosis seen in sagittal sections, as a percentage of the original width, was 51.6 +/- 6.2% (mean +/- standard deviation). In histologic analysis of the region near the wire, findings included axonal degeneration, demyelination, vacuolar degeneration of the nerve fibers, and narrowing the intradural blood vessels with a decrease in their number. Cephalad and caudad to the wire, congested intradural blood vessels, degenerative foci near these congested vessels, fibrosis around these foci, congested epidural vessels, and fibrosis around these vessels were observed. During electrophysiologic analysis (six rats with stenosis), the conduction velocity of the cauda equina was found to be delayed. CONCLUSIONS: The histologic and electrophysiologic findings in this animal model were similar to findings in human subjects, so rats prepared in this way should be useful for study of chronic compression of the cauda equina.

Animals↗

PubMed1996

Amyloidosis-related cauda equina compression in long-term hemodialysis patients. Three case reports.

STUDY DESIGN: These case reports illustrate the neurologic manifestations due to beta 2 microglobulin amyloid deposition at the lumbar spine level in long-term hemodialysis patients. OBJECTIVE: Radiologic investigations suggested the amyloid origin of extradural soft tissue deposition, which was confirmed by histologic examination after surgical excision. SUMMARY OF BACKGROUND DATA: Although cervical myelopathy is a recently recognized complication of long-term dialysis-related beta 2 microglobulin amyloidosis, neurologic manifestations due to amyloid deposition at the lumbar spine level have rarely been reported. METHODS: Three case reports of cauda equina compression in long-term hemodialysis patients are presented. Follow-up radiography, computed tomography, and magnetic resonance imaging were performed and patients underwent surgical decompression of the thecal sac. RESULTS: In two patients, the compression resulted from the development of a destructive spondylarthropathy, and from the infiltration of extradural spaces and ligaments by an abnormal soft tissue. The third patient had lumbar spinal stenosis due to multiple disc protrusion and to hypertrophy of facet joints and ligamentum flavum. Multilevel laminectomies enabled excision of an abnormal fibrous tissue responsible for the thecal sac compression. Histologic examination of the excised fibrous tissues disclosed amyloid deposits in intervertebral discs, apophysial joints, and ligaments. CONCLUSIONS: In long-term hemodialysis patients, cauda equina compression may develop as the consequence of beta 2 microglobulin amyloid deposition in lumbar intervertebral discs, facet joints, and ligaments. Magnetic resonance imaging is well suited to show the extent of the compression and supports the argument for the amyloid origin of extradural soft tissue.

Adult↗

PubMed1996

The effects of mechanical compression and hypoxia on nerve root and dorsal root ganglia. An analysis of ectopic firing using an in vitro model.

STUDY DESIGN: This study analyzed in vitro experiments of ectopic firing evoked by mechanical compression or hypoxia of canine lumbar dorsal roots with dorsal root ganglia using an in vitro model. OBJECTIVES: The results were correlated to understand the pathophysiology of radiculopathy, which manifests abnormal sensation and pain. SUMMARY OF BACKGROUND DATA: It has been speculated that blood flow in the nerve root and mechanical compression play major roles in the production of radiculopathy symptoms. However, no precise experimental studies have been conducted on the relationship between these factors and the development of ectopic firing. METHODS: Canine lumbar dorsal roots with dorsal root ganglia were immersed in an oxygenated artificial cerebrospinal fluid, and activity of the nerve root was recorded using bipolar platinum electrodes. Using this model, the effects of quantitative mechanical compression and hypoxia on the ectopic firing were analyzed. RESULTS: When compression was applied, mechanical thresholds for eliciting firing were much lower in dorsal root ganglia than in dorsal roots, and the firing lasted for a longer period in dorsal root ganglia. Under hypoxia, dorsal root ganglia showed firing, and their thresholds from mechanical stimuli decreased significantly. In dorsal roots, impulse propagation was not affected, whereas firing was seen under the hypoxic condition. CONCLUSION: Dorsal root ganglia are highly sensitive to mechanical compression and hypoxia and closely related to abnormal sensations and pain in radiculopathy.

Action Potentials↗

PubMed1998

Lumbar spinal root compression caused by Brucella granuloma.

STUDY DESIGN: A case report of rarely seen extradural brucellosis granuloma causing spinal root compression in the lumbar region. OBJECTIVE: To point out the possibility of extradural compression caused by brucellosis. SUMMARY OF BACKGROUND DATA: Many investigators have indicated that myelopathy or radiculopathy caused by irritation or compression by tiny abscess, disc herniation, or extradural granuloma may occur in brucellosis. Failure to make the correct diagnosis is possible because of the absence of such symptoms of brucellosis as fever, sweating, or fatigue and because findings of physical examination, radiography, and myelography indicate intervertebral disc herniation. METHODS: Review and discussion of the case history are presented. RESULTS: Brucella granuloma compressing the right L5 root and dural sac was diagnosed on computed tomographic scans and was excised subtotally after laminectomy and facetectomy. CONCLUSION: The possibility of extradural compression caused by brucellosis should be considered in endemic areas and must be differentiated from an intervertebral disc herniation by means of agglutination testing and bone scan.

Brucellosis↗